The 2002 Official Patient's Sourcebook on Angina

THE 2002 OFFICIAL PATIENT’S SOURCEBOOK

on

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The 2002 Official Patient’s Sourcebook on Angina: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83135-1 1. Angina-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

iv

Dedication To the healthcare professionals dedicating their time and efforts to the study of angina.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to the study of angina. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

vi

About ICON Health Publications In addition to angina, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Angina

·

The Official Patient's Sourcebook on Arrhythmia

·

The Official Patient's Sourcebook on Coronary Heart Disease

·

The Official Patient's Sourcebook on Dilated Cardiomyopathy

·

The Official Patient's Sourcebook on Heart Failure

·

The Official Patient's Sourcebook on Hypertrophic Cardiomyopathy

·

The Official Patient's Sourcebook on Restrictive Cardiomyopathy

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON ANGINA: GUIDELINES .................... 9

Overview............................................................................................................... 9 What Is Angina? ................................................................................................ 11 What Brings on Angina? ................................................................................... 11 How Is Angina Diagnosed? ............................................................................... 12 How Is Angina Treated? .................................................................................... 13 What Is the Difference between “Stable” and “Unstable” Angina?.................. 15 Are There Other Types of Angina? .................................................................... 15 Additional Resources .......................................................................................... 16 More Guideline Sources ..................................................................................... 16 Vocabulary Builder............................................................................................. 24

CHAPTER 2. SEEKING GUIDANCE ....................................................... 27

Overview............................................................................................................. 27 Associations and Angina.................................................................................... 27 Finding Doctors.................................................................................................. 29 Selecting Your Doctor ........................................................................................ 31 Working with Your Doctor ................................................................................ 31 Broader Health-Related Resources ..................................................................... 33

CHAPTER 3. CLINICAL TRIALS AND ANGINA..................................... 35

Overview............................................................................................................. 35 Recent Trials on Angina..................................................................................... 38 Benefits and Risks............................................................................................... 42 Keeping Current on Clinical Trials.................................................................... 45 General References.............................................................................................. 46 Vocabulary Builder............................................................................................. 47

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 51 CHAPTER 4. STUDIES ON ANGINA ...................................................... 53

Overview............................................................................................................. 53 The Combined Health Information Database ..................................................... 53 Federally-Funded Research on Angina .............................................................. 56 E-Journals: PubMed Central .............................................................................. 62 The National Library of Medicine: PubMed ...................................................... 63

viii Contents

Vocabulary Builder............................................................................................. 71

CHAPTER 5. PATENTS ON ANGINA ..................................................... 79

Overview............................................................................................................. 79 Patents on Angina .............................................................................................. 80 Patent Applications on Angina .......................................................................... 89 Keeping Current ................................................................................................. 91 Vocabulary Builder............................................................................................. 91

CHAPTER 6. BOOKS ON ANGINA ........................................................ 95

Overview............................................................................................................. 95 Book Summaries: Federal Agencies .................................................................... 95 Book Summaries: Online Booksellers ................................................................. 97 The National Library of Medicine Book Index ................................................... 98 Chapters on Angina.......................................................................................... 101 General Home References ................................................................................. 105 Vocabulary Builder........................................................................................... 106

CHAPTER 7. MULTIMEDIA ON ANGINA............................................ 109

Overview........................................................................................................... 109 Bibliography: Multimedia on Angina .............................................................. 109

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ................... 113

Overview........................................................................................................... 113 NIH Guidelines................................................................................................. 113 NIH Databases.................................................................................................. 118 Other Commercial Databases ........................................................................... 122 The Genome Project and Angina...................................................................... 123 Specialized References....................................................................................... 128 Vocabulary Builder........................................................................................... 128

CHAPTER 9. DISSERTATIONS ON ANGINA ........................................ 131

Overview........................................................................................................... 131 Dissertations on Angina................................................................................... 131 Keeping Current ............................................................................................... 132

PART III. APPENDICES .................................................. 133 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 135

Overview........................................................................................................... 135 Your Medications: The Basics .......................................................................... 136 Learning More about Your Medications .......................................................... 137 Commercial Databases...................................................................................... 140 Contraindications and Interactions (Hidden Dangers) ................................... 146 A Final Warning .............................................................................................. 147 General References............................................................................................ 147 Vocabulary Builder........................................................................................... 148

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 151

Overview........................................................................................................... 151

Contents

ix

What Is CAM? ................................................................................................. 151 What Are the Domains of Alternative Medicine?............................................ 152 Can Alternatives Affect My Treatment? ......................................................... 155 Finding CAM References on Angina ............................................................... 156 Additional Web Resources................................................................................ 167 General References............................................................................................ 167

APPENDIX C. RESEARCHING NUTRITION ......................................... 187

Overview........................................................................................................... 187 Food and Nutrition: General Principles........................................................... 188 Finding Studies on Angina .............................................................................. 192 Federal Resources on Nutrition........................................................................ 196 Additional Web Resources................................................................................ 197 Vocabulary Builder........................................................................................... 204

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 207

Overview........................................................................................................... 207 Preparation ....................................................................................................... 207 Finding a Local Medical Library ...................................................................... 208 Medical Libraries Open to the Public............................................................... 208

APPENDIX E. TRIGLYCERIDE, HIGH DENSITY LIPOPROTEIN, AND CORONARY HEART DISEASE ............................................................. 217

Overview........................................................................................................... 217 Abstract ............................................................................................................ 218 What Is Triglyceride, High Density Lipoprotein? ........................................... 219 Causal Relationship: Triglyceride, HDL, and Coronary Heart Disease .......... 221 Prevention of Coronary Heart Disease............................................................. 224 Should Triglyceride and HDL Be Measured? .................................................. 226 Dietary, Drug, and Other Hygienic Treatments ............................................. 227 High-Risk Individuals and the General Population ......................................... 231 High Triglyceride or Low HDL-C and Cardiovascular Disease Risk .............. 231 Questions for Continuing Research ................................................................. 233 Conclusions....................................................................................................... 234

APPENDIX F. LOWERING BLOOD CHOLESTEROL .............................. 237

Overview........................................................................................................... 237 What Is Coronary Heart Disease?.................................................................... 238 Causal Relationship: Blood Cholesterol Levels and Coronary Heart Disease .. 241 Prevention of Coronary Heart Disease?........................................................... 243 Should Dietary or Drug Treatment.................................................................. 245 Reducing the Blood Cholesterol of the General Population.............................. 251 Research Directions .......................................................................................... 253

APPENDIX G. PHYSICAL ACTIVITY ................................................... 257

Overview........................................................................................................... 257 Abstract ............................................................................................................ 258 Causes and Risk Factors ................................................................................... 259 Sedentary Lifestyle............................................................................................ 261

x

Contents

Prevention......................................................................................................... 263 Benefits and Risks of Different Types of Physical Activity.............................. 265 Successful Approaches...................................................................................... 267 Future Research ................................................................................................ 269 Conclusions....................................................................................................... 270

ONLINE GLOSSARIES.................................................... 273 Online Dictionary Directories.......................................................................... 277

ANGINA GLOSSARY ...................................................... 279 General Dictionaries and Glossaries ................................................................ 303

INDEX................................................................................... 305

Introduction

1

INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Angina

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Angina has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to angina, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on angina. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on angina should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate options is always up to the patient in consultation with their physician and healthcare providers.

Introduction

3

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching angina (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to angina. It also gives you sources of information that can help you find a doctor in your local area specializing in diagnosing and treating angina. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with angina. Part II moves on to advanced research dedicated to angina. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on angina. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “freeto-use” options. Part III provides appendices of useful background reading for all patients with angina or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with angina. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with angina.

Scope While this sourcebook covers angina, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that angina is often considered a synonym or a condition closely related to the following: ·

Angina Pectoris

·

Heberden's Syndrome

·

StenocardiaAngina Pectoris

·

Heberden's Syndrome

·

Stenocardia

4

Angina

In addition to synonyms and related conditions, physicians may refer to angina using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for angina:4 ·

411.1 angina, stable

·

413 angina pectoris

·

413.1 prinzmetal's angina

·

413.9 angina, unspecified

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to angina. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses and conditions. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients with angina will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

5

wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with angina is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of angina, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

7

PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on angina. The essentials of a symptom typically include the definition or description of the symptom, a discussion of who it affects, the diseases that are associated with a given symptom, tests or diagnostic procedures that might be specific to the symptom, and treatments for the symptom. Your doctor or healthcare provider may have already explained the essentials of angina to you or even given you a pamphlet or brochure describing angina. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

9

CHAPTER 1. THE ESSENTIALS ON ANGINA: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on angina. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on angina can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on angina. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Angina

There is no guarantee that any one Institute will have a guideline on a specific condition or disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare conditions and disorders. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with angina and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines at http://www.nhlbi.nih.gov/guidelines/index.htm

Among these, the National Heart, Lung, and Blood Institute (NHLBI) is particularly noteworthy. The NHLBI provides leadership for a national program in diseases of the heart, blood vessels, lung, and blood; blood resources; and sleep disorders.6 Since October 1997, the NHLBI has also had administrative responsibility for the NIH Woman’s Health Initiative. The Institute plans, conducts, fosters, and supports an integrated and coordinated program of basic research, clinical investigations and trials, observational studies, and demonstration and education projects. Research is related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The NHLBI plans and directs research in development and evaluation of interventions and devices related to prevention, treatment, and rehabilitation of patients suffering from such diseases and disorders. It also supports research on clinical use of blood and all aspects of the management of blood resources. Research is conducted in the Institute’s own laboratories and by scientific institutions and individuals supported by research grants and contracts. For health professionals and the public, the NHLBI conducts educational activities, including development and dissemination of materials in the above areas, with an emphasis on prevention. Within the NHLBI, the Division of Heart and Vascular Diseases (DHVD) plans and directs the NHLBI’s research grant, contract, and training This paragraph has been adapted from the NHLBI: http://www.nhlbi.nih.gov/about/org/mission.htm. “Adapted” signifies that a passage is reproduced exactly or slightly edited for this book. 6

Guidelines 11

programs in heart and vascular diseases.7 These programs encompass institute- and investigator-initiated basic research, targeted research, specialized centers and clinical trials. The DHVD maintains surveillance over developments in its program areas and assesses the national need for research on the causes, prevention, diagnosis, and treatment of cardiovascular disease. The DHVD ensures that effective new techniques, treatments and strategies resulting from medical research are transferred to the community through professional, patient, and public education programs in a timely manner. The following patient guideline was recently published by the NHLBI and the DHVD on angina.

What Is Angina?8 Angina pectoris (“angina”) is a recurring pain or discomfort in the chest that happens when some part of the heart does not receive enough blood. It is a common symptom of coronary heart disease (CHD), which occurs when vessels that carry blood to the heart become narrowed and blocked due to atherosclerosis Angina feels like a pressing or squeezing pain, usually in the chest under the breast bone, but sometimes in the shoulders, arms, neck, jaws, or back. Angina is usually precipitated by exertion. It is usually relieved within a few minutes by resting or by taking prescribed angina medicine.

What Brings on Angina? Episodes of angina occur when the heart’s need for oxygen increases beyond the oxygen available from the blood nourishing the heart. Physical exertion is the most common trigger for angina. Other triggers can be emotional stress, extreme cold or heat, heavy meals, alcohol, and cigarette smoking.

Does Angina Mean a Heart Attack Is About to Happen? An episode of angina is not a heart attack. Angina pain means that some of the heart muscle in not getting enough blood temporarily--for example, 7 This paragraph has been adapted from the DHVD: http://www.nhlbi.nih.gov/about/dhvd/index.htm. For more information, contact: Division of Heart and Vascular Diseases; National Heart, Lung, and Blood Institute; Two Rockledge Center - Suite 9160; 6701 Rockledge Dr. - MSC 7940; Bethesda, MD 20892-7940. 8 Adapted from the National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/public/heart/other/angina.htm.

12 Angina

during exercise, when the heart has to work harder. The pain does NOT mean that the heart muscle is suffering irreversible, permanent damage. Episodes of angina seldom cause permanent damage to heart muscle. In contrast, a heart attack occurs when the blood flow to a part of the heart is suddenly and permanently cut off. This causes permanent damage to the heart muscle. Typically, the chest pain is more severe, lasts longer, and does not go away with rest or with medicine that was previously effective. It may be accompanied by indigestion, nausea, weakness, and sweating. However, the symptoms of a heart attack are varied and may be considerably milder. When someone has a repeating but stable pattern of angina, an episode of angina does not mean that a heart attack is about to happen. Angina means that there is underlying coronary heart disease. Patients with angina are at an increased risk of heart attack compared with those who have no symptoms of cardiovascular disease, but the episode of angina is not a signal that a heart attack is about to happen. In contrast, when the pattern of angina changes--if episodes become more frequent, last longer, or occur without exercise--the risk of heart attack in subsequent days or weeks is much higher. A person who has angina should learn the pattern of his or her angina--what cause an angina attack, what it feels like, how long episodes usually last, and whether medication relieves the attack. If the pattern changes sharply or if the symptoms are those of a heart attack, one should get medical help immediately, perhaps best done by seeking an evaluation at a nearby hospital emergency room. Is All Chest Pain “Angina?” No, not at all. Not all chest pain is from the heart, and not all pain from the heart is angina. For example, if the pain lasts for less that 30 seconds or if it goes away during a deep breath, after drinking a glass of water, or by changing position, it almost certainly is NOT angina and should not cause concern. But prolonged pain, unrelieved by rest and accompanied by other symptoms may signal a heart attack.

How Is Angina Diagnosed? Usually the doctor can diagnose angina by noting the symptoms and how they arise. However one or more diagnostic tests may be needed to exclude angina or to establish the severity of the underlying coronary disease. These

Guidelines 13

include the electrocardiogram (ECG) at rest, the stress test, and x- rays of the coronary arteries (coronary “arteriogram” or “angiogram”). The ECG records electrical impulses of the heart. These may indicate that the heart muscle is not getting as much oxygen as it needs (“ischemia”); they may also indicate abnormalities in heart rhythm or some of the other possible abnormal features of the heart. To record the ECG, a technician positions a number of small contacts on the patient’s arms, legs, and across the chest to connect them to an ECG machine. For many patients with angina, the ECG at rest is normal. This is not surprising because the symptoms of angina occur during stress. Therefore, the functioning of the heart may be tested under stress, typically exercise. In the simplest stress test, the ECG is taken before, during, and after exercise to look for stress related abnormalities. Blood pressure is also measured during the stress test and symptoms are noted. A more complex stress test involves picturing the blood flow pattern in the heart muscle during peak exercise and after rest. A tiny amount of a radioisotope, usually thallium, is injected into a vein at peak exercise and is taken up by normal heart muscle. A radioactivity detector and computer record the pattern of radioactivity distribution to various parts of the heart muscle. Regional differences in radioisotope concentration and in the rates at which the radioisotopes disappear are measures of unequal blood flow due to coronary artery narrowing, or due to failure of uptake in scarred heart muscle. The most accurate way to assess the presence and severity of coronary disease is a coronary angiogram, an x-ray of the coronary artery. A long thin flexible tube (a “catheter”) is threaded into an artery in the groin or forearm and advanced through the arterial system into one of the two major coronary arteries. A fluid that blocks x-rays (a “contrast medium” or “dye”) is injected. X-rays of its distribution show the coronary arteries and their narrowing.

How Is Angina Treated? The underlying coronary artery disease that causes angina should be attacked by controlling existing “risk factors.” These include high blood pressure, cigarette smoking, high blood cholesterol levels, and excess weight. If the doctor has prescribed a drug to lower blood pressure, it should be taken as directed. Advice is available on how to eat to control weight, blood

14 Angina

cholesterol levels, and blood pressure. A physician can also help patients to stop smoking. Taking these steps reduces the likelihood that coronary artery disease will lead to a heart attack. Most people with angina learn to adjust their lives to minimize episodes of angina, by taking sensible precautions and using medications if necessary. Usually the first line of defense involves changing one’s living habits to avoid bringing on attacks of angina. Controlling physical activity, adopting good eating habits, moderating alcohol consumption, and not smoking are some of the precautions that can help patients live more comfortably and with less angina. For example, if angina comes on with strenuous exercise, exercise a little less strenuously, but do exercise. If angina occurs after heavy meals, avoid large meals and rich foods that leave one feeling stuffed. Controlling weight, reducing the amount of fat in the diet, and avoiding emotional upsets may also help. Angina is often controlled by drugs. The most commonly prescribed drug for angina is nitroglycerin, which relieves pain by widening blood vessels. This allows more blood to flow to the heart muscle and also decreases the work load of the heart. Nitroglycerin is taken when discomfort occurs or is expected. Doctors frequently prescribe other drugs, to be taken regularly, that reduce the heart’s workload. Beta blockers slow the heart rate and lessen the force of the heart muscle contraction. Calcium channel blockers are also effective in reducing the frequency and severity of angina attacks.

What If Medication Fails to Control Angina? Doctors may recommend surgery or angioplasty if drugs fail to ease angina or if the risk of heart attack is high. Coronary artery bypass surgery is an operation in which a blood vessel is grafted onto the blocked artery to bypass the blocked or diseased section so that blood can get to the heart muscle. An artery from inside the chest (an “internal mammary” graft) or long vein from the leg (a “saphenous vein” graft) may be used. Balloon angioplasty involves inserting a catheter with a tiny balloon at the end into a forearm or groin artery. The balloon is inflated briefly to open the vessel in places where the artery is narrowed. Other catheter techniques are also being developed for opening narrowed coronary arteries, including laser and mechanical devices applied by means of catheters.

Guidelines 15

Can a Person with Angina Exercise? Yes. It is important to work with the doctor to develop an exercise plan. Exercise may increase the level of pain-free activity, relieve stress, improve the heart’s blood supply, and help control weight. A person with angina should start an exercise program only with the doctor’s advice. Many doctors tell angina patients to gradually build up their fitness level--for example, start with a 5-minute walk and increase over weeks or months to 30 minutes or 1 hour. The idea is to gradually increase stamina by working at a steady pace, but avoiding sudden bursts of effort.

What Is the Difference between “Stable” and “Unstable” Angina? It is important to distinguish between the typical stable pattern of angina and “unstable” angina. Angina pectoris often recurs in a regular or characteristic pattern. Commonly a person recognizes that he or she is having angina only after several episodes have occurred, and a pattern has evolved. The level of activity or stress that provokes the angina is somewhat predictable, and the pattern changes only slowly. This is “stable” angina, the most common variety. Instead of appearing gradually, angina may first appear as a very severe episode or as frequently recurring bouts of angina. Or, an established stable pattern of angina may change sharply; it may by provoked by far less exercise than in the past, or it may appear at rest. Angina in these forms is referred to as “unstable angina” and needs prompt medical attention. The term “unstable angina” is also used when symptoms suggest a heart attack but hospital tests do not support that diagnosis. For example, a patient may have typical but prolonged chest pain and poor response to rest and medication, but there is no evidence of heart muscle damage either on the electrocardiogram or in blood enzyme tests.

Are There Other Types of Angina? There are two other forms of angina pectoris. One, long recognized but quite rare, is called Prinzmetal’s or variant angina. This type is caused by vasospasm, a spasm that narrows the coronary artery and lessens the flow of blood to the heart. The other is a recently discovered type of angina called

16 Angina

microvascular angina. Patients with this condition experience chest pain but have no apparent coronary artery blockages. Doctors have found that the pain results from poor function of tiny blood vessels nourishing the heart as well as the arms and legs. Microvascular angina can be treated with some of the same medications used for angina pectoris.

Additional Resources ·

Facts About Blood Cholesterol (revised 1994), NIH Publication No. 942696

·

Fact About Coronary Heart Disease (reprinted 1993), NIH Publication No. 93-2265

·

Facts About Heart Failure (reprinted 1995) NIH Publication No. 95-923

·

Facts About Heart Disease and Women: So You Have Heart Disease, NIH Publication No. 95-2645

·

High Blood Pressure and What You Can Do About It, NIH Publication No. 55-222A

·

So You Have High Blood Cholesterol (revised 1993), NIH Publication No. 93-2922

·

Step by Step: Eating to Lower Your High Blood Cholesterol (revised 1994) NIH Publication No. 94-2920

For further information, call or write: National Heart, Lung, and Blood Institute Information Office P.O. Box 30105 Bethesda, MD 20892-0105 Telephone: (301) 592-8573

More Guideline Sources The guideline above on angina is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to angina. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with angina. Due to space limitations these sources are listed in a concise manner. Do not

Guidelines 17

hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following as being relevant to angina: ·

Guides On angina Angina http://www.nlm.nih.gov/medlineplus/ency/article/001107.htm Angina http://www.nlm.nih.gov/medlineplus/angina.html

·

Other Guides Unstable angina http://www.nlm.nih.gov/medlineplus/ency/article/000201.htm Stable angina http://www.nlm.nih.gov/medlineplus/ency/article/000198.htm Ludwig's angina http://www.nlm.nih.gov/medlineplus/ency/article/001047.htm Coronary artery spasm http://www.nlm.nih.gov/medlineplus/ency/article/000159.htm

Within the health topic page dedicated to angina, the following was recently recommended to patients:

18 Angina

·

General/Overviews Angina http://www.nlm.nih.gov/medlineplus/tutorials/anginaloader.html Angina Pectoris Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4472

·

Diagnosis/Symptoms CK-MB Test Source: American Association for Clinical Chemistry http://labtestsonline.org/understanding/analytes/ckmb/glance.html Coronary Angiography Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=11222 Echocardiography Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HB00012

·

Treatment Angina Pectoris Treatments Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4496 External Counterpulsation Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4577 Transmyocardial Revascularization (TMR) Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4782

·

Specific Conditions/Aspects Angina and Heart Disease Source: American Academy of Family Physicians http://familydoctor.org/handouts/233.html Syndrome X Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=534

Guidelines 19

·

From the National Institutes of Health Facts About Angina Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/heart/other/angina.htm

·

Latest News Five-Week Antibiotic Treatment May Improve Cardiovascular Function Source: 02/26/2002, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3000957 Have You Had a Heart Attack or Been Diagnosed With Heart Failure, Angina or Heart Disease? Find Your Best Treatment Option With New Online Tool. Source: 05/06/2002, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3002595 Self-management Plan Helps Chest Pain Patients Source: 04/18/2002, Reuters Health http://www.nlm.nih.gov/medlineplus/news/fullstory_7204.html Three-Month Antibiotic Treatment Reduces Risk of Future Heart Attack Source: 03/13/2002, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3001179

·

Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/index.htm

·

Research Five-Week Antibiotic Treatment May Improve Cardiovascular Function Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3000957 Gene Therapy to Treat Angina Appears Safe Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3000956

20 Angina

Hormone Replacement For Men Eases Chest Pain From Heart Disease Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=2933 Medicine-coated Stent May Limit Artery Re-clogging, Repeat Procedures Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3113 ·

Statistics 2002 Heart and Stroke Statistical Update Source: img src='/medlineplus/images/linkpdf.gif' width='100' height='17' border=0 alt='Links to PDF File'> (American Heart Association http://www.americanheart.org/downloadable/heart/1014832809466 1013190990123HS_State_02.pdf Heart Attack and Angina Statistics Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4591

·

Women

Angina Source: National Women's Health Information Center http://www.4woman.gov/faq/angina.htm?src=ng If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on angina and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To

Guidelines 21

search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

My Healthy Heart Source: Minneapolis, MN: International Diabetes Center. 1997. 4 p. Contact: Available from Park Nicollet Health Source. 3800 Park Nicollet Boulevard, Minneapolis, MN 55416. (800) 372-7776 or (612) 993-3534. Fax (612) 993-1840. PRICE: $1.25 each for 10-49 copies; $1.12 each for 50-99 copies; $1.03 each for 100-499 copies. ISBN: 188511544X. Summary: This brochure provides people who have diabetes with information about caring for their hearts. The brochure points out that heart disease is the direct cause of 55 percent of deaths among people with diabetes. Although chest pain (angina), heart attack, and congestive heart failure often seem to appear suddenly, they are almost always the result of years of slow damage to the blood vessels and heart. The brochure advises readers to review their blood glucose control and blood pressure at each visit with a health care professional. The brochure includes a description and a target value for each of the following necessary tests: HbA1c, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and blood pressure. The risk of heart disease can be reduced by controlling blood glucose, refraining from smoking, eating a diet low in saturated fat, getting regular exercise, and balancing stress. If lifestyle changes alone are insufficient, it may be necessary to take medications which help to lower cholesterol and blood pressure. Two sidebars provide space for recording test results and a list of medications and their functions. The brochure also includes a questionnaire designed to assess risk. (AA-M). The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “angina” or synonyms. The following was recently posted:

22 Angina

·

ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Source: American College of Cardiology/American Heart Association.; 2000; 93 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1800&sSearch_string=angina

·

Angina pectoris and coronary heart disease (CHD). Source: Finnish Medical Society Duodecim.; 2001 April 30; Various pagings http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1839&sSearch_string=angina

·

Coronary revascularisation in the management of stable angina pectoris. A national clinical guideline. Source: Scottish Intercollegiate Guidelines Network.; 1998 November; 42 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2131&sSearch_string=angina

·

Guidelines for the management of patients with chronic stable angina. Source: American College of Cardiology/American College of Physicians-American Society of Internal Medicine/American Heart Association.; 1999 June; 105 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1192&sSearch_string=angina

·

Management of stable angina pectoris. Source: European Society of Cardiology.; 1997; 20 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1151&sSearch_string=angina

Guidelines 23

·

Management of stable angina. A national clinical guideline. Source: Scottish Intercollegiate Guidelines Network.; 2001 April; 26 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2142&sSearch_string=angina

·

Unstable angina pectoris. Source: Finnish Medical Society Duodecim.; 2001 April 30; Various pagings http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1842&sSearch_string=angina

Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

Facts About Angina Summary: This fact sheet distinguishes between angina and heart attacks and other causes of chest pain. Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=84

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to angina. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large

24 Angina

number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific conditions or disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

Family Village: http://www.familyvillage.wisc.edu/specific.htm

·

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

·

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

·

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Angina: Chest pain that originates in the heart. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Antibiotic: A drug that kills or inhibits the growth of bacteria. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH]

Guidelines 25

Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]

Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Catheter: Thin, flexible medical tube; one use is to insert it into a blood vessel to measure blood pressure. [NIH] CHD: Coronary heart disease. A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Cholesterol: A soft, waxy substance manufactured by the body and used in the production of hormones, bile acid, and vitamin D and present in all parts of the body, including the nervous system, muscle, skin, liver, intestines, and heart. Blood cholesterol circulates in the bloodstream. Dietary cholesterol is found in foods of animal origin. [NIH] Chronic: Of long duration; frequently recurring. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] ECG: Measurement of electrical activity during heartbeats. [NIH] Echocardiography: A test that bounces sound waves off the heart to produce pictures of its internal structures. [NIH] Electrocardiogram:

Measurement of electrical activity during heartbeats.

[NIH]

Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the

26 Angina

urine in diabetes mellitus. [EU] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH] HDL: Lipoproteins (high-density lipoproteins) that contain a small amount of cholesterol and carry cholesterol away from body cells and tissues to the liver for excretion from the body. Low-level HDL increases the risk of heart disease, so the higher the HDL level, the better. The HDL component normally contains 20 to 30 percent of total cholesterol, and HDL levels are inversely correlated with coronary heart disease risk. [NIH] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] LDL: Low-density lipoprotein. Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

Seeking Guidance 27

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with angina. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with angina. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Angina As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of a condition or disorder can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9

28 Angina

condition can all influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information, by consulting all of them, you will have nearly exhausted all sources for patient associations. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about angina. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “angina” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “angina”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making

Seeking Guidance 29

these selections and typing in “angina” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with angina. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific conditions and diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “angina” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with angina must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:11 ·

If you are in a managed care plan, check the plan’s list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

11

This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

30 Angina

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at 12 http://www.abms.org/newsearch.asp. You can also contact the ABMS by phone at 1-866-ASK-ABMS.

·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare conditions and diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 12

Seeking Guidance 31

Selecting Your Doctor13 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about angina?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

·

Address the health problem(s) I came with?

·

Ask me my preferences about different kinds of treatments for angina?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor14 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

13 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 14 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

32 Angina

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Seeking Guidance 33

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:15 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

15

Clinical Trials 35

CHAPTER 3. CLINICAL TRIALS AND ANGINA Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning angina.

What Is a Clinical Trial?16 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for angina is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

16

36 Angina

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on angina.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for angina compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on angina carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on angina. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on angina and does not harm patients.

Clinical Trials 37

Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how angina develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for angina. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a condition or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific condition or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of a condition or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help

38 Angina

find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Angina The National Institutes of Health and other organizations sponsor trials on various conditions and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to angina.17 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Outcome Study ONTARGET Condition(s): Coronary Disease; Angina Pectoris; Cerebrovascular Accident; Myocardial Infarction Study Status: This study is currently recruiting patients. Sponsor(s): Boehringer Ingelheim Pharmaceuticals Purpose - Excerpt: A large, simple, randomized, double-blind, multicentre, international trial comparing the effects of Telmisartan, Ramipril, and their combination on outcomes in patients at high risk for cardiovascular events. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00034931

·

Treatment of Non-Cardiac Chest Pain with Imipramine or CognitiveBehavioral Therapy Condition(s): Chest Pain

17

These are listed at www.ClinicalTrials.gov.

Clinical Trials 39

Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Approximately 75,000-150,000 patients each year in the United States undergo intensive cardiac evaluations for symptoms of angina-like chest pain that produce no positive findings. These patients often have high levels of disability and suffering and account for $250,000,000-$500,000,000 in estimated health care costs each year. There is some evidence from randomized, controlled trials that a pharmacologic agent, imipramine, and a program of training in pain coping skills and cognitive-behavioral therapy (CBT) both produce short-term reductions in pain intensity. However, no studies have compared the effects of these two treatments on measures of pain, suffering, and disability at posttreatment and over a one-year follow-up period. Our investigation is a 16-week, randomized controlled outcome study of these interventions and their respective placebo control procedures. One hundred and sixty patients are being recruited for this study. We will assess the effects of our interventions on patients' pain levels, quality of life, and health care resource usage at baseline, post-treatment, 6-month follow-up, and at 12month follow-up. We will evaluate the clinical significance of our treatment effects as well as their statistical significance. Phase(s): Phase III Study Type: Interventional Contact(s): Alabama; University of Alabama at Birmingham, Birmingham, Alabama, 35294, United States; Recruiting; Nancy McKendree-Smith, PhD 205-934-3911 [email protected]. Study chairs or principal investigators: Laurence A. Bradley, Principal Investigator; University of Alabama Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00005575 ·

Bypass Angioplasty Revascularization Investigation (BARI) Condition(s): Angina Pectoris; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Heart Diseases; Myocardial Ischemia Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To assess the relative long-term safety and efficacy of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) surgery in patients with multivessel disease and severe angina or ischemia who required revascularization and had coronary anatomy suitable for either procedure.

40 Angina

Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00000462 ·

Coronary Heart Disease Incidence, Mortality, and Risk Factor Relationships Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Infarction; Angina Pectoris Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the incidence, secular trends, and outcomes of coronary heart disease in the population of Rochester, Minnesota. Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00005148

·

Epidemiological Tool To Detect Angina Pectoris in Blacks Condition(s): Cardiovascular Diseases; Angina Pectoris; Heart Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To develop a prototype questionnaire for the detection of angina pectoris in Blacks. Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00005218

·

Multicenter Study of Silent Myocardial Ischemia (MSSMI) Condition(s): Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Myocardial Infarction; Angina, Unstable; Arrhythmia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if silent myocardial ischemia was associated with an increased risk of cardiac mortality and morbidity

Clinical Trials 41

during a one to three year follow-up in patients with coronary heart disease. Study Type: Epidemiology Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00005216 ·

Postmenopausal Hormone Therapy in Unstable Angina Condition(s): Angina, Unstable; Cardiovascular Diseases; Coronary Disease; Heart Diseases; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if estrogen therapy in postmenopausal women with unstable angina reduces the incidence of ischemic episodes. Phase(s): Phase III Study Type: Treatment, Prevention Contact(s):. Study chairs or principal investigators: Schulman, Steven P., Principal Investigator; Johns Hopkins University Baltimore, Maryland, United States Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00000601

·

Thrombolysis in Myocardial Ischemia Trial (TIMI III) Condition(s): Angina Pectoris; Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Infarction; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The Thrombolysis in Myocardial Ischemia Trial (TIMI III) focused on unstable angina and non-Q-wave myocardial infarction. The trial was designed to determine by coronary arteriography the incidence of coronary thrombi in these conditions and the response of these thrombi to tissue-type plasminogen activator (t-PA) in TIMI IIIA and the effects of thrombolytic therapy and of an early invasive strategy on clinical outcome in TIMI IIIB. There was also a registry with two components. A roster enumerated all patients with unstable angina or non-Q-wave myocardial infarction enrolled at cooperating hospitals. From the roster, a study population of 1,893 subjects was selected and followed prospectively for the year to determine incidence of death or myocardial infarction. Phase(s): Phase III

42 Angina

Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00000472 ·

Unstable Angina Pectoris Trial Condition(s): Angina, Unstable; Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare the efficacy of medical or surgical (coronary artery bypass graft) therapy with regard to survival and quality of life in patients with unstable angina and requisite coronary anatomy as defined by angiography. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00000486

Benefits and Risks18 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for angina. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve health or prevent diseases or disorders.

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291. 18

Clinical Trials 43

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with angina. In cases where certain conditions or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient. What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention. How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.

44 Angina

What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of you.

·

Know any costs involved for you or your insurance provider.

·

Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed).

What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don’t have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care.

Clinical Trials 45

What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for angina? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

·

What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will I have to come back for follow-up exams?

·

What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

·

How will my health be monitored?

·

Where will I need to go for the clinical trial? How will I get there?

·

How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

·

Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?

·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions.

46 Angina

The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “angina” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

·

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

·

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): · Clinical Trials in Cardiovascular Disease: A Companion to Braunwald’s Heart Disease by Charles H. Hennekens (Editor), et al; Hardcover (March 1999), W B Saunders Co; ISBN: 0721668674; http://www.amazon.com/exec/obidos/ASIN/0721668674/icongroupinterna ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

Clinical Trials 47

·

Handbook of Cardiovascular Clinical Trials by Shilpesh S. Patel, et al; Paperback - 427 pages, 1st edition (January 15, 1997), Churchill Livingstone; ISBN: 0443079250; http://www.amazon.com/exec/obidos/ASIN/0443079250/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Arteriography: Roentgenography of arteries after injection of radiopacque material into the blood stream. [EU] Cardiac: Pertaining to the heart. [EU] Cardiomyopathy: A disease of the heart muscle (myocardium). [NIH] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU]

48 Angina

Dyspnea: Shortness of breath; difficult or labored breathing. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Embolism: A sudden blocking of an artery by an embolus (clot or a foreign material such as a fat globule) brought to the site by the blood flow. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Hypertension: High blood pressure (i.e., abnormally high blood pressure tension involving systolic and/or diastolic levels). The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or taking hypertensive medication. The cause may be adrenal, benign, essential, Goldblatt's, idiopathic, malignant PATE, portal, postpartum, primary, pulmonary, renal or renovascular. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Menopause: The cessation of menstruation in the human female, which begins at about the age of 50. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy

Clinical Trials 49

accomplished by a needle. [EU] Perfusion: The passage of fluid through an organ. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Physiologic: Normal; not pathologic; characteristic of or conforming to the normal functioning or state of the body or a tissue or organ; physiological. [EU]

Plasminogen: The inactive precursor of plasmin (=enzyme that catalyses the hydrolysis of peptide bonds at the carbonyl end of lysine or arginine residues). [EU] Postmenopausal: Occurring after the menopause. [EU] Postmenopause: The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life. Since in the United States the age of the menopause ranges between 48 and 55 years, generally conceived as middle age, the postmenopause often refers to women considerably older. [NIH]

Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH]

Stenosis: Narrowing or stricture of a duct or canal. [EU] Sympathetic: 1. pertaining to, caused by, or exhibiting sympathy. 2. a sympathetic nerve or the sympathetic nervous system. [EU] Tachyarrhythmia: Tachycardia associated with an irregularity in the normal heart rhythm. [EU] Thrombolytic: 1. dissolving or splitting up a thrombus. 2. a thrombolytic agent. [EU] Ventricular: Pertaining to a ventricle. [EU] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH]

51

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on angina. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on angina. In Part II, as in Part I, our objective is not to interpret the latest advances on angina or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with angina is suggested.

Studies 53

CHAPTER 4. STUDIES ON ANGINA Overview Every year, academic studies are published on angina or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on angina. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on angina and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and angina, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the

54 Angina

format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “angina” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Prevalence of Nonfatal Coronary Heart Disease Among American Adults Source: American Heart Journal. 139(3):371-377, March 2000. Summary: Researchers analyzed data from the third National Health and Nutrition Examination Survey (NHANES III) to calculate the prevalence of coronary heart disease (CHD) in the United States by age, sex, and race or ethnic differences. The NHANES III was a survey of a nationally representative sample of United States adults conducted between 1988 and 1994 to estimate the prevalence of common chronic conditions and associated risk factors. Of 11,448 men and women age 40 years and older who participated in NHANES III, 9,737 attended the medical examination part of the survey. Results showed that (1) the age-adjusted prevalence of angina was 5.8 percent, of self-reported myocardial infarction was 6.7 percent, and of electrocardiogram (ECG)-defined myocardial infarction was 3.0 percent; (2) participants age 65 years and older had a 57 percent higher prevalence of angina, a 3-fold higher prevalence of self-reported myocardial infarction, and a more than 4-fold higher prevalence of ECG-defined myocardial infarction compared to participants age 40 to 64 years; and (3) men had about twice the rate of self-reported myocardial infarction and ECG-defined myocardial infarction as women. Other results showed that (1) ECG-defined myocardial infarction did not differ significantly between men and women among Hispanic Americans; (2) the prevalence of angina was higher among women than men among whites, blacks, and Hispanic Americans; (3) the sex difference for angina was significant only among blacks and Hispanic Americans; and (4) an estimated 11.8 percent of the United States population age 40 years and older had CHD. The researchers conclude that (1) there were significant race differences among women but not men, and (2) CHD remains an important prevalent disease burden among United States adults. 3 figures, 2 tables, 37 references.

Studies 55

·

Serum C-reactive Protein and Fibrinogen Concentrations and Selfreported Angina Pectoris and Myocardial Infarction: Findings From National Health and Nutrition Examination Survey III Source: Journal of Clinical Epidemiology. 53(1):95-102, January 2000. Summary: Researchers analyzed data from the third National Health and Nutrition Examination Survey (NHANES III) to assess whether Creactive protein and fibrinogen concentrations are independent predictors of self-reported angina pectoris and myocardial infarction. The NHANES III was a survey of a nationally representative sample of United States adults conducted between 1988 and 1994 to estimate the prevalence of common chronic conditions and associated risk factors. Of 5,226 men and 5,820 women age 40 years and older who were interviewed, 4,508 men and 4,858 women attended the medical examination part of the survey. Results showed that (1) 601 participants (5.8 percent), 256 men and 345 women, had self-reported angina; (2) the prevalence was 5.2 percent among men and 6.2 percent among women; (3) of 7,948 participants with data for C-reactive protein and fibrinogen, 545 participants had angina; and (4) 878 participants, 541 men and 337 women, had either self-reported myocardial infarction or electrocardiogram (ECG)-defined myocardial infarction. Participants with self-reported angina (1) were older and less educated; (2) had a higher serum cotinine concentration; (3) were more likely to have hypertension and a lower high density lipoprotein (HDL) cholesterol concentration; and (4) were more likely to be heavier, less active, and have diabetes. Participants with self-reported myocardial infarction (1) were older; (2) were more likely to be men and less educated; (3) were more likely to have hypertension, a higher cholesterol level, and a lower HDL cholesterol level; and (4) were more likely to be less active and have diabetes. Other results showed that (1) C-reactive protein and fibrinogen were strongly correlated; (2) body mass index and C-reactive protein were strongly correlated; (3) fibrinogen concentration was significantly associated with self-reported angina; (4) C-reactive protein was positively associated with myocardial infarction; (5) much of the effect of C-reactive protein appeared to be mediated through fibrinogen; and (6) significant predictors of angina included age, systolic blood pressure, and diabetes mellitus. The researchers conclude that these data showed a significant positive association between C-reactive protein concentration and myocardial infarction but not self-reported angina in the United States population. 5 tables, 41 references.

56 Angina

·

Drugs Used to Manage Cardiovascular Disease: Part IV-Nitrates and Other Antianginals Source: Access. 15(5): 64, 66, 68-69. May-June 2001. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: This article is one in a series that familiarizes dental hygienists with the drugs that may be use to manage cardiovascular disease; this fourth entry in the ongoing series focuses on nitrates and other antianginals. The series addresses the classes of medications used to manage a variety of cardiac conditions, including hypertension (HTN), angina, myocardial infarction, arrhythmias, heart murmurs, and stroke. Drug interactions, oral side effects, and general side effects of these cardiac medications are discussed, along with recommendations for client management and risk assessment strategies. In this article, the author focuses on nitrates, which are used for both the prevention and treatment of angina pectoris (chest pain), a common symptoms of ischemic (lack of blood flow) heart disease. Nitrates relieve the symptoms of angina by relaxing vascular smooth muscle, which vasodilates the large veins and causes pooling of blood on the venous side of the systemic circulation. This effect reduces the amount of blood that is returned to the heart, which in turn reduces the work of the heart. In addition, nitrates produce vasodilation of the coronary arteries, which improves blood flow to the myocardium. Other drugs discussed in this article are beta blockers, calcium channel blockers, and antithrombin and antiplatelet drugs. 5 tables. 9 references.

Federally-Funded Research on Angina The U.S. Government supports a variety of research studies relating to angina and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can 19 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies 57

perform targeted searches by various criteria including geography, date, as well as topics related to angina and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore angina and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for angina: ·

Project Title: Effect of Treatment with Azithromycin with Unstable Angina/Acute MI Principal Investigator & Institution: Cercek, Bojan; ; Harbor-Ucla Research & Educ Inst at Harbor-Ucla Medical Center Torrance, Ca 90502 Timing: Fiscal Year 2000 Summary: Patients who are admitted with rest angina are treated with a short 5-day treatment with Azithromycin. Azithromycin is an antibiotic, FDA approved and widely used for the treatment of the respiratory infections with Chlamydia pneunomiae. All other medications and treatment for the patients will be deemed necessary by the admitting physician. These patients are followed for six months and determined whether the treatment with Azithromycin prevents new coronary events. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

·

Project Title: Estrogen, Angina, Activity and Quality of Life in Women Principal Investigator & Institution: Missik, Eugeria; None; Kent State University at Kent Kent, Oh 44242 Timing: Fiscal Year 2001; Project Start 1-SEP-2001; Project End 1-AUG2004 Summary: Postmenopausal women comprise the largest number of female cardiac patients. Recently recognized vasoactive effects of estrogen have shown to improve coronary blood flow in postmenopausal cardiac women especially during exercise. Our recent pilot study conducted on 37 postmenopausal cardiac women identified some notable trends between women receiving hormone replacement therapy (HRT) and those women not receiving HRT. Women on HRT performed activities of higher intensity for longer periods of time, reported lower severity of angina, and higher quality of life. Studies on the relationship of hormonal status and daily physical activity of cardiac patients are not available. To what extent estrogen replacement therapy (ERT) impacts

58 Angina

the daily physical activity of postmenopausal cardiac patients is not known. It is hypothesized that the antischemic effects of estrogen positively impact daily physical activity and quality of life of postmenopausal cardiac women. Therefore, the primary aim of this study is to test a model examining the relationship between ERT use and frequency and severity of angina, daily physical activity, and quality of life. A prospective, comparative and cohort study will be used. Data will be collected on 180 postmenopausal cardiac women at three hospital based cardiac rehabilitation centers in western Pennsylvania. Multiple measures will be used for each construct in the model. Physical activity will be measured by self-report and electronic monitoring using the Tri Trac R3D accelerometer. Angina will be measured by the supplemented Rose Questionnaire, frequency by self-report, and severity by a numerical scale. Quality of life will be measured by using the Medical Outcomes Study, Short Form 36-Items. Structural equation analysis will be used to model the impact of ERT on the dependent variables. A demonstrated positive impact on physical activity may provide an additional rationale for the prudent use of ERT in the optimum management of postmenopausal cardiac patients. Interventions to support the adoption and maintenance of physical activity recommendations by postmenopausal cardiac women are greatly needed. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Gender Differences in the Symptoms of Unstable Angina Principal Investigator & Institution: Devon, Holli A.; Medical-Surgical Nursing; University of Illinois at Chicago at Chicago Chicago, Il 60612 Timing: Fiscal Year 2000; Project Start 9-SEP-2000 Summary: The objective of this proposal is to determine if there are gender differences in the symptoms of unstable angina, which are not explained by age, diabetes, or mood. A descriptive, quantitative study design will be used to identify the symptoms experienced prior to admission to the hospital for an acute episode of unstable angina. Fortyfive females and forty-five males will be interviewed. An open-ended question will be used to assess the patients' symptom experience in their own words. Instruments measuring type, location, and severity of symptoms, mood, and baseline characteristics will be used to identify and explicate the symptom experience. The description of symptoms is the mechanism by which patients gain entry to the health care system. In the acute setting, the descriptors used may affect triage in the emergency department, the use of cardiac interventions, and the course of treatment. The symptoms of a heart attack and/or unstable angina listed by the American Heart Association (AHA) and accepted by practitioners have

Studies 59

previously been based on a male model and may not be applicable to women. Recent studies, which have included women, suggest that there may be gender differences in the symptoms experienced with both acute myocardial infarction (AMI) and unstable angina. The majority of these studies have included only patients diagnosed with AMI. Because CHD in women is primarily manifested by angina and not AMI, many women have been excluded from analysis. This study will examine patients diagnosed with unstable angina in order to gather data that has been heretofore lacking in women. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Hirudin in Angina or Non-O Wave Infarction Principal Investigator & Institution: Chesebro, James H.; ; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2000; Project Start 1-OCT-1975; Project End 0-NOV2000 Summary: The objective of this study is to determine the optimal dosage of PEG-Hirudin in patients with unstable angina or non Q-wave myocardial infarction and also to compare its efficacy to that of standard drug therapy with heparin. The decision to give heparin, or to give PEGHirudin, will be made randomly by a computer after patient has given consent to participate. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

·

Project Title: Human FGF 4 Gene Transfer in Patients with Angina Principal Investigator & Institution: Brinker, Jeffrey A.; ; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2000 Summary: This is a Phase I/II clinical trial. The objective of this study is to evaluate the safety and anti-ischemic effects of adenovirus mediated hFGF-4 gene transfer in patients with stable exertional angina (Class II and Class III) so that a potentially safe and effective dose may be selected for a subsequent study. This is a double-blind, ascending dose, placebo controlled study. Each dose group consists of at least nine active and three placebo patients. The lowest dose (3.2 x 10"9 viral particles) will be studied first. For each dose group, safety observations during the first two weeks are reviewed and safety confirmed for the first patient randomized to active medication before dosing the second patient randomized to active medication. Safety observations for two weeks after the second patient are reviewed and safety confirmed before dosing the remaining patients in each dose group. Sponsor unblinding for all

60 Angina

patients is allowed, but the patient, investigator, and his staff all remain blinded throughout the study. Core laboratories read, in a blinded fashion, exercise ECGs, stress echocardiograms, and coronary angiography. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Improving the Evidence for Unstable Angina Guidelines Principal Investigator & Institution: Katz, David M.; Associate Professor; Medicine; University of Wisconsin Madison 500 Lincoln Dr Madison, Wi 53706 Timing: Fiscal Year 2000; Project Start 1-SEP-2000; Project End 1-AUG2002 Summary: This project aims to improve the evidence base for the AHCPR Unstable Angina Practice Guideline, which challenges clinicians to consider outpatient management for low-risk patients with symptoms suggestive of acute cardiac ischemia (ACI). Capitalizing on the resources of two clinical effectiveness trials of ED decision making, the Acute Cardiac Ischemia Time Insensitive Predictive Instrument (ACI-TIPI) Impact Trial and the nearly completed Sestamibi Scan Clinical Trial, this project will determine whether agreement with guideline recommendations for triage is associated with decreased short-term rates of adverse outcomes (non-fatal myocardial infarction and death) and decreased short-term utilization (ED revisits, readmissions, coronary angiography, and revascularization). Through chart review, we will abstract items necessary to categorize 9191 study patients according to their risk of adverse short term outcomes, based on AHCPR triage guidelines and other unstable angina risk stratification models. For each guideline risk group, we will test the independent contribution of triage disposition to the prediction of adverse outcomes in hierarchical logistic regression models, controlling for the patient-level, physician-level, and hospital-level predictors of adverse outcomes. As unbalanced distribution of these predictors may bias comparisons of adverse outcome in "guideline- concordant" versus "guideline-discordant" triage disposition groups, we will examine two approaches for case-mix adjustment: propensity scores and ACI-TIPI scores. As several other existing instruments, in addition to guidelines, may improve decisionmaking in acute cardiac care, we will also compute the sensitivity and specificity of the guideline's risk groups in discriminating between patients with and without adverse short-term outcomes, compared to that of other available prognostic models for ACI. The proposed research will provide policymakers with the ability to project the impact of

Studies 61

guideline implementation on outcomes, cost, and the use of health care services for patients with symptoms suggestive of unstable angina. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Pilot--Perception of Anginal Chest Pain in CAD Principal Investigator & Institution: Kimble, Laura P.; ; Emory University 1380 S Oxford Rd Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 1-JUL-2001; Project End 0-JUN2004 Summary: The purpose of this pilot study is to explore relationships between anginal pain, sleep disturbance, and quality of life in coronary artery disease (CAD) patients, focusing on differences in symptom perceptions according to gender and status on the CAD illness trajectory. The Symptom Interactional Framework of sleep alterations and pain will serve as the theoretical base for the study. The study will have a prospective design and will be conducted in the outpatient cardiac catheterization laboratory of Emory Clinic, Emory University. Inclusion criteria include adults of any age, gender, and ethnicity who (a) are able to speak English, (b) have received a new diagnosis of CAD following elective coronary angiography or have received elective coronary angiography to evaluate status of known CAD, and (c) have a history of angina. In order to adequately address the research questions posed, the sample will be stratified by gender and by status on the CAD illness trajectory so that an equal number of males/females and newly diagnosed CAD patients on the CAD illness trajectory so that an equal number of males/females and newly diagnosed CAD patients in patients with a previous history of CAD will be represented in the analyses. A sample size of 84 subjects is proposed. Because effect size estimation is difficult (because difference between newly diagnosed CAD patients and those with a history of CAD have rarely been compared on the proposed study variables), the standard convention of a medium effect size with two- tailed alpha of .05 and a power of .80 was used to calculate sample size. Established data collection instruments will include the Chest Discomfort Diary, the Rose Questionnaire, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, and the Maastricht Questionnaire. Subjects will answer questions regarding chest pain, sleep disturbances, and vital exhaustion within eight hours following coronary angiography. Initial data analysis will include descriptive statistics on sample characteristics, examination for type and extent of any missing data, and assessment of psychometric properties for all study instruments. Independent samples t- tests and Pearson product moment correlations will be used to answer the three research questions. It is likely that more

62 Angina

extensive modeling including logistic regression and/or discriminant analysis will be done for the third research question. While the study of sleep disturbances and angina is now a new area of inquiry, the proposed project has the potential to contribute to the literature by including strong conceptualization and measurement of anginal pain and sleep disturbances. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central20 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).21 Access to this growing archive of e-journals is free and unrestricted.22 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “angina” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for angina in the PubMed Central database: ·

A comparison of the illness beliefs of people with angina and their peers: a questionnaire study by Gill Furze, Alun Roebuck, Peter Bull, Robert J. P. Lewin, and David R. Thompson; 2002 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88998

·

Barriers to referral in patients with angina: qualitative study by Katy Gardner and Alison Chapple; 1999 August 14 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28197

·

Debate: Unstable angina - When should we intervene? by Dean J Kereiakes; 2000 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59588

·

Debate: When should we intervene in unstable angina - Time for an old look? by Warren K Laskey; 2000 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59589

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 21 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 22 The value of PubMed Central, in addition to its role as an archive, lies the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 20

Studies 63

·

Drug points:Exacerbation of angina associated with latanoprost by M Mitra, B Chang, and T James; 2001 October 6 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=57357

·

Expression of lipocalin-type prostaglandin D synthase ([beta]-trace) in human heart and its accumulation in the coronary circulation of angina patients by Yutaka Eguchi, Naomi Eguchi, Hiroshi Oda, Kousuke Seiki, Yoshiyuki Kijima, Yasuhiko Matsu-ura, Yoshihiro Urade, and Osamu Hayaishi; 1997 December 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=25094

·

Impact of reference-based pricing of nitrates on the use and costs of anti-anginal drugs by Paul V. Grootendorst, Lisa R. Dolovich, Bernie J. O'Brien, Anne M. Holbrook, and Adrian R. Levy; 2001 October 16 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=81535

·

Randomised controlled trial of follow up care in general practice of patients with myocardial infarction and angina: final results of the Southampton heart integrated care project (SHIP) by Kate Jolly, Fiona Bradley, Stephen Sharp, Helen Smith, Simon Thompson, Ann-Louise Kinmonth, and David Mant; 1999 March 13 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27782

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to the public.23 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with angina, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “angina” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “angina” (hyperlinks lead to article summaries): PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

23

64 Angina

·

High-dose monotherapy and combination therapy with calcium channel blockers for angina. A comprehensive review of the literature. Author(s): Temkin LP. Source: The American Journal of Medicine. 1989 January 16; 86(1A): 23-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2563636&dopt=Abstract

·

Images in cardiology. Multiple ecchymotic lesions on the torso of a patient with unstable angina. Author(s): Sadaniantz A, Gordon PC. Source: Clin Cardiol. 2000 March; 23(3): 214-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10761813&dopt=Abstract

·

Immediate effect of Kuan-xiong aerosol in the treatment of anginal attacks. Author(s): Guo SK, Chen KJ, Weng WL, Zhang WQ, Yu YQ. Source: Planta Medica. 1983 February; 47(2): 116. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6844452&dopt=Abstract

·

Indigenous free radical scavenger MAK 4 and 5 in angina pectoris. Is it only a placebo? Author(s): Dogra J, Grover N, Kumar P, Aneja N. Source: J Assoc Physicians India. 1994 June; 42(6): 466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7852231&dopt=Abstract

·

Influence of naloxone on the effects of high frequency transcutaneous electrical nerve stimulation in angina pectoris induced by atrial pacing. Author(s): Mannheimer C, Emanuelsson H, Waagstein F, Wilhelmsson C. Source: Br Heart J. 1989 July; 62(1): 36-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2788001&dopt=Abstract

·

Lasers, burns, cuts, tingles and pumps: a consideration of alternative treatments for intractable angina. Author(s): Mulcahy D, Knight C, Stables R, Fox K.

Studies 65

Source: Br Heart J. 1994 May; 71(5): 406-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8011401&dopt=Abstract ·

Long-term study of high-dose diltiazem in chronic stable exertional angina. Author(s): Hossack KF, Kannagi T, Day B, Bruce RA. Source: American Heart Journal. 1984 June; 107(6): 1215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6720548&dopt=Abstract

·

Management of post-thoracotomy pseudoangina and myofascial pain with botulinum toxin. Author(s): Diaz JH, Gould HJ 3rd. Source: Anesthesiology. 1999 September; 91(3): 877-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10485804&dopt=Abstract

·

Musculoskeletal chest pain in patients with "angina": a prospective study. Author(s): Levine PR, Mascette AM. Source: Southern Medical Journal. 1989 May; 82(5): 580-5, 591. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2717982&dopt=Abstract

·

Neuromodulation for chronic refractory angina. Author(s): Moore R, Chester M. Source: British Medical Bulletin. 2001; 59: 269-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11756216&dopt=Abstract

·

Neurostimulation treatment for angina pectoris. Author(s): Murray S, Collins PD, James MA. Source: Heart (British Cardiac Society). 2000 February; 83(2): 217-20. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10648501&dopt=Abstract

·

Occupation, type A behavior and self-reported angina pectoris. Author(s): Byrne DG, Reinhart MI.

66 Angina

Source: Journal of Psychosomatic Research. 1989; 33(5): 609-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2795533&dopt=Abstract ·

Prompt relief of vasospastic angina by calcium antagonists. Author(s): Egashira K, Araki H, Tomoike H, Takeshita A, Nakamura M. Source: Int J Clin Pharmacol Ther Toxicol. 1987 April; 25(4): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3108169&dopt=Abstract

·

Psychotherapeutic intervention in angina: I. A critical review. Author(s): Razin AM. Source: General Hospital Psychiatry. 1984 October; 6(4): 250-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6489743&dopt=Abstract

·

Quantitative evaluation of vitamin E in the treatment of angina pectoris. Author(s): Gillilan RE, Mondell B, Warbasse JR. Source: American Heart Journal. 1977 April; 93(4): 444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=320856&dopt=Abstract

·

Refractory angina pectoris in end-stage coronary artery disease: evolving therapeutic concepts. Author(s): Schoebel FC, Frazier OH, Jessurun GA, De Jongste MJ, Kadipasaoglu KA, Jax TW, Heintzen MP, Cooley DA, Strauer BE, Leschke M. Source: American Heart Journal. 1997 October; 134(4): 587-602. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9351724&dopt=Abstract

·

Refractory angina pectoris: mechanism and therapeutic options. Author(s): Kim MC, Kini A, Sharma SK. Source: Journal of the American College of Cardiology. 2002 March 20; 39(6): 923-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11897431&dopt=Abstract

·

Respiratory compromise: a rare complication of transcutaneous electrical nerve stimulation for angina pectoris. Author(s): Mann CJ.

Studies 67

Source: Journal of Accident & Emergency Medicine. 1996 January; 13(1): 68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8821235&dopt=Abstract ·

Response of anginal pain to hand warming. A clinical note. Author(s): Hartman CH. Source: Biofeedback Self Regul. 1979 December; 4(4): 355-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=393305&dopt=Abstract

·

Safety and efficacy of Hartone in stable angina pectoris--an open comparative trial. Author(s): Kumar PU, Adhikari P, Pereira P, Bhat P. Source: J Assoc Physicians India. 1999 July; 47(7): 685-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10778587&dopt=Abstract

·

Spinal cord stimulation in severe angina pectoris--presentation of current studies, indications and clinical experience. Author(s): Eliasson T, Augustinsson LE, Mannheimer C. Source: Pain. 1996 May-June; 65(2-3): 169-79. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8826504&dopt=Abstract

·

TENS in chronic angina. Author(s): Marshall P. Source: Prof Nurse. 1991 October; 7(1): 20-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1946478&dopt=Abstract

·

TENS in refractory angina pectoris. Three case reports. Author(s): West PD, Colquhoun DM. Source: Med J Aust. 1993 April 5; 158(7): 488-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8469202&dopt=Abstract

·

The challenge of angina. Author(s): Ryde D.

68 Angina

Source: Br J Gen Pract. 1996 December; 46(413): 759. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8995872&dopt=Abstract ·

The effect of transcutaneous electrical nerve stimulation (TENS) on catecholamine metabolism during pacing-induced angina pectoris and the influence of naloxone. Author(s): Mannheimer C, Emanuelsson H, Waagstein F. Source: Pain. 1990 April; 41(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2352762&dopt=Abstract

·

The effects of transcutaneous electrical nerve stimulation in patients with severe angina pectoris. Author(s): Mannheimer C, Carlsson CA, Emanuelsson H, Vedin A, Waagstein F, Wilhelmsson C. Source: Circulation. 1985 February; 71(2): 308-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3871177&dopt=Abstract

·

The relationship of stress management training to the experience of pain in clients with intractable angina. Author(s): Woods JH, Minniti MJ. Source: Journal of Holistic Nursing : Official Journal of the American Holistic Nurses' Association. 1987 Spring; 5(1): 11-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3668219&dopt=Abstract

·

The successful use of spinal cord stimulation to alleviate intractable angina pectoris. Author(s): McCleane GJ. Source: Ulster Med J. 1998 May; 67(1): 59-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9652202&dopt=Abstract

·

Therapeutic effect of Crataegus pinnatifida on 46 cases of angina pectoris--a double blind study. Author(s): Weng WL, Zhang WQ, Liu FZ, Yu XC, Zhang PW, Liu YN, Chi HC, Yin GX, Huang MB.

Studies 69

Source: J Tradit Chin Med. 1984 December; 4(4): 293-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6397664&dopt=Abstract ·

Total occlusion of left main coronary artery without angina pectoris. Author(s): DePace NL, Kimbiris D, Iskandrian AS, Bemis CE, Segal BL. Source: Archives of Internal Medicine. 1983 May; 143(5): 1064-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6679220&dopt=Abstract

·

Transcutaneous electrical nerve stimulation (TENS) for treatment of severe angina pectoris refractory to maximal medical and surgical management--a case report. Author(s): Magarian GJ, Leikam B, Palac R. Source: Angiology. 1990 May; 41(5): 408-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1972613&dopt=Abstract

·

Transcutaneous electrical nerve stimulation (TENS) in angina pectoris. Author(s): Mannheimer C, Carlsson CA, Vedin A, Wilhelmsson C. Source: Pain. 1986 September; 26(3): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3534690&dopt=Abstract

·

Transcutaneous electrical nerve stimulation in severe angina pectoris. Author(s): Mannheimer C, Carlsson CA, Ericson K, Vedin A, Wilhelmsson C. Source: European Heart Journal. 1982 August; 3(4): 297-302. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6982163&dopt=Abstract

·

Transcutaneous electrical nerve stimulation in unstable angina pectoris. Author(s): Borjesson M, Eriksson P, Dellborg M, Eliasson T, Mannheimer C. Source: Coronary Artery Disease. 1997 August-September; 8(8-9): 543-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9431483&dopt=Abstract

70 Angina

·

Treatment of angina pectoris with medicinal plaster fixed at acupoints-a report of 54 cases. Author(s): Liu Y, Wang T, Zhang J. Source: J Tradit Chin Med. 1998 March; 18(1): 12-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10437254&dopt=Abstract

·

Treatment of unstable angina pectoris based on disease- and syndrome-differentiation. Author(s): Zhong J, Shi D. Source: J Tradit Chin Med. 2000 June; 20(2): 141-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11039008&dopt=Abstract

·

Unstable angina pectoris--changes in the ST-T segment during daily activities such as bathing, eating, defecating and urinating. Author(s): Tanabe T, Goto Y. Source: Jpn Circ J. 1983 April; 47(4): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6834649&dopt=Abstract

·

Unstable angina with tachycardia: clinical and therapeutic implications. Author(s): Sclarovsky S, Bassevich R, Strasberg, Klainman E, Rechavia E, Sagie A, Agmon J. Source: American Heart Journal. 1988 November; 116(5 Pt 1): 1188-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3189136&dopt=Abstract

·

Vasospastic angina likely related to cisplatin-containing chemotherapy and thoracic irradiation for lung cancer. Author(s): Fukuda M, Oka M, Itoh N, Sakamoto T, Mori H, Hayakawa A, Kohno S. Source: Intern Med. 1999 May; 38(5): 436-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10397083&dopt=Abstract

·

Vindesine-associated angina and ECG changes. Author(s): Yancey RS, Talpaz M.

Studies 71

Source: Cancer Treat Rep. 1982 March; 66(3): 587-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7060049&dopt=Abstract ·

Visceral chest pain in unstable angina pectoris and effects of transcutaneous electrical nerve stimulation. (TENS). A review. Author(s): Borjesson M. Source: Herz. 1999 April; 24(2): 114-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10372297&dopt=Abstract

Vocabulary Builder Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Anesthesiology: A specialty concerned with the study of anesthetics and anesthesia. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antibiotics: Substances produced by microorganisms that can inhibit or suppress the growth of other microorganisms. [NIH] Antibodies: Specific proteins produced by the body's immune system that bind with foreign proteins (antigens). [NIH] Arginine: An essential amino acid that is physiologically active in the Lform. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU]

72 Angina

Asymptomatic: Showing or causing no symptoms. [EU] Auditory: Pertaining to the sense of hearing. [EU] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bilateral: Having two sides, or pertaining to both sides. [EU] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Catheterization: The employment or passage of a catheter. [EU] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Chlamydia: A genus of the family chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is chlamydia trachomatis. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clostridium: A genus of motile or nonmotile gram-positive bacteria of the family bacillaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals. [NIH] Colitis: Inflammation of the colon. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU]

Studies 73

Diastolic: Of or pertaining to the diastole. [EU] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Electrocardiography: The making of graphic records of the variations in electrical potential caused by electrical activity of the heart muscle and detected at the body surface, as a method for studying the action of the heart muscle. [EU] Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels, and the serous cavities of the body, originating from the mesoderm. [EU] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Fibrinogen: A plasma protein that is converted into fibrin by thrombin in the presence of calcium ions. Fibrin is responsible for the semisolid character of a blood clot. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU]

74 Angina

Hirudin: The active principle in the buccal gland secretion of leeches. It acts as an antithrombin and as an antithrombotic agent. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH]

Hyperventilation: A state in which there is an increased amount of air entering the pulmonary alveoli (increased alveolar ventilation), resulting in reduction of carbon dioxide tension and eventually leading to alkalosis. [EU] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intubation: Insertion of a tube into an organ in the body. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lipoprotein: Protein-coated packages that carry fat and cholesterol throughout the bloodstream. There are four general classes: high-density, low-density, very low-density, and chylomicrons. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mediastinitis: Inflammation of the mediastinum, the area between the pleural sacs. [NIH] Microcirculation: The flow of blood in the entire system of finer vessels (100 microns or less in diameter) of the body (the microvasculature). [EU] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a

Studies 75

dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] MMPI: A personality inventory consisting of statements to be asserted or denied by the individual. The patterns of response are characteristic of certain personality attributes. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monotherapy: A therapy which uses only one drug. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] NHANES: National Health and Nutrition Examination Survey; conducted every 10 years by the National Center for Health Statistics to survey the dietary habits and health of U.S. residents. [NIH] Nicorandil: A derivative of the niacinamide that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU]

76 Angina

Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU]

Studies 77

Refractory: Not readily yielding to treatment. [EU] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Respiratory: Pertaining to respiration. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Stabilization: The creation of a stable state. [EU] Sublingual: Located beneath the tongue. [EU] Systemic: Relating to a process that affects the body generally; in this instance, the way in which blood is supplied through the aorta to all body organs except the lungs. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart; the term is usually applied to a heart rate above 100 per minute and may be qualified as atrial, junctional (nodal), or ventricular, and as paroxysmal. [EU] Thoracic: Pertaining to or affecting the chest. [EU] Thoracotomy: Surgical incision into the chest wall. [NIH]

78 Angina

Thrombosis: The formation, development, or presence of a thrombus. [EU] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trismus: Motor disturbance of the trigeminal nerve, especially spasm of the masticatory muscles , with difficulty in opening the mouth; a characteristic early symptom of tetanus. Called also lockjaw. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasomotor: 1. affecting the calibre of a vessel, especially of a blood vessel. 2. any element or agent that effects the calibre of a blood vessel. [EU] Veins: The vessels carrying blood toward the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU]

Patents 79

CHAPTER 5. PATENTS ON ANGINA Overview You can learn about innovations relating to angina by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.24 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available to patients with angina within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available to patients with angina. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

24Adapted

from the U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

80 Angina

Patents on Angina By performing a patent search focusing on angina, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on angina:

·

Therapeutic use of(R)-Verapamil for treating angina Inventor(s): Harding; Deborah Phyllis (Cambridge, GB) Assignee(s): Darwin Discovery Limited (GB) Patent Number: 5,889,060 Date filed: August 6, 1997 Abstract: (R)-verapamil, or a pharmaceutically-acceptable salt thereof, is useful in the treatment of angina. Excerpt(s): This invention relates to the use of verapamil in the treatment of angina. ... Angina is a common indication of myocardial ischaemia either as a result of coronary artery disease or post acute myocardial infraction. ... Satoh et al, Journal of Cardiovascular Pharmacology (1980) 2:309-318 disclose details of a study of the vasodilatory and cardiodepressant effects of the two enantiomers of verapamil. The authors report that a equieffective doses in terms of increasing coronary sinus outflow, (R)-verapamil is significantly less cardiodepressant than (S)-verapamil. They conclude from this that (R)-verapamil may provide a safer means of treating angina than (S)-verapamil, but add that it is not known which of the enantiomers of verapamil is of grater therapeutic value in the treatment of angina. Web site: http://www.delphion.com/details?pn=US05889060__

·

Method and apparatus for providing feedback to spinal cord stimulation for angina Inventor(s): Rise; Mark T. (Monticello, MN) Assignee(s): Medtronic Inc. (Minneapolis, MN) Patent Number: 5,824,021 Date filed: July 22, 1997

Patents 81

Abstract: Techniques for cardiac monitoring and angina pectoris treatment using a cardiac condition detector and stimulating electrode. The detector and electrode are implanted. Angina is relieved by transmitting electrical pulses to the stimulating electrode while the patient is giving an indication of an ischemic event that otherwise would be indicated by the angina. Excerpt(s): This invention relates to techniques for relieving angina, and more particular relates to such techniques for detecting the occurrence of an ischemic event while angina is being relieved. ... Spinal cord stimulation to treat intractable angina has been suggested. D. F. Murphy, et. al. describe the clinical results of such a technique in "Column Stimulation for Pain Relief from Intractable Angina Pectoris", Pain, Volume 28, 1987, at 363-368, incorporated herein by reference. Bourgeois (U.S. Pat. No. 5,058,584) describes a method and apparatus for applying the stimulation only when the subject is increasing physical activity and as such causes the occurrence of angina. Bourgeois assumes blood flow to the heart is increased by spinal cord stimulation. Therefore the application of stimulation during times of increased activity will increase coronary blood flow and reduce the likelihood that the patient will experience pain. However, there is still controversy about whether the stimulation of the spinal cord increases the blood flow to the heart thereby reducing angina or if it merely masks the pain. Of concern is the possibility that by masking angina pain using spinal cord stimulation, the patient may be put at greater risk for an infarct by causing the patient to ignore or not perceive the signs of cardiac ischemia and overexert himself This invention addresses that problem. ... The invention can be used for cardiac monitoring and angina pectoris treatment of a patient by using a cardiac condition detector and a stimulating electrode. According to a preferred embodiment, the detector is placed at a recording site either adjacent the patient or in the patient. A stimulating electrode is implanted adjacent the spinal cord or in the spinal cord of the patient. Indicia of the condition of the heart muscle of the patient are received at the detector and are processed to detect the occurrence of an ischemic event. An indication of the occurrence of the ischemic event detectable by the patient is produced. Electrical pulses suitable for stimulating the spinal cord to reduce angina are also generated. The pulses are gated to the stimulating electrode so that the angina pectoris is reduced while the patient is given an indication of an ischemic event that otherwise would be indicated by the angina pectoris. Web site: http://www.delphion.com/details?pn=US05824021__

82 Angina

·

Methods and compositions for treating hypertension, angina and other disorders using optically pure s(-) nitrendipine Inventor(s): Barberich; Timothy J. (Concord, MA), Young; James W. (Palo Alto, CA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 5,571,827 Date filed: June 15, 1994 Abstract: Methods and compositions are disclosed utilizing the optically pure S(-) isomer of nitrendipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the administration of the racemic mixture of nitrendipine. The S(-) isomer of nitrendipine is also useful for the treatment of angina and such other conditions as may be related to the activity of S(-) nitrendipine as a calcium channel antagonist without the concomitant liability of adverse effects associated with the racemic mixture of nitrendipine. Excerpt(s): This invention relates to novel compositions of matter containing optically pure S(-) nitrendipine. These compositions possess potent activity in treating both systolic and diastolic hypertension while avoiding adverse effects including but not limited to insulin resistance, edema of the extremities, headache, dizziness, flushing and weakness which are associated with administration of the racemic mixture of nitrendipine. Additionally, these novel compositions of matter containing optically pure S(-) nitrendipine are useful in treating angina and such other conditions as may be related to the activity of S(-) nitrendipine as a calcium channel antagonist including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure--while avoiding the adverse effects associated with administration of the racemic mixture of nitrendipine. Also disclosed are methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of nitrendipine, by administering the optically pure S(-) isomer of nitrendipine to said human. ... Furthermore, the racemic mixture of nitrendipine is useful in treating other disorders such as angina pectoris. Angina pectoris is a clinical syndrome reflecting myocardial ischemia. A condition where cardiac work or myocardial oxygen demand exceeds the ability of the coronary arterial vascular system to supply oxygen results in myocardial ischemia, which may cause either a painful angina attack or an angina attack that is not accompanied by pain (silent ischemia). Under extreme circumstances, the lack of oxygen may cause a myocardial

Patents 83

infarction or cardiac arrhythmias. The treatment of angina is directed to the underlying disease, usually atherosclerosis, or to drugs which either reduce myocardial oxygen demand or improve oxygen supply. Calcium antagonists such as nitrendipine have been particularly useful in treating vasospastic angina, the angina of effort, and the unstable angina, due to the effect of the calcium channel antagonist on cardiac and vascular smooth muscle. ... It has now been discovered that the optically pure S(-) isomer of nitrendipine is an effective antihypertensive agent for both systolic and diastolic hypertension, particularly in mild to moderate disease and angina, which avoids the adverse effects including but not limited to insulin resistance, edema of the extremities, headache, flushing, weakness and dizziness which are associated with the administration of the racemic mixture of nitrendipine. It has also been discovered that these novel compositions of matter containing optically pure S(-) nitrendipine are useful in treating other conditions as may be related to the activity of S(-) nitrendipine as a calcium channel antagonist, including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure while avoiding the above-described adverse effects associated with the administration of the racemic mixture of nitrendipine. The present invention also includes methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of nitrendipine by administering the S(-) isomer of nitrendipine to said human. Web site: http://www.delphion.com/details?pn=US05571827__ ·

Treatment of angina pectoris Inventor(s): Goldberg; Arthur H. (Montclair, NJ), Lachman; Leonard (Fort Salonga, NY) Assignee(s): RiboGene, Inc. (Hayward, CA) Patent Number: 5,498,636 Date filed: December 2, 1994 Abstract: This invention relates to a method for treating angina pectoris. Pursuant to this method, a .beta.-adrenergic-blocking agent is administered acutely to a person having angina to provide an essentially immediate, therapeutic amount of bioavailable blocking agent. The invention further relates to a method wherein the blocking agent is nasally administered for this purpose.

84 Angina

Excerpt(s): The present invention relates to a novel method for treatment of angina pectoris. A .beta.-adrenergic-blocking agent is administered acutely to a patient having angina. The dose is desirably provided by nasal administration to provide an essentially immediate, therapeutically effective amount of blocking agent to treat the angina. ... Angina occurs when cardiac work and myocardial oxygen demand exceed the ability of the coronary arteries to supply oxygenated blood. The myocardium becomes ischemic and, accompanied by myriad physiological and chemical changes, symptoms such as pain result. ... The discomfort of angina pectoris is most commonly felt beneath the sternum. It may range from a vague ache to an intense precordial crushing sensation. It may also radiate, usually to the left shoulder and arm, but also through the back, into the throat, jaws and/or teeth and elsewhere. Anginal discomfort may even be felt in the upper or lower abdomen. Web site: http://www.delphion.com/details?pn=US05498636__ ·

Pharmaceutical hydrophilic spray containing nitroglycerin for treating angina Inventor(s): Klokkers-Bethke; Karin (Monheim/Rhld., DE), Munch; Ulrich (Monheim/Rhld., DE) Assignee(s): Schwarz Pharma AG (Monheim, DE) Patent Number: 5,370,862 Date filed: December 11, 1992 Abstract: A pharmaceutical aerosol spray for treating an angina attack including a container having a liquid composition therein comprising 0.1 to 2 weight percent of nitroglycerin, 2 to 60 weight percent of ethanol, 2 to 60 weight percent of propylene glycol, 10 to 50 weight percent of dichlorodifluoromethane and 30 to 70 weight percent of dichlorotetrafluoroethane, the container having a valve assembly sealed to the container around an opening in the container by a sealant material which has a nitroglycerin absorption value less than 10 mg/1 g of sealant material. Excerpt(s): Nitroglycerin, also called glycerol trinitrate or GTN, is an active substance for the treatment of angina pectoris attacks. Among other things, it is used in emergencies when the medication should be fast acting. ... The pharmaceutical agents used for this specific purpose, such as sublingual tablets or crunchable capsules, have disadvantages. A disadvantage, amongst others, is that after intake the active agent in these pharmaceutical agents must first be released and dispersed prior to being available for resorption in dissolved form. Furthermore, the loss of time

Patents 85

needed to take the pharmaceutical agent out of a blister package can be critical during an acute angina attack. ... Because of the low solubility of nitroglycerin in water the solvents used in the customary spray formulations are lipophilic, i.e. oils or triglycerides. However, the lipophilic solvents prevent dispersion of the active agent nitroglycerin into the hydrophilic mucosa with the desired speed during acute angina pectoris attacks. Web site: http://www.delphion.com/details?pn=US05370862__ ·

Use of baclofen for the treatment of angina pectoris Inventor(s): Bousquet; Pascal-Pierre (Strasbourg, FR) Assignee(s): Adir et Compagnie () Patent Number: 5,149,713 Date filed: May 22, 1991 Abstract: The invention relates to the use of baclofen for the treatment of angina pectoris. Excerpt(s): The Applicants have now found that baclofen has valuable pharmacological properties that can be used in obtaining medicaments for the treatment of angina pectoris. ... Pharmacological tests have shown that baclofen is an antianginal substance because it prevents an increase in the oxygen requirement in situations triggering angina pectoris attacks, without depressing the basic functioning of the heart. In the case of humans, these situations are physical effort and stress (Braunwald "Heart Disease, A textbook of cardiovascular medicine", ED Saunders W.B (1980) pp. 1387-1389). ... The invention extends also to pharmaceutical compositions that can be used in the treatment of angina pectoris and contain as active ingredient the compound of the formula I or one of its salts with a pharmaceutically compatible mineral or organic acid, in association with one or more suitable inert excipients. The compound of the formula I or one of its addition salts may also be associated with other compounds used in the treatment of angina pectoris, such as, for example, calcium-blocking agents or betablockers. Web site: http://www.delphion.com/details?pn=US05149713__

86 Angina

·

Method and apparatus for epidural burst stimulation for angina pectoris Inventor(s): Bourgeois; Ivan (Verviers, BE) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 5,058,584 Date filed: August 30, 1990 Abstract: Method of and apparatus for the treatment of angina pectoris using electrical stimulation within the epidural space of the spinal cord. A sensor is used to trigger stimulation only during periods of activity assumed to be symptomatic. The sensor may measure any of a number of parameters including blood oxygen saturation level or mechanical activity. In the preferred embodiment, a piezoelectric activity sensor is programmed to determine when the level of activity is reached at which angina is expected to occur in a particular patient. This determination is used to trigger an implantable pulse generator. Bursts of high frequency stimulation energy are applied by an insulated lead to electrodes implanted in the epidural space at an upper thoracic or lower cervical location. The increased neural activity caused by the stimulation bursts eliminates the pain sensation and allows an equal or higher exercise level of the patient without pain or at a similar pain level. The epidural stimulation does not decrease coronary perfusion at the same exercise level. When sensed body activity decreases below a second programmed level, electrical stimulation is inhibited. Excerpt(s): The present invention relates generally to medical devices, and more particularly, relates to implantable medical devices for the treatment of angina pectoris. ... The high prevalence of angina pectoris in modern society is well documented. The current standard therapy usually relies upon nitroglycerine various vasodilators to increase perfusion and beta-blockers and other chemical agents to control coronary perfusion and pain. Normally surgical intervention or angioplasty is required to chronically increase profusion in those patients for whom such a procedure is indicated. ... A newly discovered technique for angina patients involves electrical stimulation of the spinal cord. D. F. Murphy, et al. describe the clinical results of such a technique in "Dorsal Column Stimulation for Pain Relief from Intractable Angina Pectoris", Pain, Volume 28, 1987, at 363-368, incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05058584__

Patents 87

·

Nitrate therapy for angina pectoris Inventor(s): Bayer; Gerald W. (Rochester, NY), Diamantopoulos; Paul A. (Rochester, NY), Osterhoudt; Hans W. (Spencerport, NY), Schmit; Paul F. (Rochester, NY) Assignee(s): Eastman Kodak (Rochester, NY) Patent Number: 4,956,181 Date filed: June 7, 1988 Abstract: Method and device for treating angina pectoris and preventing tolerance to nitrate drugs which takes into account the frequent need to provide the patient with relief from or prevention of pre-waking or early morning angina. The treatment comprises administering a daily unit dose of the nitrate before bedtime in a dosage form that (1) provides a washout period of 3 to 12 hours by sufficiently retarding delivery of the nitrate to the patient during the washout period so as to provide a rate of delivery of nitrate from the patch that is so low as to be insufficient to cause tolerance to said nitrate in said patient; (2) at the end of the washout period and at least 30 minutes before the patient expects to awaken, initiates an effective delivery period during which the dosage form provides an initial effective delivery rate sufficient to provide an antianginally effective concentration of nitrate in the blood stream of the patient; and (3) thereafter, during a ramp-up delivery period, delivers the nitrate at an increasing rate until a final delivery rate is achieved, which is from 125% to 1,000% of the initial effective delivery rate. At the end of the ramp-up period, delivery is exhausted or otherwise terminated. A new unit dose is administered at bedtime, and the cycle is repeated. A preferred transdermal patch for carrying out the treatment is provided. Excerpt(s): The present invention relates to the treatment of patients having angina pectoris, particularly the form known as chronic, stable angina pectoris. ... Nitroglycerine (also commonly referred to as trinitroglycerine or glycerine trinitrate, and often referred to hereinafter by its common abbreviation, (TNG) has been used to treat angina pectoris for over 100 years. Nitroglycerine (TNG) and other organic nitrates have been available for the treatment of angina and congestive heart failure in a number of different dosage forms for some time. These include sublingual, oral and buccal tablets as well as capsules, topical creams and ointments, patches, tapes, inhalable sprays and intravenous solutions. Transdermal nitroglycerine patches were introduced in recent years in an effort to overcome some of the disadvantages and inconveniences of other dosage forms. In particular, they were formulated to provide increased systemic bioavailability as well as constant delivery of the drug over a 24 hour period or longer. They have become popular in the

88 Angina

treatment of chronic, stable angina. Typically, the patches are applied once daily, either in the morning or evening, and changed daily at approximately the same time. ... (2) "Nitrate Therapy for Angina Pectoris", Steven Corwin, MD, James A. Reiffel, MD, Arch Intern. Med., Vol. 145, Mar. 1985, pages 538-543. After reviewing the efficacy and mechanism of action of various nitrate preparations, the authors state that it is a matter of debate whether tolerance develops in patients receiving nitrates over long time periods, but suggest that the clinician should be aware of this possibility when using these agents. Web site: http://www.delphion.com/details?pn=US04956181__ ·

Method for treatment of angina and myocardial infarctions with omental lipids Inventor(s): Catsimpoolas; Nicholas (Newton Centre, MA), Gavras; Haralambos (Wayland, MA), Haudenschild; Christian C. (Newtonville, MA), Klibaner; Michael I. (Brookline, MA) Assignee(s): Trustees of Boston University (Boston, MA), Angio-Medical Corporation (New York, NY) Patent Number: 4,778,787 Date filed: December 20, 1985 Abstract: Angiogenesis healing factors residing in omentum-derived lipid fractions with or without gangliosides or their synthetic equivalents can be used to treat myocardial ischemic conditions including but not limited to myocardial infarction, angina, as well as in heart transplant, vascular grafts, and re-opened vessels leading to improved vascularization, perfusion, collagenization and organization of said lesions; the involved and adjacent tissues. Excerpt(s): Angiogenesis healing factor(s) residing in an omentumderived lipid fraction are used to treat myocardial ischemic conditions including but not limited to myocardial infarction (MI), angina, heart transplants and hearts with vascular grafts or recanalized coronary arteries with the purpose of improving vascularization, perfusion and organization of the involved and adjacent tissues. ... 2. Treatment of general myocardial ischemia (angina) by permanent increase of overall vascularization and collateralization allowing improved myocardial perfusion. Web site: http://www.delphion.com/details?pn=US04778787__

Patents 89

Patent Applications on Angina As of December 2000, U.S. patent applications are open to public viewing.25 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years). The following patent applications have been filed since December 2000 relating to angina: ·

Method for treating angina Inventor(s): Wolff, Andrew A. ; (San Francisco, CA), Blackburn, Brent K. (Los Altos, CA) Correspondence: A. Blair Hughes; McDonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20020052377 Date filed: July 20, 2001 Abstract: A method for administering a ranolazine dosage formulations to treat patients suffering from angina who are also suffering from a second complication or disease such a heart disease and diabetes and also to reduce myocardial infarct size wherein the infarct is the result of an ischemic event. Excerpt(s): This invention relates to methods for using ranolazine dosage formulations to treat patients suffering from angina who are also suffering from a second complication or disease such a heart disease and diabetes. This invention also relates to a method for reducing myocardial infarct size by administering ranolazine to a mammal prophalactically or by administering ranolazine to a mammal suffering from a heart attack. ... U.S. Pat. No. 4,567,264, the specification of which is incorporated herein by reference, discloses ranolazine, (.+-.)-N-(2,6-dimethylphenyl)-- 4-[2hydroxy-3-(2-methoxyphenoxy)-propyl ]-1-piperazineacetamide, and its pharmaceutically acceptable salts, and their use in the treatment of cardiovascular diseases, including arrhythmias, variant and exerciseinduced angina, and myocardial infarction. ... It was recently discovered that ranolazine can be used to treat angina in humans for a sustained period of time. See U.S. patent application Ser. Nos. 09/520,932, 09/321,522, and 09/538,337, the specifications of each of which are incorporated herein by reference. However, it remains uncertain whether or not ranolazine has additional therapeutic benefits or whether or not ranolazine can be used to treat patients suffering from angina and a second disease which might be detrimentally impacted ranolazine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

25

This has been a common practice outside the United States prior to December 2000.

90 Angina

·

Methods for treating hypertension and angina using salts of optically pure (-) amplodipine Inventor(s): Young, James W. ; (Palo Alto, CA) Correspondence: Pennie and Edmonds; 1155 Avenue of the Americas; New York; NY; 100362711 Patent Application Number: 20010029260 Date filed: April 24, 2001 Abstract: Methods and compositions are disclosed utilizing the optically pure (-) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. The (-) isomer of amlodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist such as cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure, without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. Excerpt(s): This invention relates to novel compositions of matter containing optically pure (-) amlodipine. These compositions possess potent activity in treating both systolic and diastolic hypertension while avoiding adverse effects including but not limited to edema of the extremities, headache and dizziness, which are associated with administration of the racemic mixture of amlodipine. Additionally, these novel compositions of matter containing optically pure (-) amlodipine are useful in treating angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure--while avoiding the adverse effects associated with administration of the racemic mixture of amlodipine. Also disclosed are methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of amlodipine, by administering the (-) isomer of amlodipine to said human. ... Furthermore, the racemic mixture of amlodipine is useful in treating other disorders such as angina pectoris. ... Angina pectoris is a highly variable, rather poorly understood clinical syndrome reflecting a myocardial ischemia. When cardiac work or myocardial oxygen demand exceeds the ability of the coronary arterial

Patents 91

vascular system to supply oxygen, the resulting ischemia stimulates the sensory nerves of the heart, producing the sensation of angina characterized by episodes of precordial pressure, discomfort, or a severe, intense crushing pain which may radiate to several sites including the left shoulder and left arm. Physical activity or exertion characteristically initiates the condition, and rest or drug therapy relieves the condition. The signs and symptoms of an episode persist for a few minutes, but can be induced or exaggerated by a meal or exposure to cold air. Treatment is directed to the underlying disease, usually atherosclerosis, or to drugs which either reduce myocardial oxygen demand or improve oxygen supply. Calcium antagonists such as amlodipine have been particularly useful in treating vasospastic angina, the angina of effort, and the unstable angina, due to the effect of the calcium channel antagonist on cardiac and vascular smooth muscle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with angina, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “angina” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on angina. You can also use this procedure to view pending patent applications concerning angina. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU]

92 Angina

Antihypertensive: An agent that reduces high blood pressure. [EU] Betablocker: A drug that induces adrenergic blockade at either ß1- or ß2adrenergic receptors or at both. [EU] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Dorsal: 1. pertaining to the back or to any dorsum. 2. denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Edema: Abnormal fluid accumulation in body tissues. [NIH] Epigastric: Pertaining to the epigastrium. [EU] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Medicament: A medicinal substance or agent. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Precordial: Pertaining to the precordium (= region over the heart and lower part of the thorax). [EU]

Patents 93

Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Solvent: 1. dissolving; effecting a solution. 2. a liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU]

Books 95

CHAPTER 6. BOOKS ON ANGINA Overview This chapter provides bibliographic book references relating to angina. You have many options to locate books on angina. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on angina include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “angina” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on angina:

96 Angina

·

Coronary artery disease in women: What all physicians need to know Source: Philadelphia, PA: American College of Physicians: American Society of Internal Medicine. 1999. 615 pp. Contact: Available from American College of Physicians-American Society of Internal Medicine, 190 North Independence Mall West, Philadelphia, PA 19106. Telephone: (215) 351-2400 or (800) 523-1546 / fax: (215) 351- 2799 / e-mail: [email protected] / Web site: http://www.acponline.org. $43 for nonmembers, $32 for members; plus shipping and handling. Summary: This book for health care practitioners reviews all important aspects of coronary artery disease, with an emphasis on gender differences, age, and race. It contains five parts: the introduction, prevention, diagnosis, management, and conclusion. The section on prevention discusses smoking; diabetes and insulin resistance; the history and pharmacologic management of lipids/cholesterol; nutrition; hypertension; obesity; exercise as prevention; aspirin, antioxidants, and alcohol; and issues in hormone replacement therapy. The diagnosis section provides information on the differential diagnosis of chest pain, noninvasive testing techniques, and influence of gender in coronary angiography. Topics in the the section on management include angina pectoris, acute coronary syndromes, bypass grafting risks, angioplasty, congestive heart failure, psychosocial issues, and pharmacologic secondary prevention. The concluding section discusses future trends in treatment and research. Each chapter contains a summary and list of references. Numerous charts and graphs present statistical information. The book concludes with an index.

·

Women's concise guide to a healthier heart Source: Cambridge, MA: Harvard University Press. 1997. 136 pp. Contact: Available from Harvard University Press, 79 Garden Street, Cambridge, MA 02138. Telephone: (800) 448-2242 or (617) 495-2600 / fax: (800) 962-4983. $12.95. Summary: This book for the general public focuses on recognizing and preventing heart diseases in women. It is divided into three parts. Part one defines the most common heart diseases such as angina pectoris, arrhythmia, coronary artery disease, heart failure, and heart valve disorders. The second part elaborates on other conditions that impact the heart's function. Topics include diabetes, high blood pressure, high cholesterol, obesity, and stroke. Part three discusses various ways of preventing or controlling heart disease, such as alcohol use, diet, estrogen

Books 97

replacement therapy, exercise, quitting smoking, stress reduction, and weight control. The book concludes with a resource listing and an index.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to angina (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

Angina Pectoris With Normal Coronary Arteries : Syndrome X (Developments in Cardiovascular Medicine, 152) by Juan Carlos Kaski (1994); ISBN: 0792326512; http://www.amazon.com/exec/obidos/ASIN/0792326512/icongroupin terna

·

Angina Pectoris: Management Strategies and Guide to Interventions (2nd Edition) by Thomas B. Graboys, Charles Blatt (1997); ISBN: 1884735118; http://www.amazon.com/exec/obidos/ASIN/1884735118/icongroupin terna

·

Beta-Blockers in Hypertension and Angina Pectoris : Different Compounds, Different Strategies by Ton J. M. Cleophas (1995); ISBN: 0792335163; http://www.amazon.com/exec/obidos/ASIN/0792335163/icongroupin terna

·

Cardiopulmonary Emergencies by Stephanie Forbes (1990); ISBN: 0874342694; http://www.amazon.com/exec/obidos/ASIN/0874342694/icongroupin terna

·

Chest Pain by Richard C. Becker (2000); ISBN: 0750671416; http://www.amazon.com/exec/obidos/ASIN/0750671416/icongroupin terna

·

Ischaemic Heart Disease (Current Status of Clinical Cardiology) by Kim M. Fox (Editor) (1987); ISBN: 0852008716; http://www.amazon.com/exec/obidos/ASIN/0852008716/icongroupin terna

98 Angina

·

Living With Angina : A Practical Guide to Dealing With Coronary Artery Disease and Your Doctor by James A. Pantano (1990); ISBN: 0060162406; http://www.amazon.com/exec/obidos/ASIN/0060162406/icongroupin terna

·

Silent Myocardial Ischemia and Angina : Prevalence, Prognostic, and Therapeutic Significance by Bramah Singh (1989); ISBN: 0080360785; http://www.amazon.com/exec/obidos/ASIN/0080360785/icongroupin terna

·

Therapy of Angina Pectoris : A Comprehensive Guide for the Clinician (Basic and Clinical Cardiology Series, Vol 8) by Donald A. Weiner, William H. Frishman (Editor) (1986); ISBN: 0824775368; http://www.amazon.com/exec/obidos/ASIN/0824775368/icongroupin terna

·

Unstable Angina by W. Bleifeld, et al (1990); ISBN: 0387520317; http://www.amazon.com/exec/obidos/ASIN/0387520317/icongroupin terna

·

Unstable Angina : A Clinical Approach by Plotnick (1985); ISBN: 0879932325; http://www.amazon.com/exec/obidos/ASIN/0879932325/icongroupin terna

·

Unstable Angina : Diagnosis and Management (Clinical Practice Guidelines Series, 10) by Michael H. Crawford (Preface), United States agency (1997); ISBN: 0412097710; http://www.amazon.com/exec/obidos/ASIN/0412097710/icongroupin terna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “angina” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:26 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the

26

Books 99

·

Angina: the disease state management resource. Author: editor, Dorothy Pennachio; Year: 1998; Atlanta, GA (3525 Piedmont Rd., NE, Atlanta 30305): American Health Consultants, [1998?]

·

Angina. Author: Graham Jackson; Year: 2000; London: M. Dunitz, 2000; ISBN: 1853176265 http://www.amazon.com/exec/obidos/ASIN/1853176265/icongroupin terna

·

Asymptomatic coronary artery disease & angina. Author: edited by John Cleland; with contributions from David Wood ... [et al.]; Year: 1996; London [England]: Science Press, c1996; ISBN: 1858731127 http://www.amazon.com/exec/obidos/ASIN/0896034348/icongroupin terna

·

Coronary revascularisation in the management of stable angina pectoris. A national clinical guideline. Scottish Intercollegiate Guidelines Network. Author: Burnett, J. Compton (James Compton), 1840-1901?; Year: 1998; Edinburgh, Scotland: SIGN, 1998; ISBN: 1899893563

·

Dalteparin and enoxaparin for unstable angina and non-Q-wave myocardial infarction: update. Author: [Tricia Nicholson, Ruairidh Milne, Ken Stein]; Year: 2000; Bristol, UK: South and West Regional Health Authority, 2000

·

Diagnosis and managing unstable angina. Author: Eugene Braunwald ... [et al.]; Year: 1996; [Rockville, Md?]: U.S. Dept. of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, National Heart, Lung, and Blood Institute, [1996]

·

Efficacy, effectiveness, and cost analysis of nitrate therapy for the prevention of angina pectoris. Author: Holbrook A.M. ... [et al.]; Year: 1996; [Canada]: Canadian Coordinating Office for Health Technology Assessment, [1996]; ISBN: 1895561396

·

Evaluation of beta-blockers, calcium antagonists, nitrates, and alternative therapies for stable angina. Author: prepared by University of California, San Francisco-Stanford, Paul A. Heidenreich, principal investigator; Kathryn McDonald ... [et al.]; Year: 1999; Rockville, MD: U.S. Dept. of Health and Human Services, Public Health Service, Agency for Healthcare Research and Quality, [1999]; ISBN: 1587630060

links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

100 Angina

·

Health care guideline: diagnosis of chest pain. Author: Institute for Clinical Systems Improvement; Year: 2000; Bloomington, MN: ICSI, 2000

·

Health technology review: the efficacy and effectiveness of sustained release oral nitroglycerin in comparison to regular delivery isosorbide dinitrate for the prophylactic treatment of stable angina pectoris. Author: K. Bassett, M. L. Rhone; Year: 1994; Vancouver, British Columbia, Canada: BCOHTA CHSPR, 1994; ISBN: 1896256015

·

Key advances in the effective management of unstable angina. Author: edited by J. Ferguson and H. Purcell; Year: 1999; London: Royal Society of Medicine Press, c1999; ISBN: 1853153915

·

Low molecular weight heparins (dalteparin and enoxaparin) compared with unfractionated heparin for unstable angina and non-Q-wave myocardial infarction. Author: T. Nicholson, K. Stein; Year: 1999; Bristol, UK: South and West Regional Health Authority, 1999

·

Management of angina and hypertension in patients with left ventricular dysfunction: focus on amlodipine. Author: edited by John McMurray; Year: 1998; London; New York, NY: Royal Society of Medicine Press, c1998; ISBN: 1853153346

·

Management of stable angina: a national clinical guideline. Author: Scottish Intercollegiate Guidelines Network; Year: 2001; Edinburgh, Scotland: SIGN, 2000

·

Management of stable angina. Author: M. Sculpher ... [et al.]; Year: 1997; York: NHS Centre for Reviews and Dissemination, 1997

·

Prediction of risk for patients with unstable angina. Author: prepared by UCSF-Stanford Evidence-based Practice Center; Paul A. Heidenreich, principal investigator; Year: 2000; Rockville, MD: Agency for Healthcare Research and Quality, U.S. Dept. of Health and Human Services, [2000]; ISBN: 1587630125

·

Primary care management of stable angina. Author: North of England Evidence Based Guideline Development Project; Centre for Health Services Research, University of Newcastle upon Tyne; Year: 1999; Newcastle upon Tyne: Centre for Health Services Research, [1999]; ISBN: 1870399935

·

Revascularization procedures for the treatment of stable angina pectoris: a state of the art review: report submitted to the Ministre de la santé et des services sociaux du Québec. Author: Conseil d'évaluation des technologies de la santé du Québec; Year: 1996; Montréal, Québec: Le Conseil, [1996]; ISBN: 2550254635

·

Spinal cord stimulation II: an innovative method in the treatment of PVD and angina. Author: Svante Horsch, Luc Claeys, editors; Year:

Books 101

1995; Darmstadt: Steinkopff; Berlin; New York: Springer, 1995; ISBN: 3798510288 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/3798510288/icongroupin terna ·

Surgical transmyocardial laser revascularization for the palliation of intractable angina. Author: ECRI; Year: 2001; Plymouth Meeting, PA: ECRI, c2001

·

Unstable angina: diagnosis and management: commentary on the Agency for Health Care Policy and Research Clinical practice guidelines #10. Author: editor, Michael H. Crawford; Year: 1997; New York: Chapman & Hall, c1997; ISBN: 0412097710 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0412097710/icongroupin terna

·

Use of nitrates in chronic stable angina. Author: prepared by Christine Perras; Year: 1996; Ottawa, Ont.: Canadian Coordinating Office for Health Technology Assessment, [1996]

Chapters on Angina Frequently, angina will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with angina, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and angina using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “angina” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on angina: ·

All Chest Pain Is Not Heart Pain Source: in Janowitz, H.D. Indigestion: Living Better with Upper Intestinal Problems from Heartburn to Ulcers and Gallstones. New York, NY: Oxford University Press. 1992. p. 107-114. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $11.95 plus shipping and handling. ISBN: 019508554X.

102 Angina

Summary: This chapter on chest pain is from a book that offers advice on how to take care of and avoid the whole complex of disturbances categorized as indigestion. The author first differentiates the symptoms of anterior (frontal) chest pain (which arises from the esophagus) from true angina (pain arising from the heart). Esophageal pain has nothing to do with effort or walking or climbing stairs; it can occur at night while a person is at rest or even awaken the person from sleep; swallowing disorders can also cause this severe pain. The common esophageal causes of the chest pain that may imitate the angina of heart disease are gastroesophageal reflux of gastric acid into the esophagus; disturbances in the motility function of the esophagus; and irritable esophageal syndrome. The author considers each of these conditions, noting their symptoms, diagnosis, and treatment, and stressing that if the patient's electrocardiogram, stress testing, and angiogram are negative, their hearts are healthy and the patient's chest pain can be treated as reflux or esophageal pain. Since the treatment of reflux and other esophageal pain is usually successful, the author suggests a vigorous trial of all antireflux methods and acid blocking techniques before proceeding to tests for microvascular angina. ·

Women and Cardiovascular Disease Source: in Nutrition in General Practice: Giving Advice to Women. Seabrook, N. Oxford, England, Butterworth-Heinemann, pp. 50-72, 1997. Contact: Butterworth-Heinemann, Linacre House, Jordan Hill, Oxford OX2 8DP, England. INTERNET/EMAIL: http://www.bh.com. Summary: Women and Cardiovascular Disease, a chapter in Nutrition in General Practice: Giving Advice to Women, describes how coronary heart disease (CHD) presents in women, which risk factors are important, and the priorities to consider when giving dietary advice. CHD is still the most common cause of death in British men and women. Estrogen appears to protect women from CHD until menopause. Women present with CHD (1) 5 to 10 years later than men; (2) more likely with angina than with an infarction; and (3) more likely with diabetes, hypertension, and heart failure. When women do present with an infarction, they often have a hard recovery with greater risk of death, recurrent infarctions, and stroke. Total cholesterol may be a risk factor for CHD in women, but because of conflicting data, the relationship between cholesterol and CHD in women is not yet known. Other risk factors of CHD in women are (1) low levels of high-density lipoproteins, (2) high triglycerides, (3) high blood pressure, (4) smoking, (5) obesity, and (6) high fibrinogen levels. CHD is thought to occur in three stages: (1) Arterial injury, prevented by antioxidants; (2) atherosclerosis, currently thought to be

Books 103

prevented by a balanced, varied diet; and (3) thrombosis, perhaps prevented by regular intake of oily fish. Specific areas of a patient's diet requiring dietary advice are (1) saturated fat intake, (2) vegetable oils, (3) fish oils, (4) cholesterol, (5) antioxidants, (6) trans-fatty acids, (7) fiber intake, (8) vitamin E, (9) red meat, (10) coffee, (11) olive oil, (12) butter, (13) eggs, and (14) alcohol. Women who have had a heart attack should receive advice immediately. The best, current advice is to eat a diet high in fish oil. The best advice for elderly patients is to eat a balanced diet and enjoy food. Some preliminary research shows that infants with low birthweight are more likely to develop CHD, hypertension, stroke, and diabetes later in life, perhaps because of poor nutrition during pregnancy. Thus, the current advice on preventing CHD in the future is proper nutrition during pregnancy. The chapter includes two case studies, sample menus for a healthy heart, and a CHD questionnaire. ·

Physical Activity and Diseases of the Cardiorespiratory System Source: in Aging, Physical Activity, and Health. Shephard, R.J. Champaign, IL, Human Kinetics, pp. 201-241, 1997. Contact: Human Kinetics, P.O. Box 5076, Champaign, IL 61825-5076. (800) 747-4457. INTERNET/EMAIL: http://www.humankinetics.com/; [email protected]. Summary: Physical Activity and Diseases of the Cardiorespiratory System, a chapter in Aging, Physical Activity, and Health, addresses the prevalence of and the role of physical activity in the prevention of ischemic heart disease, stroke, hypertension, peripheral vascular disease, congestive heart failure, end-stage renal disease, and chronic obstructive lung disease. It is now agreed that physical activity is helpful in primary and secondary prevention of ischemic heart disease in middle-aged adults. Research also shows that such exercise can improve longevity in all elderly persons, although, in the frail elderly person, physical activity may be harmful. Exercise is widely accepted as an important component in the tertiary treatment of angina, myocardial infarction, and even myocardial degeneration. In elderly persons, strokes are caused by obstructions of cerebral blood vessels. Research shows that exercise can play a role in primary and secondary prevention of strokes by controlling hypertension and hyperlipidemia. In the same manner, physical activity is a component in the prevention and improvement of peripheral vascular disease. Controlling diabetes and cigarette smoking must also occur. The effect of physical activity on congestive heart failure is hard to determine since many patients cannot exercise without complications. Primary prevention of congestive heart failure begins with controlling hypertension and ischemic heart disease before they lead to further

104 Angina

problems. Renal disease, the end result of hypertension or diabetes, severely limits exercise. Prevention of renal disease is directed at preventing its risk factors. The potential for primary prevention of chronic obstructive lung disease, in the form of bronchitis or emphysema, is limited, since patients have sustained irreversible damage. ·

Cardiovascular Disease Source: in Physical Activity for Health and Fitness. Jackson, A.W.; Morrow, J.R., Jr.; Hill, D.W.; Dishman, R.K. Champaign, IL, Human Kinetics, pp. 173-191, 1999. Contact: Human Kinetics, P.O. Box 5076, Champaign, IL 61825-5076. (800) 747-4457. Internet/Email: [email protected]. Summary: Cardiovascular Disease, a chapter in Physical Activity for Health and Fitness, looks at cardiovascular disease, which is the leading cause of death in the United States. It explores the causes and risk factors of the disease and distinguishes between the factors that cannot be changed and those that can be changed. The chapter also discusses how to prevent cardiovascular disease by working on the factors that can be changed and notes how physical activity affects the disease. It presents statistics on cardiovascular disease, and explains the cardiovascular system. The chapter presents the types of cardiovascular diseases and conditions, focusing on (1) heart attack, (2) atherosclerosis, (3) angina pectoris, (4) arrhythmia, (5) congenital heart defects, (6) rheumatic heart failure, (7) congestive heart failure, (8) bacterial endocarditis, (9) aneurysms, (10) hypertension, and (11) stroke. Risk factors for coronary heart disease and stroke that cannot be changed include heredity, gender, and age. Those that can be altered include (1) high blood pressure, (2) high blood cholesterol, (3) smoking, (4) diabetes, (5) obesity, and (6) physical inactivity. Contributing risk factors for coronary heart disease include excessive and prolonged stress. This chapter contains health checks (brief questions with immediate answers), highlighted key points, and a laboratory to reinforce its information. The laboratory experience focuses on evaluating the risks of heart attack.

·

Cardiovascular Diseases: Understanding Risks and Measures of Prevention Source: in Essentials for Health and Wellness. Edlin, G.; Golanty, E.; Brown, K.M. Sudbury, MA, Jones and Bartlett Publishers. pp. 201-215, 1997.

Books 105

Contact: Jones and Bartlett Publishers, 40 Tall Pine Drive, Sudbury, MA 01776. (508) 443-5000. INTERNET/EMAIL: http://www.jbpub.com; [email protected]. Summary: Cardiovascular Diseases: Understanding Risks and Measures of Prevention, a chapter in Essentials for Health and Wellness, describes briefly the functions of the heart, and then presents an in-depth discussion of the mechanism and causes of cardiovascular diseases both in general and for specific causes and diseases. Cardiovascular disease refers to any of a number of conditions that damage the heart or the arteries that carry blood to and from the heart. Arteriosclerosis includes all kinds of disease that damage the arteries, but the one that is of primary concern is atherosclerosis. This arterial disease begins with the formation of fibrous, fatty deposit called plaque. If the coronary arteries become partially blocked and the heart cells do not get enough oxygen, chest pain called angina pectoris results. In a heart attack, correct diagnosis is critical, if appropriate treatment is to be started. At present such a diagnosis is time consuming and costly. When medical tests such as an angiocardiography confirm that one or several coronary arteries are substantially blocked and that blood flow to the heart is restricted, various treatments are recommended. Stroke is a form of cardiovascular disease that affects arteries supplying blood to the brain. Strokes can result from injuries to the head or from weak spots in the arteries called aneurisms that balloon out and rupture. Among the risk factors for cardiovascular disease are heredity, sex, and age, none of which can be changed. However, other risk factors are controllable to some degree by the individual, including cholesterol intake, high blood pressure, smoking cigarettes, stress, physical inactivity, and poor dietary habits.

General Home References In addition to references for angina, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Heart Disease: Environment, Stress, and Gender by G. Weidner; Hardcover - 350 pages, Volume 327 (January 1, 2000), IOS Press; ISBN: 1586030825; http://www.amazon.com/exec/obidos/ASIN/1586030825/icongroupinterna · State Of The Heart by Larry W. Stephenson, M.D., et al; Paperback - 288 pages (January 30, 2000), Write Stuff Syndicate; ISBN: 0945903634; http://www.amazon.com/exec/obidos/ASIN/0945903634/icongroupinterna

106 Angina

· The HarperCollins Illustrated Medical Dictionary : The Complete Home Medical Dictionary by Ida G. Dox, et al; Paperback - 656 pages 4th edition (2001), Harper Resource; ISBN: 0062736469; http://www.amazon.com/exec/obidos/ASIN/0062736469/icongroupinterna · Mayo Clinic Guide to Self-Care: Answers for Everyday Health Problems by Philip Hagen, M.D. (Editor), et al; Paperback - 279 pages, 2nd edition (December 15, 1999), Kensington Publishing Corp.; ISBN: 0962786578; http://www.amazon.com/exec/obidos/ASIN/0962786578/icongroupinterna · The Merck Manual of Medical Information : Home Edition (Merck Manual of Medical Information Home Edition (Trade Paper) by Robert Berkow (Editor), Mark H. Beers, M.D. (Editor); Paperback - 1536 pages (2000), Pocket Books; ISBN: 0671027263; http://www.amazon.com/exec/obidos/ASIN/0671027263/icongroupinterna

Vocabulary Builder Alkalosis: A pathologic condition resulting from accumulation of base, or from loss of acid without comparable loss of base in the body fluids, and characterized by decrease in hydrogen ion concentration (increase in pH). [EU]

Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. The chief signs of arterial aneurysm are the formation of a pulsating tumour, and often a bruit (aneurysmal bruit) heard over the swelling. Sometimes there are symptoms from pressure on contiguous parts. [EU]

Angiocardiography: Radiography of the heart and great vessels after injection of a contrast medium. [NIH] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Arteritis: Inflammation of an artery. [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU]

Books 107

Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of lowdensity lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspnoea: Difficult or laboured breathing. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Emphysema: Chronic lung disease in which there is permanent destruction of alveoli. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Erythema: A name applied to redness of the skin produced by congestion of the capillaries, which may result from a variety of causes, the etiology or a specific type of lesion often being indicated by a modifying term. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [NIH] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU]

108 Angina

Hypotension: Abnormally low blood pressure. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Neuralgia: Paroxysmal pain which extends along the course of one or more nerves. Many varieties of neuralgia are distinguished according to the part affected or to the cause, as brachial, facial, occipital, supraorbital, etc., or anaemic, diabetic, gouty, malarial, syphilitic, etc. [EU] Pemphigus: A group of chronic, relapsing, sometimes fatal skin diseases characterized clinically by the development of successive crops of vesicles and bullae, histologically by acantholysis, and immunologically by serum autoantibodies directed against antigens in the intracellular zones of the epidermis. The specific disease is usually indicated by a modifying term; but the term pemphigus is often used alone to designate pemphigus vulgaris. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericoronitis: tooth. [NIH]

Inflammation of the gingiva surrounding the crown of a

Postural: Pertaining to posture or position. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder." [NIH] Ulcer: A local defect, or excavation, of the surface of an organ or tissue; which is produced by the sloughing of inflammatory necrotic tissue. [EU]

Multimedia 109

CHAPTER 7. MULTIMEDIA ON ANGINA Overview Information on angina can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on angina. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Bibliography: Multimedia on Angina The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in angina (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on angina. For more information, follow the hyperlink indicated: ·

Acute coronary syndromes : consensus before the next millennium. Source: Mayo Cardiovascular Division; a production of Mayo Audiovisual/Video Communications for the Mayo Clinic Cardiovascular Division; Year: 1997; Format: Videorecording; Rochester, Minn.: Mayo Foundation for Medical Education and Research, c1997

110 Angina

·

Acute coronary syndromes. Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1998; Format: Videorecording; Marshfield, WI: The Network, c1998

·

Advances in cardiology. Source: presented by Jay N. Cohn ... [et al.]; Year: 1987; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1987

·

Angina : current therapy. Source: HSN, Hospital Satellite Network; produced in cooperation with the American Journal of Nursing Co.; a production of Alvin H. Perlmutter, Inc; Year: 1984; Format: Videorecording; [Los Angeles, Calif.]: Hospital Satellite Network, c1984

·

Angina and silent ischemia : a clinical perspective. Source: [presented by] Ayerst; produced by Medical Education Programs, Ltd; Year: 1985; Format: Videorecording; New York, NY: Ayerst, c1985

·

Angina pectoris and hypertension. Source: a presentation of Films for the Humanities & Sciences; ITV, Information Television Network; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c2000

·

Angina pectoris, update on diagnosis & treatment. Source: [produced by Nicholas Dancy Productions, Inc.]; Year: 1984; Format: Videorecording; [Chicago, Ill.]: American Medical Association, c1984

·

Angina. Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983

·

Assessment & care of patients with angina. Source: produced by Classroom Productions, Inc; Year: 1997; Format: Videorecording; [San Luis Obispo, Calif.]: Classroom Productions, c1997

·

Cardiovascular emergencies. Source: produced by American Safety Video Publishers, produced in cooperation with Scott Bourn Associates, Inc. and American College of Emergency Physicians; Year: 1995; Format: Videorecording; [St. Louis, Mo.]: Mosby-Year Book, c1995

·

Chest pain. Source: a Hahnemann Medical College & Hospital and World Video Corp. production; Year: 1981; Format: Videorecording; [S.l.]: Analgesic CME Group, c1981

·

Coronary artery disease and angina pectoris. Source: [presented by] Blanchard & Loeb Publishers, LLC; Year: 2000; Format: Videorecording; [Glenmoore, PA]: Blanchard & Loeb Publishers, c2000

·

Diagnosis and treatment of angina. Source: [presented by] Audio-Video Digest Foundation ... in collaboration with the University of California, San Francisco, School of Medicine; [produced by] Shotwell Image Group;

Multimedia 111

Year: 1984; Format: Videorecording; Glendale, Calif.: The Foundation, c1984 ·

Management of angina pectoris following coronary artery bypass surgery. Source: [presented by] the Emory Medical Television Network, Emory University School of Medicine of the Robert W. Woodruff Health Sciences Center; Year: 1994; Format: Videorecording; Atlanta, GA: Emory University, c1994

·

Management of patients with unstable angina pectoris. Source: presented by the Department of Medicine, Emory University, School of Medicine [and] the Emory Medical Television Network; Year: 1988; Format: Videorecording; Atlanta, Ga.: The University, 1988

·

Medical and surgical management of angina pectoris. Source: [sponsored by the Veterans Administration]; Communications by Design; Year: 1980; Format: Videorecording; Washington, D.C.: National Audiovisual Center, [1980]

·

New therapeutic approaches for acute coronary syndromes. Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1998; Format: Videorecording; Marshfield, WI: The Network, c1998

·

Office management of angina pectoris. Source: produced in collaboration with Medical Department, Ives Laboratories Inc; Year: 1973; Format: Motion picture; [United States: Ives Laboratories, 1973]

·

Post infarction angina: use of vasodilators in CHF; Coronary artery spasm; Beta-blockers following acute myocardial infarction; Clues to unfavorable outcome following acute myocardial infarction: arrhythmias and left ventricular dysfunction [videorec. Year: 1986; Sarasota, Fla.: CMESAT, c1986

·

Prognostic and therapeutic implications of silent myocardial ischemia in unstable angina and acute infarction. Source: presented by the Department of Medicine, Emory University, School of Medicine; Year: 1986; Format: Videorecording; Atlanta, Ga.: The University, 1986

·

Stable and unstable angina pectoris. Source: presented by the Department of Medicine, Emory University, School of Medicine; Year: 1987; Format: Videorecording; Atlanta, Ga.: The University, 1987

·

Two patients with angina. Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983

·

Unstable angina . Year: 1985; Format: Slide; Columbus, OH: Center for Continuing Medical Education, the Ohio State University College of Medicine, 1985

112 Angina

·

Unstable angina syndrome. Source: Marshfield Clinic [and] Saint Joseph's Hospital; Year: 1993; Format: Videorecording; Marshfield, WI: The Clinic, [1993]

·

Unstable angina. Source: a co-production of Multimedia Communications and Physician Education and Development; Year: 2000; Format: Videorecording; Oakland, CA: Kaiser Permanente, c2000

·

What's new in the treatment of angina pectoris? Source: produced by John Davies; Year: 1987; Format: Videorecording; [Gwent: Medical Education Services], c1987

Physician Guidelines and Databases 113

CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common disorders, the National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

114 Angina

The NHLBI recently recommended the following guidelines and references to physicians treating patients with heart conditions: High Blood Pressure Information ·

Clinical Advisory Statement: Importance of Systolic Blood Pressure in Older Americans: http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbpstmt/index.htm

·

Working Group Report on High Blood Pressure in Pregnancy: http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_preg.htm

·

Statement from the National High Blood Pressure Education Program Coordinating Committee Regarding the Consumption of Dietary Salt: http://www.nhlbi.nih.gov/health/prof/heart/hbp/salt_upd.htm

·

Workshop on Sodium and Blood Pressure: http://www.nhlbi.nih.gov/health/prof/heart/hbp/salt_ws.htm

·

1999 Clinical Advisory: Treatment of Hypertension and Diabetes: http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_diab.htm

·

Your Guide to Lowering High Blood Pressure: http://www.nhlbi.nih.gov/hbp/index.html

·

The Sixth Report of the Joint National Committee (JNC VI) on High Blood Pressure: http://www.nhlbi.nih.gov/guidelines/hypertension/jncintro.htm

·

JNC VI Quick Reference Card: http://www.nhlbi.nih.gov/guidelines/hypertension/jnc6card.htm

·

Report on High Blood Pressure in Children and Adolescents: http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.htm

·

Implementing Recommendations for Dietary Salt Reduction: http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_salt.htm

·

Report on Primary Prevention of High Blood Pressure: http://www.nhlbi.nih.gov/health/prof/heart/hbp/pphbp.htm

·

Working Group Report on Ambulatory Blood Pressure Monitoring: http://www.nhlbi.nih.gov/health/prof/heart/hbp/abpm.txt

·

Working Group Report on Hypertension in Diabetes: http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbpdiab.txt

·

National High Blood Pressure Education Program (NHBPEP): http://www.nhlbi.nih.gov/about/nhbpep/index.htm

·

High Blood Pressure Information Slide Sets: http://hin.nhlbi.nih.gov/nhbpep_slds/menu.htm

Physician Guidelines and Databases 115

Cholesterol Information ·

Clinical Guidelines on Cholesterol Management in Adults (ATP III): http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm

·

Recommendations on Lipoprotein Measurement: http://www.nhlbi.nih.gov/health/prof/heart/chol/lipoprot.htm

·

Cholesterol Education Month Kit: http://hin.nhlbi.nih.gov/cholmonth/

·

Recommendations Regarding Public Screening for Measuring Blood Cholesterol: http://www.nhlbi.nih.gov/guidelines/cholesterol/chol_scr.htm

·

National Cholesterol Education Program (NCEP): http://www.nhlbi.nih.gov/about/ncep/index.htm Obesity Information

Clinical guidelines on overweight and obesity: ·

Full Report (the Guidelines): http://www.nhlbi.nih.gov/guidelines/obesity/ob_home.htm

·

Electronic Textbook: http://www.nhlbi.nih.gov/guidelines/obesity/e_txtbk/index.htm

·

The Practical Guide: http://www.nhlbi.nih.gov/guidelines/obesity/practgde.htm

·

Slide Set: http://hin.nhlbi.nih.gov/oei_ss/menu.htm

·

Guidelines in Palm OS Format: http://hin.nhlbi.nih.gov/obgdpalm.htm

·

BMI Calculator in Palm OS Format: http://hin.nhlbi.nih.gov/bmi_palm.htm

Other publications: ·

Strategy Development Workshop for Public Education on Weight and Obesity: http://www.nhlbi.nih.gov/health/prof/heart/obesity/wtob.txt

·

FDA information on new preliminary recommendations from the U.S. Department of Health and Human Services regarding the medical management of people who took the diet drugs fenfluramine or dexfenfluramine: http://www.fda.gov/cder/news/feninfo.htm

·

NHLBI Obesity Education Initiative (OEI): http://www.nhlbi.nih.gov/about/oei/index.htm

116 Angina

·

Hearts N' Parks: http://www.nhlbi.nih.gov/health/prof/heart/obesity/hrt_n_pk/index.htm

·

The Surgeon General's Call to Action for Overweight and Obesity: http://www.surgeongeneral.gov/topics/obesity Heart Attack Information

Act in Time to Heart Attack Signs materials: ·

Act in Time to Heart Attack Signs Web Page: http://www.nhlbi.nih.gov/actintime/index.htm

·

Brochure--English: http://www.nhlbi.nih.gov/health/public/heart/mi/core_bk.htm

·

Wallet Card: http://www.nhlbi.nih.gov/health/public/heart/mi/wallet.htm

·

Poster: http://www.nhlbi.nih.gov/health/public/heart/mi/poster.htm

·

Patient Action Plan Tablet: http://www.nhlbi.nih.gov/health/public/heart/mi/act_plan.htm

·

Physician Quick Reference Tool for Palm OS: http://hin.nhlbi.nih.gov/haac_palm/haac_palm.htm

·

Physician Quick Reference Card: http://www.nhlbi.nih.gov/health/prof/heart/mi/provider.htm

· Video: http://www.nhlbi.nih.gov/health/prof/heart/mi/aitvideo.htm Other publications: ·

Symposium Proceedings: New Information Technology and the NHAAP: http://www.nhlbi.nih.gov/health/prof/heart/mi/ha_tech.htm

·

Informatics for the National Heart Attack Alert Program--Descriptions of Projects: http://www.nlm.nih.gov/ep/nhaap.html Rapid Identification and Treatment of Acute Myocardial Infarction

·

Staffing and Equipping Emergency Medical Service Systems: http://www.nhlbi.nih.gov/health/prof/heart/mi/staffing.htm

·

911: http://www.nhlbi.nih.gov/health/prof/heart/mi/911.htm

·

Emergency Medical Dispatching: http://www.nhlbi.nih.gov/health/prof/heart/mi/emd.htm

Physician Guidelines and Databases 117

·

Emergency Department: http://www.nhlbi.nih.gov/health/prof/heart/mi/emerdept.txt

·

Patient/Bystander Recognition and Action: http://www.nhlbi.nih.gov/health/prof/heart/mi/bystand.txt

·

An Evaluation of Technologies for Identifying Acute Cardiac Ischemia in the Emergency Departments: http://www.nhlbi.nih.gov/about/nhaap/twg.htm

·

Educational Strategies to Prevent Prehospital Delay in High Risk Patients: http://www.nhlbi.nih.gov/about/nhaap/highrisk.htm

·

Exploring the Issues: AMI/ACI in Managed Care: http://www.nhlbi.nih.gov/about/nhaap/mangcare.htm

·

National Heart Attack Alert Program (NHAAP): http://www.nhlbi.nih.gov/about/nhaap/index.htm Other Cardiovascular Information

·

Strong Heart Study Data Book: http://www.nhlbi.nih.gov/resources/docs/shs_db.htm

Developing a Women's Heart Health Education Action Plan: ·

Web Page: http://hin.nhlbi.nih.gov/womencvd/

·

Workshop Report: http://www.nhlbi.nih.gov/health/prof/heart/other/whhw.htm

Asian American and Pacific Islander Action Plan: ·

The Impact of Heart Disease on Asian Americans and Pacific Islanders Online Slide Show: http://hp2010.nhlbihin.net/aapi_slds/menu.htm

·

Asian American and Pacific Islander Workshops Summary Report on Cardiovascular Health: http://www.nhlbi.nih.gov/health/prof/heart/other/aapi_sum.htm

·

Addressing Cardiovascular Health in Asian American and Pacific Islanders: Background Report: http://www.nhlbi.nih.gov/health/prof/heart/other/aapibkgd/index.htm

Other publications: ·

Latino Cardiovascular Health Resources: http://www.nhlbi.nih.gov/health/prof/heart/latino/latin_pg.htm

118 Angina

·

Building Healthy Hearts for American Indians and Alaska Natives: Background Paper: http://www.nhlbi.nih.gov/health/prof/heart/other/na_bkgd.htm

·

Report on Research in Coronary Heart Disease in Blacks: http://www.nhlbi.nih.gov/health/prof/heart/other/r_chdblk.htm

·

Working with Religious Congregations: http://www.nhlbi.nih.gov/health/prof/heart/other/church.htm

·

JumpSTART (Activities to Promote Healthy Lifestyles for Grades Three to Five): http://www.nhlbi.nih.gov/health/prof/heart/other/jumpstrt.htm

·

HeartMemo: http://www.nhlbi.nih.gov/health/prof/heart/other/hrtmemo.htm

·

NHLBI Stroke Belt Initiative: http://www.nhlbi.nih.gov/health/prof/heart/other/sb_spec.htm Additional Resources

·

Cardiovascular Information for Patients and the General Public: http://www.nhlbi.nih.gov/health/public/heart/index.htm

·

List of Publications: http://www.nhlbi.nih.gov/health/pubs/index.htm

·

Join the Health Information Network: http://emall.nhlbihin.net/hp2010/

·

Information Center: http://www.nhlbi.nih.gov/health/infoctr/index.htm

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.27 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:28 ·

Bioethics: Access to published literature on the ethical, legal and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 28 See http://www.nlm.nih.gov/databases/databases.html. 27

Physician Guidelines and Databases 119

Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html ·

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

·

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

·

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

·

Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

·

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

·

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

·

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

·

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

·

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

120 Angina

·

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

·

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

While all of the above references may be of interest to physicians who study and treat angina, the following are particularly noteworthy.

The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and angina using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By making these selections and typing “angina” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with angina.

The NLM Gateway29 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM’s information resources or databases.30 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families,

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

29 30

Physician Guidelines and Databases 121

and the public.31 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “angina” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Items Found Journal Articles 39608 Books / Periodicals / Audio Visual 695 Consumer Health 149 Meeting Abstracts 86 Other Collections 19 Total 40557

HSTAT32 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.33 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.34 Simply search by “angina” (or synonyms) at the following Web site: http://text.nlm.nih.gov. Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 32 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 33 The HSTAT URL is http://hstat.nlm.nih.gov/. 34 Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention 31

122 Angina

Coffee Break: Tutorials for Biologists35 Some patients may wish to have access to a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. To this end, we recommend “Coffee Break,” a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.36 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.37 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

·

Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

(SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force’s Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 35 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 36 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 37 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

Physician Guidelines and Databases 123

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

·

MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

·

Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see the following Web site: http://www.lexical.com/Metaphrase.html.

The Genome Project and Angina With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to angina. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).38 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “angina” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and 38 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

124 Angina

databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for angina: ·

Apolipoprotein A-i; Apoa1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?107680

·

Apolipoprotein E Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?107741

·

Arrhythmogenic Right Ventricular Dysplasia, Familial, 1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?107970

·

Berardinelli-seip Congenital Lipodystrophy Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?269700

·

Cerebrotendinous Xanthomatosis Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?213700

·

Cytochrome P450, Subfamily Iid Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?124030

·

Fabry Disease Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?301500

·

Heparin Cofactor Ii Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?142360

·

Homocystinuria Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?236200

·

Integrin, Beta-3 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?173470

Physician Guidelines and Databases 125

Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by the system of the body associated with it. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, Atherosclerosis, Best disease, Gaucher disease, Glucose galactose malabsorption, Gyrate atrophy, Juvenile onset diabetes, Obesity, Paroxysmal nocturnal hemoglobinuria, Phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

·

Nervous System: Mind and body. Examples: Alzheimer disease, Amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, Fragile X syndrome, Friedreich’s ataxia, Huntington disease, NiemannPick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, Spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

·

Transporters: Pumps and channels. Examples: Cystic Fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html

126 Angina

Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

·

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genom e, and then select the database that you would like to search. The databases

Physician Guidelines and Databases 127

available are listed in the drop box next to “Search.” In the box next to “for,” enter “angina” (or synonyms) and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database39 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At the following Web site you can also search across syndromes using an alphabetical index: http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html. You can search by keywords at this Web site: http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database40 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 40 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission. 39

128 Angina

“angina” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to non-professionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.

Specialized References The following books are specialized references written for professionals interested in angina (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · Cardiology in Primary Care by William T. Branch (Editor), et al; Hardcover - 940 pages, 1st edition (April 15, 2000), McGraw-Hill Professional Publishing; ISBN: 0070071624; http://www.amazon.com/exec/obidos/ASIN/0070071624/icongroupinterna · Clinical Cardiology : An Illustrated Text by Kanu Chaterjee, G. Sutton (Contributor); Hardcover - 431 pages, 2nd Revised edition (December 15, 1998), Lippincott, Williams & Wilkins Publishers; ISBN: 041278310X; http://www.amazon.com/exec/obidos/ASIN/041278310X/icongroupinterna · Current Pocket Reference, 2000, Cardiology by Larry Shepherd, et al; Hardcover, 1st edition (December 15, 2001), Springer Verlag; ISBN: 0964219360; http://www.amazon.com/exec/obidos/ASIN/0964219360/icongroupinterna · The Heart: Physiology, from Cell to Circulation by Lionel H. Opie; Hardcover - 544 pages, 3rd edition (April 1998), Lippincott, Williams & Wilkins Publishers; ISBN: 078171560; http://www.amazon.com/exec/obidos/ASIN/0781715601/icongroupinterna · Heart Disease in Primary Care (Primary Care Series) by Michael L. Hess (Editor), Andrea Hastillo (Editor); Paperback - 376 pages (January 15, 1999), Lippincott, Williams & Wilkins; ISBN: 0683039881; http://www.amazon.com/exec/obidos/ASIN/0683039881/icongroupinterna

Vocabulary Builder Arrhythmogenic: Producing or promoting arrhythmia. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal

Physician Guidelines and Databases 129

surface of the colon. [NIH] Dexfenfluramine: A serotonin agonist drug used to treat obesity. FDA approval has been withdrawn. [NIH] Dysplasia: Abnormal development or growth. [NIH] Fenfluramine: A serotonin agonist drug used in the treatment of obesity. FDA approval has been withdrawn. [NIH] Immunization: Protection from disease by administering vaccines that induce the body to form antibodies against infectious agents. [NIH] Lipodystrophy: 1. any disturbance of fat metabolism. 2. a group of conditions due to defective metabolism of fat, resulting in the absence of subcutaneous fat, which may be congenital or acquired and partial or total. Called also lipoatrophy and lipodystrophia. [EU] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Xanthomatosis: A condition of morphologic change in which there is accumulation of lipids in the large foam cells of tissues. It is the cutaneous manifestation of lipidosis in which plasma fatty acids and lipoproteins are quantitatively changed. The xanthomatous eruptions have several different distinct morphologies dependent upon the specific form taken by the disease. [NIH]

Dissertations 131

CHAPTER 9. DISSERTATIONS ON ANGINA Overview University researchers are active in studying almost all known disorders and conditions. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to angina. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Angina ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to angina. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with angina: ·

Differences in Personality Characteristics and Compliance to an Exercise Program for Patients with Myocardial Infarction and Angina Pectoris by Allen, Scott William, PhD from The University of North Carolina at Chapel Hill, 1985, 147 pages http://wwwlib.umi.com/dissertations/fullcit/8527176

132 Angina

·

Heart Rate Variability Analysis in Unstable Angina by Gonzalez Hernandez, Enrique; PhD from Universitat De Valencia (spain), 2000, 196 pages http://wwwlib.umi.com/dissertations/fullcit/f1159169

Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to angina is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

133

PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with angina and related conditions.

Researching Your Medications 135

APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with angina. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for angina. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of angina. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

136 Angina

Your Medications: The Basics41 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of angina. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with angina take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment you might receive.

·

Ask how often you or your doctor will check for side effects from a given medication.

Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for angina. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to take the medicine, how much to take, and for how long.

·

What food, drinks, other medicines, or activities you should avoid while taking the medicine.

·

What side effects the medicine may have, and what to do if they occur.

·

If you can get a refill, and how often.

41

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

Researching Your Medications 137

·

About any terms or directions you do not understand.

·

What to do if you miss a dose.

·

If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell your doctor about all the medicines you are currently taking (not just those for angina). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for angina. One such source is

138 Angina

the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database.42 While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of angina. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to angina: Amlodipine ·

Systemic - U.S. Brands: Norvasc http://www.nlm.nih.gov/medlineplus/druginfo/amlodipinesyste mic202670.html

Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

42

Researching Your Medications 139

Beta-Adrenergic Blocking Agents ·

Systemic - U.S. Brands: Betapace; Blocadren; Cartrol; Corgard; Inderal; Inderal LA; Kerlone; Levatol; Lopressor; Normodyne; Sectral; Tenormin; Toprol-XL; Trandate; Visken; Zebeta http://www.nlm.nih.gov/medlineplus/druginfo/betaadrenergicb lockingagentssy202087.html

Calcium Channel Blocking Agents ·

Systemic - U.S. Brands: Adalat; Adalat CC; Calan; Calan SR; Cardene; Cardizem; Cardizem CD; Cardizem SR; Dilacor-XR; DynaCirc; Isoptin; Isoptin SR; Nimotop; Plendil; Procardia; Procardia XL; Vascor; Verelan http://www.nlm.nih.gov/medlineplus/druginfo/calciumchannel blockingagentssy202107.html

Enoxaparin ·

Systemic - U.S. Brands: Lovenox http://www.nlm.nih.gov/medlineplus/druginfo/enoxaparinsyste mic202686.html

Nitrates Lingual Aerosol ·

Systemic - U.S. Brands: Nitrolingual http://www.nlm.nih.gov/medlineplus/druginfo/nitrateslinguala erosolsystemic202410.html

Nitrates Oral ·

Systemic - U.S. Brands: Dilatrate-SR; IMDUR; ISDN; ISMO; Isordil Tembids; Isordil Titradose; Monoket; Nitrocot; Nitroglyn E-R; Nitrong; Nitro-par; Nitro-time; Sorbitrate http://www.nlm.nih.gov/medlineplus/druginfo/nitratesoralsyste mic202411.html

Nitrates Sublingual, Chewable, or Buccal ·

Systemic - U.S. Brands: Isordil; Nitrogard; Nitrostat; Sorbitrate http://www.nlm.nih.gov/medlineplus/druginfo/nitratessublingu alchewableorbu202412.html

Nitrates Topical ·

Systemic - U.S. Brands: Deponit; Minitran; Nitro-Bid; Nitrodisc; Nitro-Dur; Nitrol; Transderm-Nitro http://www.nlm.nih.gov/medlineplus/druginfo/nitratestopicalsy stemic202413.html

140 Angina

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your doctor’s office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following medications are listed in the Reuters’ database as associated with angina (including those with contraindications):43 ·

Acebutolol HCl http://www.reutershealth.com/atoz/html/Acebutolol_HCl.htm

·

Albuterol http://www.reutershealth.com/atoz/html/Albuterol.htm

·

Alteplase Recombinant http://www.reutershealth.com/atoz/html/Alteplase_Recombinant.htm

·

Amiloride HCl http://www.reutershealth.com/atoz/html/Amiloride_HCl.htm

·

Amlodipine http://www.reutershealth.com/atoz/html/Amlodipine.htm

·

Amyl Nitrite http://www.reutershealth.com/atoz/html/Amyl_Nitrite.htm

·

Aspirin http://www.reutershealth.com/atoz/html/Aspirin.htm

·

Aspirin (Acetylsalicylic Acid; ASA) http://www.reutershealth.com/atoz/html/Aspirin_(Acetylsalicylic_Aci d;_ASA).htm

·

Atenolol http://www.reutershealth.com/atoz/html/Atenolol.htm

·

Basiliximab http://www.reutershealth.com/atoz/html/Basiliximab.htm

43

Adapted from A to Z Drug Facts by Facts and Comparisons.

Researching Your Medications 141

·

Betaxolol HCl http://www.reutershealth.com/atoz/html/Betaxolol_HCl.htm

·

Bisoprolol Fumarate http://www.reutershealth.com/atoz/html/Bisoprolol_Fumarate.htm

·

Bitolterol Mesylate http://www.reutershealth.com/atoz/html/Bitolterol_Mesylate.htm

·

Bivalirudin http://www.reutershealth.com/atoz/html/Bivalirudin.htm

·

Bretylium Tosylate http://www.reutershealth.com/atoz/html/Bretylium_Tosylate.htm

·

Carteolol HCl http://www.reutershealth.com/atoz/html/Carteolol_HCl.htm

·

Clofibrate http://www.reutershealth.com/atoz/html/Clofibrate.htm

·

Clozapine http://www.reutershealth.com/atoz/html/Clozapine.htm

·

Dalteparin Sodium http://www.reutershealth.com/atoz/html/Dalteparin_Sodium.htm

·

Diazoxide Parenteral http://www.reutershealth.com/atoz/html/Diazoxide_Parenteral.htm

·

Diltiazem HCl http://www.reutershealth.com/atoz/html/Diltiazem_HCl.htm

·

Enalapril Maleate http://www.reutershealth.com/atoz/html/Enalapril_Maleate.htm

·

Enoxaparin Sodium http://www.reutershealth.com/atoz/html/Enoxaparin_Sodium.htm

·

Ephedrine http://www.reutershealth.com/atoz/html/Ephedrine.htm

·

Esmolol HCl http://www.reutershealth.com/atoz/html/Esmolol_HCl.htm

·

Felodipine http://www.reutershealth.com/atoz/html/Felodipine.htm

·

Fluoxetine HCl http://www.reutershealth.com/atoz/html/Fluoxetine_HCl.htm

·

Formoterol Fumarate http://www.reutershealth.com/atoz/html/Formoterol_Fumarate.htm

142 Angina

·

Guanethidine Monosulfate http://www.reutershealth.com/atoz/html/Guanethidine_Monosulfate. htm

·

Hydralazine HCI http://www.reutershealth.com/atoz/html/Hydralazine_HCI.htm

·

Interferon beta-1a http://www.reutershealth.com/atoz/html/Interferon_beta-1a.htm

·

Ipratropium Bromide Albuterol Sulfate http://www.reutershealth.com/atoz/html/Ipratropium_Bromide_Albu terol_Sulfate.htm

·

Isoproterenol http://www.reutershealth.com/atoz/html/Isoproterenol.htm

·

Isosorbide Dinitrate http://www.reutershealth.com/atoz/html/Isosorbide_Dinitrate.htm

·

Isosorbide Mononitrate http://www.reutershealth.com/atoz/html/Isosorbide_Mononitrate.htm

·

Isradipine http://www.reutershealth.com/atoz/html/Isradipine.htm

·

Labetalol HCL http://www.reutershealth.com/atoz/html/Labetalol_HCL.htm

·

Latanoprost http://www.reutershealth.com/atoz/html/Latanoprost.htm

·

Levothyroxine Sodium http://www.reutershealth.com/atoz/html/Levothyroxine_Sodium.htm

·

Liothyronine Sodium http://www.reutershealth.com/atoz/html/Liothyronine_Sodium.htm

·

Lopinavir Ritonavir http://www.reutershealth.com/atoz/html/Lopinavir_Ritonavir.htm

·

Lovastatin http://www.reutershealth.com/atoz/html/Lovastatin.htm

·

Metaproterenol Sulfate http://www.reutershealth.com/atoz/html/Metaproterenol_Sulfate.htm

·

Methyldopa and Methyldopate HCl http://www.reutershealth.com/atoz/html/Methyldopa_and_Methyldo pate_HCl.htm

Researching Your Medications 143

·

Methylphenidate HCl http://www.reutershealth.com/atoz/html/Methylphenidate_HCl.htm

·

Metoprolol http://www.reutershealth.com/atoz/html/Metoprolol.htm

·

Mexiletine HCl http://www.reutershealth.com/atoz/html/Mexiletine_HCl.htm

·

Milrinone Lactate http://www.reutershealth.com/atoz/html/Milrinone_Lactate.htm

·

Minoxidil http://www.reutershealth.com/atoz/html/Minoxidil.htm

·

Mirtazapine http://www.reutershealth.com/atoz/html/Mirtazapine.htm

·

Nadolol http://www.reutershealth.com/atoz/html/Nadolol.htm

·

Naratriptan http://www.reutershealth.com/atoz/html/Naratriptan.htm

·

Nefazodone Hydrochloride http://www.reutershealth.com/atoz/html/Nefazodone_Hydrochloride. htm

·

Niacin http://www.reutershealth.com/atoz/html/Niacin.htm

·

Nicardipine HCL http://www.reutershealth.com/atoz/html/Nicardipine_HCL.htm

·

Nicotine http://www.reutershealth.com/atoz/html/Nicotine.htm

·

Nifedipine http://www.reutershealth.com/atoz/html/Nifedipine.htm

·

Nisoldipine http://www.reutershealth.com/atoz/html/Nisoldipine.htm

·

Nitroglycerin http://www.reutershealth.com/atoz/html/Nitroglycerin.htm

·

Omeprazole http://www.reutershealth.com/atoz/html/Omeprazole.htm

·

Oral Contraceptives Combination Products http://www.reutershealth.com/atoz/html/Oral_Contraceptives_Combi nation_Products.htm

144 Angina

·

Pantoprazole http://www.reutershealth.com/atoz/html/Pantoprazole.htm

·

Pantoprazole Sodium http://www.reutershealth.com/atoz/html/Pantoprazole_Sodium.htm

·

Papaverine HCl http://www.reutershealth.com/atoz/html/Papaverine_HCl.htm

·

Penbutolol Sulfate http://www.reutershealth.com/atoz/html/Penbutolol_Sulfate.htm

·

Pentoxifylline http://www.reutershealth.com/atoz/html/Pentoxifylline.htm

·

Phentolamine http://www.reutershealth.com/atoz/html/Phentolamine.htm

·

Phenylephrine HCl http://www.reutershealth.com/atoz/html/Phenylephrine_HCl.htm

·

Pindolol http://www.reutershealth.com/atoz/html/Pindolol.htm

·

Pirbuterol Acetate http://www.reutershealth.com/atoz/html/Pirbuterol_Acetate.htm

·

Propafenone http://www.reutershealth.com/atoz/html/Propafenone.htm

·

Propofol http://www.reutershealth.com/atoz/html/Propofol.htm

·

Propranolol HCl http://www.reutershealth.com/atoz/html/Propranolol_HCl.htm

·

Risperidone http://www.reutershealth.com/atoz/html/Risperidone.htm

·

Ritodrine HCl http://www.reutershealth.com/atoz/html/Ritodrine_HCl.htm

·

Rivastigmine Tartrate http://www.reutershealth.com/atoz/html/Rivastigmine_Tartrate.htm

·

Rizatriptan http://www.reutershealth.com/atoz/html/Rizatriptan.htm

·

Rofecoxib http://www.reutershealth.com/atoz/html/Rofecoxib.htm

·

Selegiline HCl http://www.reutershealth.com/atoz/html/Selegiline_HCl.htm

Researching Your Medications 145

·

Sildenafil http://www.reutershealth.com/atoz/html/Sildenafil.htm

·

Sumatriptan Succinate http://www.reutershealth.com/atoz/html/Sumatriptan_Succinate.htm

·

Tacrolimus http://www.reutershealth.com/atoz/html/Tacrolimus.htm

·

Thyroid Desiccated http://www.reutershealth.com/atoz/html/Thyroid_Desiccated.htm

·

Timolol Maleate http://www.reutershealth.com/atoz/html/Timolol_Maleate.htm

·

Tinzaparin Sodium http://www.reutershealth.com/atoz/html/Tinzaparin_Sodium.htm

·

Travoprost http://www.reutershealth.com/atoz/html/Travoprost.htm

·

Vasopressin http://www.reutershealth.com/atoz/html/Vasopressin.htm

·

Verapamil HCI http://www.reutershealth.com/atoz/html/Verapamil_HCI.htm

·

Zolmitriptan http://www.reutershealth.com/atoz/html/Zolmitriptan.htm

Mosby’s GenRx Mosby’s GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html. Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.

146 Angina

Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with angina--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat angina or potentially create deleterious side effects in patients with angina. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take.

Researching Your Medications 147

The package insert provides more information about potential drug interactions.

A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with angina. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with angina. The FDA warns patients to watch out for44: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)

·

Quick, painless, or guaranteed cures

·

If it sounds too good to be true, it probably isn’t true.

If you have any questions about any kind of medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Complete Guide to Prescription and Nonprescription Drugs 2001 (Complete Guide to Prescription and Nonprescription Drugs, 2001) by H. Winter Griffith, Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/039952634X/icongroupinterna

44

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

148 Angina

·

Drugs for the Heart by Lionel H. Opie, M.D. (Editor), Bernard J. Gersh (Editor), Eugene Braunwald; Paperback - 426 pages, 5th edition (January 15, 2001), W B Saunders Co; ISBN: 0721687571; http://www.amazon.com/exec/obidos/ASIN/0721687571/icongroupinterna

·

The Essential Guide to Prescription Drugs, 2001 by James J. Rybacki, James W. Long; Paperback - 1274 pages (2001), Harper Resource; ISBN: 0060958162; http://www.amazon.com/exec/obidos/ASIN/0060958162/icongroupinterna

·

Handbook of Commonly Prescribed Drugs by G. John Digregorio, Edward J. Barbieri; Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/0942447417/icongroupinterna

·

Johns Hopkins Complete Home Encyclopedia of Drugs 2nd ed. by Simeon Margolis (Ed.), Johns Hopkins; Hardcover - 835 pages (2000), Rebus; ISBN: 0929661583; http://www.amazon.com/exec/obidos/ASIN/0929661583/icongroupinterna

·

Medical Pocket Reference: Drugs 2002 by Springhouse Paperback 1st edition (2001), Lippincott Williams & Wilkins Publishers; ISBN: 1582550964; http://www.amazon.com/exec/obidos/ASIN/1582550964/icongroupinterna

·

PDR by Medical Economics Staff, Medical Economics Staff Hardcover 3506 pages 55th edition (2000), Medical Economics Company; ISBN: 1563633752; http://www.amazon.com/exec/obidos/ASIN/1563633752/icongroupinterna

·

Pharmacy Simplified: A Glossary of Terms by James Grogan; Paperback 432 pages, 1st edition (2001), Delmar Publishers; ISBN: 0766828581; http://www.amazon.com/exec/obidos/ASIN/0766828581/icongroupinterna

·

Physician Federal Desk Reference by Christine B. Fraizer; Paperback 2nd edition (2001), Medicode Inc; ISBN: 1563373971; http://www.amazon.com/exec/obidos/ASIN/1563373971/icongroupinterna

·

Physician’s Desk Reference Supplements Paperback - 300 pages, 53 edition (1999), ISBN: 1563632950; http://www.amazon.com/exec/obidos/ASIN/1563632950/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters:

Researching Your Medications 149

Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH] Amyl Nitrite: A vasodilator that is administered by inhalation. It is also used recreationally due to its supposed ability to induce euphoria and act as an aphrodisiac. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH]

Bretylium Tosylate: An agent that blocks the release of adrenergic transmitters and may have other actions. It was formerly used as an antihypertensive agent, but is now proposed as an anti-arrhythmic. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

Ephedrine: A sympathomimetic drug that stimulates thermogenesis in laboratory animals and humans. Animal studies show that it may reduce fat content and, therefore, body weight by mechanisms that probably involve increased expenditure and reduced food intake. [NIH] Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] Nadolol: A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for migraine and for tremor. [NIH]

150 Angina

Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [NIH]

Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH]

Researching Alternative Medicine 151

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to angina. Finally, at the conclusion of this chapter, we will provide a list of readings on angina from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.

What Is CAM?45 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and 45

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.

152 Angina

treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.

What Are the Domains of Alternative Medicine?46 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each. Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are

46

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

Researching Alternative Medicine 153

practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.

154 Angina

Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.

Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.

Researching Alternative Medicine 155

Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.

Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.47

47

Adapted from http://www.4woman.gov/faq/alternative.htm.

156 Angina

Is It Okay to Want Both Traditional and Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

Finding CAM References on Angina Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for angina. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required. The Combined Health Information Database For a targeted search, The Combined Health Information Database is a bibliographic database produced by health-related agencies of the Federal Government (mostly from the National Institutes of Health). This database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “angina” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique:

Researching Alternative Medicine 157

·

Addition of Acupuncture and Self-Care Education in the Treatment of Patients With Severe Angina Pectoris May Be Cost Beneficial: An Open, Prospective Study Source: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice and Policy. 5(5): 405-413. 1999. Summary: This journal article describes a cost-benefit analysis of acupuncture and self-care education added to the treatment of 75 patients with angina pectoris attending a private outpatient clinic; 75 of the patients were candidates for invasive treatment and 32 were not. The patients received acupuncture and self-care education during 12 consultations over a 4-week period. The main outcome measures were healthcare expenses, a satisfactory medical status defined as New York Heart Association (NYHA) classification 0-I and/or no use of antianginal medication, and risk of cardiac complications. For calculation of risk, three reference groups were used: published data on medical and invasive treatments, an age-matched and sex-matched control group drawn from the general Danish population, and the 211 patients in this group with angina pectoris symptoms. The estimated cost savings during 5 years of followup was $32,000 per patient, mainly due to a 90 percent reduction in hospitalization and avoidance of surgery in 52 patients (71 percent). Compared with 8 percent before treatment, 53 percent of the patients achieved a NYHA 0-I classification 1 year after treatment, and 69 percent did so after 5 years. No increased risk for myocardial infarction or cardiac death was observed. The authors conclude that acupuncture and self-care education appear to be cost-beneficial for patients with angina pectoris. The article has 3 figures, 2 tables, and 53 references.

·

Cost-Benefit of Combined Use of Acupuncture, Shiatsu and Lifestyle Adjustment for Treatment of Patients With Severe Angina Pectoris Source: Acupuncture and Electro-Therapeutics Research: The International Journal. 21(3-4): 187-195. 1996. Summary: This journal article describes a cost-benefit study of acupuncture, Shiatsu, and lifestyle adjustment for the treatment of patients with severe angina pectoris. The sample consisted of 49 patients who were candidates for coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), and 20 for whom coronary bypass surgery was rejected. Participants received a combination of 12 acupuncture treatments over 4 weeks; instruction to perform Shiatsu twice daily; and education about stress management, relaxation, exercise, and diet. They were followed for an average of 24 months, and outcomes were compared with those from a large prospective, randomized trial comparing CABG with PTCA. The

158 Angina

incidence of death and/or myocardial infarction was 21 percent among patients receiving CABG and 15 percent among those receiving PTCA, compared with 7 percent among patients in the present study. There was no difference in pain relief among the three groups. Invasive treatment was postponed in 61 percent of the patients, and the annual number of in-hospital days was reduced by 90 percent, resulting in an estimated savings of $12,000 per patient with the combined treatment. The authors conclude that the combination of acupuncture, Shiatsu, and lifestyle change may be highly cost effective for patients with advanced angina pectoris. The article has 2 figures, 3 tables, and 13 references. ·

Acupuncture in Angina Pectoris: Do Psycho-Social and Neurophysiological Factors Relate to the Effect? Source: Acupuncture and Electro-Therapeutics Research: The International Journal. 20(2): 101-116. 1995. Summary: This journal article describes a study of the effects of acupuncture in 49 patients with angina pectoris, with a focus on the relationships among those effects, psychosocial factors, and changes in skin temperature, pain thresholds, and pain tolerance. There was no significant influence on the antianginal effects of acupuncture from Minnesota Multiphasic Personality Inventory (MMPI) profiles, social stress, or patient expectations about the effects of acupuncture. Acupuncture resulted in a slight improvement in exercise tolerance, the difference in systolic blood pressure-heart rate product between rest and maximal exercise (delta PRP) and the time to onset of pain; and decreased nitroglycerine consumption and anginal attack rate. Improvement in exercise tolerance was significantly correlated with improvement in delta PRP but not to time of myocardial ischemia. Patients with a pronounced antianginal response to acupuncture had a significant increase in local skin temperature but no significant change in distant skin temperature or pain threshold compared with those who had a less pronounced response. The authors conclude that acupuncture may have a specific antianginal effect associated with hemodynamic changes but not with psychosocial factors or pain thresholds. The article has 2 figures, 4 tables, and 52 references. (AA-M).

·

Acupuncture Treatment of Angina Pectoris Based on Categorical Identification: A Clinical Report of 39 Cases Source: International Journal of Clinical Acupuncture. 6(1): 5-9. 1995. Summary: This journal article compares the outcomes of 39 patients with angina pectoris treated with acupuncture and 39 patients treated with oral isosorbide dinitrate (controls). The acupuncture group consisted of

Researching Alternative Medicine 159

17 males and 22 females with an average age of 57.6 years. Thirteen cases were complicated with hypertension, 10 with diabetes, 4 with heart failure, and 5 with arrhythmia. The control group consisted of 26 males and 13 females, average age 65.5 years. Fourteen cases were complicated with hypertension, 2 with diabetes, 1 with heart failure, and 2 with arrhythmia. The acupuncture treatment included needling at three main points plus adjunctive points appropriate to the traditional Chinese medicine diagnosis. Controls received oral isosorbide dinitrate at a dose of 10 mg three times daily. Fifteen treatments were considered a therapeutic course for both groups. There was no difference in pain relief between the groups. However, the acupuncture group had significantly greater improvement of clinical symptoms, heart rate, blood pressure, blood lipids, blood sugar, and blood flow. The authors conclude that acupuncture appears to be a beneficial, economical treatment for angina pectoris and to not have the side effects associated with drug therapy. The article has 5 tables.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov) has created a link to the National Library of Medicine’s databases to allow patients to search for articles that specifically relate to angina and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “angina” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to angina: ·

116 cases of coronary angina pectoris treated with powder composed of radix ginseng, radix notoginseng and succinum. Author(s): Yuan J, Guo W, Yang B, Liu P, Wang Q, Yuan H. Source: J Tradit Chin Med. 1997 March; 17(1): 14-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10437237&dopt=Abstract

·

A chronobiologic approach to the pharmacotherapy of hypertension and angina. Author(s): Munger MA, Kenney JK.

160 Angina

Source: The Annals of Pharmacotherapy. 2000 November; 34(11): 1313-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11098347&dopt=Abstract ·

A clinical investigation on garlicin injectio for treatment of unstable angina pectoris and its actions on plasma endothelin and blood sugar levels. Author(s): Li G, Shi Z, Jia H, Ju J, Wang X, Xia Z, Qin L, Ge C, Xu Y, Cheng L, Chen P, Yuan G. Source: J Tradit Chin Med. 2000 December; 20(4): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11263272&dopt=Abstract

·

A method for the determination of circulating aggregated platelets and its application to patients in the course of unstable angina.Author(s): Fuchs J, Joshua H, Weinberger I, Rotenberg Z, Davidson E, Agmon J. Source: Archives of Pathology & Laboratory Medicine. 1990 January; 114(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2294867&dopt=Abstract

·

A non-pharmacological approach to angina. Author(s): Orwin R. Source: Prof Nurse. 1998 June; 13(9): 583-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9782974&dopt=Abstract

·

Acupuncture for relief of angina. Author(s): Cheng TO. Source: Circulation. 1998 November 24; 98(21): 2357-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9826329&dopt=Abstract

·

Acupuncture in angina pectoris. Author(s): Kraemer ES, Cardoso Mde F, Yamamura Y. Source: Journal of Internal Medicine. 1991 April; 229(4): 383. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2026994&dopt=Abstract

Researching Alternative Medicine 161

·

Acupuncture in angina pectoris: do psycho-social and neurophysiological factors relate to the effect? Author(s): Ballegaard S, Karpatschoff B, Holck JA, Meyer CN, Trojaborg W. Source: Acupunct Electrother Res. 1995 April-July; 20(2): 101-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7491848&dopt=Abstract

·

Acupuncture in angina pectoris: does acupuncture have a specific effect? Author(s): Ballegaard S, Meyer CN, Trojaborg W. Source: Journal of Internal Medicine. 1991 April; 229(4): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2026989&dopt=Abstract

·

Acupuncture in severe, stable angina pectoris: a randomized trial. Author(s): Ballegaard S, Jensen G, Pedersen F, Nissen VH. Source: Acta Med Scand. 1986; 220(4): 307-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3541499&dopt=Abstract

·

Acupuncture treatment for angina. Author(s): Cheng TO. Source: Cardiology. 1998 October; 90(2): 152. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9778555&dopt=Abstract

·

Alternative approaches to the medical management of angina pectoris acupuncture, electrical nerve stimulation, and spinal cord stimulation. Author(s): Bueno EA, Mamtani R, Frishman WH. Source: Heart Dis. 2001 July-August; 3(4): 236-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11975800&dopt=Abstract

·

Alternative therapies for patients with persistent chronic stable angina. Author(s): Conti CR. Source: Clin Cardiol. 1999 December; 22(12): 773-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10626078&dopt=Abstract

162 Angina

·

Angina and vegan diet. Author(s): Ellis FR, Sanders TA. Source: American Heart Journal. 1977 June; 93(6): 803-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=860681&dopt=Abstract

·

Angina pectoris and therapy with cisplatin, vincristine, and bleomycin. Author(s): Dixon A, Nakamura JM, Oishi N, Wachi DH, Fukuyama O. Source: Annals of Internal Medicine. 1989 August 15; 111(4): 342-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2474263&dopt=Abstract

·

Angina pectoris associated with infusions of 5-FU and vindesine. Author(s): Blijham GH, Fiolet HH, van Deijk WA, Hupperets PS, Janssen JH. Source: Cancer Treat Rep. 1986 February; 70(2): 314-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3948198&dopt=Abstract

·

Angina pectoris following cisplatin, etoposide, and bleomycin in a patient with advanced testicular cancer. Author(s): Rodriguez J, Collazos J, Gallardo M, Hernando G. Source: The Annals of Pharmacotherapy. 1995 February; 29(2): 138-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7538830&dopt=Abstract

·

Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment? Author(s): Hautvast RW, DeJongste MJ, ter Horst GJ, Blanksma PK, Lie KI. Source: Clin Cardiol. 1996 July; 19(7): 531-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8818432&dopt=Abstract

·

Antianginal and cardiopretective effects of terminalia arjuna.Author(s): Anand V.

Researching Alternative Medicine 163

Source: J Assoc Physicians India. 1994 September; 42(9): 757. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7883693&dopt=Abstract ·

Antianginal and cardiopretective effects of terminalia arjuna. Author(s): Chopra B. Source: J Assoc Physicians India. 1994 September; 42(9): 756. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7883690&dopt=Abstract

·

Antianginal and cardioprotective effects of Terminalia arjuna, an indigenous drug, in coronary artery disease. Author(s): Dwivedi S, Agarwal MP. Source: J Assoc Physicians India. 1994 April; 42(4): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7741874&dopt=Abstract

·

Antithrombin III and protein C in stable angina pectoris--influence of dietary supplementation with polyunsaturated fatty acids. Author(s): Schmidt EB, Kristensen SD, Sorensen PJ, Dyerberg J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1988 September; 48(5): 469-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3060987&dopt=Abstract

·

Bedside implantation of a trial spinal cord stimulator for intractable anginal pain. Author(s): Janfaza DR, Michna E, Pisini JV, Ross EL. Source: Anesthesia and Analgesia. 1998 December; 87(6): 1242-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9842805&dopt=Abstract

·

Behavioral treatment of angina-like chest pain in patients with hyperventilation syndrome. Author(s): Hegel MT, Abel GG, Etscheidt M, Cohen-Cole S, Wilmer CI.

164 Angina

Source: Journal of Behavior Therapy and Experimental Psychiatry. 1989 March; 20(1): 31-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2671050&dopt=Abstract ·

Beneficial effect of Inula racemosa (pushkarmoola) in angina pectoris: a preliminary report. Author(s): Tripathi SN, Upadhyaya BN, Gupta VK. Source: Indian J Physiol Pharmacol. 1984 January-March; 28(1): 73-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6436179&dopt=Abstract

·

Catecholamine metabolism during pacing-induced angina pectoris and the effect of transcutaneous electrical nerve stimulation. Author(s): Emanuelsson H, Mannheimer C, Waagstein F, Wilhelmsson C. Source: American Heart Journal. 1987 December; 114(6): 1360-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3500628&dopt=Abstract

·

Clinical characteristics of patients with variant angina complicated by myocardial infarction or death within 1 month. Author(s): Waters DD, Szlachcic J, Miller D, Theroux P. Source: The American Journal of Cardiology. 1982 March; 49(4): 658-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7064815&dopt=Abstract

·

Clinical observation on 300 cases of angina pectoris treated by the spleen-stomach regulating method. Author(s): Gao R, Li L, Lu Z. Source: J Tradit Chin Med. 1998 June; 18(2): 87-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10437220&dopt=Abstract

·

Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris. Author(s): Kinoshita M, Nishikawa S, Sawamura M, Yamaguchi S, Mitsunami K, Itoh M, Motomura M, Bito K, Mashiro I, Kawakita S. Source: The American Journal of Cardiology. 1986 October 1; 58(9): 733-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2945420&dopt=Abstract

Researching Alternative Medicine 165

·

Comparison of combination nifedipine-propranolol and diltiazempropranolol with high dose diltiazem monotherapy for stable angina pectoris. Author(s): Morse JR. Source: The American Journal of Cardiology. 1988 November 15; 62(16): 1028-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3055924&dopt=Abstract

·

Comparison of oral propranolol and verapamil for combined systemic hypertension and angina pectoris. A placebo-controlled double-blind randomized crossover trial. Author(s): Frishman WH, Klein NA, Klein P, Strom JA, Tawil R, Strair R, Wong B, Roth S, LeJemtel TH, Pollack S, Sonnenblick EH. Source: The American Journal of Cardiology. 1982 November; 50(5): 116472. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=6127946&dopt=Abstract

·

Cooling down unstable angina with high dosage of isosorbide dinitrate (ISDN) continuously infused. Author(s): Distante A, Sabino F, L'Abbate A. Source: European Heart Journal. 1988 January; 9 Suppl A: 155-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3409912&dopt=Abstract

·

Coronary blood flow dynamics during transcutaneous electrical nerve stimulation for stable angina pectoris associated with severe narrowing of one major coronary artery. Author(s): Jessurun GA, Tio RA, De Jongste MJ, Hautvast RW, Den Heijer P, Crijns HJ. Source: The American Journal of Cardiology. 1998 October 15; 82(8): 9216. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9794345&dopt=Abstract

·

DATA: a decision aid for management of the patient with stable angina pectoris. Author(s): Hopkins CB, Maysuria H.

166 Angina

Source: Crit Rev Biomed Eng. 2000; 28(1-2): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10999363&dopt=Abstract ·

Effect of acupuncture in patients with angina pectoris. Author(s): Richter A, Herlitz J, Hjalmarson A. Source: European Heart Journal. 1991 February; 12(2): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2044550&dopt=Abstract

·

Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary arteriograms. Author(s): Egashira K, Hirooka Y, Kuga T, Mohri M, Takeshita A. Source: Circulation. 1996 July 15; 94(2): 130-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8674170&dopt=Abstract

·

Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. Author(s): Bednarz B, Wolk R, Chamiec T, Herbaczynska-Cedro K, Winek D, Ceremuzynski L. Source: International Journal of Cardiology. 2000 September 15; 75(2-3): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11077135&dopt=Abstract

·

Electrical neurostimulation for angina pectoris. Acupuncture and TENS--where east meets west. Author(s): Colquhoun DM. Source: Med J Aust. 1993 April 5; 158(7): 440-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8469188&dopt=Abstract

·

Epidural spinal electrical stimulation for severe angina: a study of its effects on symptoms, exercise tolerance and degree of ischaemia. Author(s): Sanderson JE, Brooksby P, Waterhouse D, Palmer RB, Neubauer K. Source: European Heart Journal. 1992 May; 13(5): 628-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1618204&dopt=Abstract

Researching Alternative Medicine 167

·

Failure of adjuvant heparin to reduce myocardial ischemia in the early treatment of patients with unstable angina. Author(s): Wallis DE, Boden WE, Califf R, Crawford MH, Hakki AH, Iskandrian AS, Labovitz A, O'Connor C, Sutton R, Scanlon PJ. Source: American Heart Journal. 1991 October; 122(4 Pt 1): 949-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1681722&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

·

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

·

Chinese Medicine: http://www.newcenturynutrition.com/

·

drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

·

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

·

Google: http://directory.google.com/Top/Health/Alternative/

·

Open Directory Project: http://dmoz.org/Health/Alternative/

·

TPN.com: http://www.tnp.com/

·

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

·

WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

·

WellNet: http://www.wellnet.ca/herbsa-c.htm

The following is a specific Web list relating to angina; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

General Overview Angina Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm

168 Angina

Angina Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsLookups/Uses/an gina.html Angina Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html ·

Alternative Therapy Acupuncture Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Therapy/Acupuncture.htm Chelation therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679, 00.html

·

Chinese Medicine Bawei Chenxiang San Alternative names: Bawei Chenxiang Powder Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Bawei%20Chenxia ng%20San&mh=10&sb=---&view_records=View+Records Danshen Alternative names: Danshen Root; Radix Salviae Miltiorrhizae Source: Chinese Materia Medica Hyperlink: http://www.newcenturynutrition.com/ Fufang Danshen Pian

Researching Alternative Medicine 169

Alternative names: Compound Saivia Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Fufang%20Danshe n%20Pian&mh=10&sb=---&view_records=View+Records Gualou Alternative names: Snakegourd Fruit; Fructus Trichosanthis Source: Chinese Materia Medica Hyperlink: http://www.newcenturynutrition.com/ Guanxin Suhe Alternative names: Guanxin Suhe Pills; Guanxin Suhe Wan Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Guanxin%20Suhe& mh=10&sb=---&view_records=View+Records Jiangxiang Alternative names: Rosewood; Lignum Dalbergiae Odoriferae Source: Chinese Materia Medica Hyperlink: http://www.newcenturynutrition.com/ Jingzhi Guanxin Pian Alternative names: Jingzhi Guanxin Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Jingzhi%20Guanxi n%20Pian&mh=10&sb=---&view_records=View+Records Lingbao Huxin Dan Alternative names: Lingbao Huxin Micropills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Lingbao%20Huxin %20Dan&mh=10&sb=---&view_records=View+Records Shexiang Baoxin Wan

170 Angina

Alternative names: Shexiang Baoxin Pills; Shexiang Baoxin Wan
(She Xiang Bao Xin Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Shexiang%20Baoxi n%20Wan&mh=10&sb=---&view_records=View+Records Shuxin Koufuye Alternative names: Shuxin Oral Liquid; Shuxin Koufuye
(Shu Xin Kou Fu Ye) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Shuxin%20Koufuye &mh=10&sb=---&view_records=View+Records Shuxiong Pian Alternative names: Shuxiong Tablets; Shuxiong Pian
(Shu Xiong Pi An) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Shuxiong%20Pian &mh=10&sb=---&view_records=View+Records Tanxiang Alternative names: Sandalwood; Lignum Santaii Albi Source: Chinese Materia Medica Hyperlink: http://www.newcenturynutrition.com/ Xiebai Alternative names: Longstamen Onion Bulb; Xiebai (Xie Bai); Bulbus Aiiii Macrostemi Source: Chinese Materia Medica Hyperlink: http://www.newcenturynutrition.com/ ·

Herbs and Supplements Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/

Researching Alternative Medicine 171

Alpha2-Adrenergic Agonists Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Cardio vascularMedicationsAlpha2AdrenergicAgonistscl.html Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Amino_Acids.htm Amlodipine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Amlodipine.htm Ananas comosus Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Brom elaincs.html Arginine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Arginine.htm Arginine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Arginine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 05,00.html Arnica Alternative names: Arnica montana Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Arnicach.html

172 Angina

Arnica montana Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Arnicach.html Astragalus mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Atenolol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Atenolol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Atenolol.htm Beta-Adrenergic Blockers Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Beta_Blockers.htm Beta-Blockers Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Beta-Blockers Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Cardio vascularMedicationsBetaBlockerscl.html Beta-Carotene Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000104.html Betaine Source: Integrative Medicine Communications; www.onemedicine.com

Researching Alternative Medicine 173

Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Bromelain Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Bromelain Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Bromelain.htm Bromelain Alternative names: Ananas comosus, Bromelainum Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Brom elaincs.html Bromelainum Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Brom elaincs.html Coenzyme Q Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,768, 00.html Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Coenzyme_Q10.htm

174 Angina

Coenzyme Q10 Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000135.html Colestipol Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Coleus forskohlii Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000136.html Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Crataegus laevigata Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Hawthornc h.html Crataegus monogyna Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Hawthornc h.html Cysteine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Cyst einecs.html

Researching Alternative Medicine 175

Cysteine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/InteractiveMedicine/ConsSupplements/Inter actions/Cysteinecs.html Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/DHEA.htm Diltiazem Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Diltiazem.htm Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/DHA.htm Fiber Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Fibric Acid Derivatives Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Cholest erolLoweringMedicationsFibricAcidDerivativescl.html Fo-Ti Alternative names: Polygonum multiflorum Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Fo-ti.htm Gemfibrozil Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Ginger

176 Angina

Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Ginger Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Ginkgo Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Ginkgo Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Glutamic Acid Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Glutamic_Acid.htm Hawthorn Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Hawthorn Alternative names: Crataegus laevigata, Crataegus oxyacantha, Crataegus monogyna Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Hawthorn.htm Hawthorn Source: Integrative Medicine Communications; www.onemedicine.com

Researching Alternative Medicine 177

Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Hawthornc h.html Hawthorn Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Hawthorn Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000178.html Hawthorn Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hyperlink: http://www.wellnet.ca/herbsg-i.htm Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 35,00.html Heparin Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Herbal Medicine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html

178 Angina

Indian Tobacco Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Isosorbide Dinitrate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Isosorbide_Dinitrate.htm Isosorbide Mononitrate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Isosorbide_Mononitrate. htm Kudzu Alternative names: Pueraria lobata Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Kudzu.htm L-Arginine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Linden Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Lipoic Acid Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Metoprolol Source: Healthnotes, Inc.; www.healthnotes.com

Researching Alternative Medicine 179

Hyperlink: http://www.thedacare.org/healthnotes/Drug/Metoprolol.htm Mistletoe Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Motherwort Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html N-Acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/N_Acetyl_Cysteine.htm N-Acetyl Cysteine (NAC) Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000211.html N-acetylcysteine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Nadolol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Nadolol.htm Nifedipine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Nifedipine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Nifedipine.htm

180 Angina

Nitro-Bid Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Nitro-Dur Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Nitroglycerin Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Nitroglycerin.htm Nitroglycerin Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Nitroglycerin Alternative names: Deponit, Minitran, Nitrek, Nitro-Bid, Nitro-Derm, Nitro-Dur, Nitro-Time, Nitrocine, Nitrodisc, Nitrogard, Nitroglyn, Nitrol, Nitrolingual, Nitrong, NitroQuick, Nitrostat, Transderm-Nitro Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000363.html Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Phenothiazine Derivatives Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Psycho therapeuticMedicationsPhenothiazineDerivativescl.html Propranolol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm

Researching Alternative Medicine 181

Propranolol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Propranolol.htm Royal Jelly Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Royal_Jelly.htm Spleen Extracts Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Spleen_Extracts.htm Sulfonylureas Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Antidia beticMedicationsSulfonylureascl.html Taurine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 59,00.html Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Thiazide Diuretics Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Diureti csThiazideDiureticscl.html Thioxanthene Derivatives Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Psycho therapeuticMedicationsThioxantheneDerivativescl.html

182 Angina

Transderm-Nitro Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Tricyclic Antidepressants (TCAs) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Antide pressantMedicationsTCAscl.html Vasodilators Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Cardio vascularMedicationsVasodilatorscl.html Verapamil Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Verapamil.htm ·

Related Conditions Alzheimer's Disease, Non-Alzheimer's Dementia, and Normal AgeRelated Memory Loss Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000259.html Arteries, Hardening of Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Arteriosclerosis Source: Integrative Medicine Communications; www.onemedicine.com

Researching Alternative Medicine 183

Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Atherosclerosis.htm Atherosclerosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000263.html Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cardiomyopathy.htm Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cardiovascular_Dise ase.htm Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Congestive_Heart.htm Congestive Heart Failure Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000283.html Coronary Artery Disease Source: Integrative Medicine Communications; www.onemedicine.com

184 Angina

Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Gastroesophageal Reflux Disease Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Gastro esophagealRefluxDiseasecc.html Headache, Migraine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Heada cheMigrainecc.html Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Heart_Attack.htm Heartburn Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Gastro esophagealRefluxDiseasecc.html Migraine Headache Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Heada cheMigrainecc.html Stroke Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Stroke.htm

Researching Alternative Medicine 185

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Alternative Medicine for Dummies by James Dillard (Author); Audio Cassette, Abridged edition (1998), Harper Audio; ISBN: 0694520659; http://www.amazon.com/exec/obidos/ASIN/0694520659/icongroupinterna ·

Complementary and Alternative Medicine Secrets by W. Kohatsu (Editor); Hardcover (2001), Hanley & Belfus; ISBN: 1560534400; http://www.amazon.com/exec/obidos/ASIN/1560534400/icongroupinterna

·

Dictionary of Alternative Medicine by J. C. Segen; Paperback-2nd edition (2001), Appleton & Lange; ISBN: 0838516211; http://www.amazon.com/exec/obidos/ASIN/0838516211/icongroupinterna

·

Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating by Walter C. Willett, MD, et al; Hardcover - 352 pages (2001), Simon & Schuster; ISBN: 0684863375; http://www.amazon.com/exec/obidos/ASIN/0684863375/icongroupinterna

· Encyclopedia of Natural Medicine, Revised 2nd Edition by Michael T. Murray, Joseph E. Pizzorno; Paperback - 960 pages, 2nd Rev edition (1997), Prima Publishing; ISBN: 0761511571; http://www.amazon.com/exec/obidos/ASIN/0761511571/icongroupinterna ·

Integrative Medicine: An Introduction to the Art & Science of Healing by Andrew Weil (Author); Audio Cassette, Unabridged edition (2001), Sounds True; ISBN: 1564558541; http://www.amazon.com/exec/obidos/ASIN/1564558541/icongroupinterna

· Textbook of Complementary and Alternative Medicine by Wayne B. Jonas; Hardcover (2003), Lippincott, Williams & Wilkins; ISBN: 0683044370; http://www.amazon.com/exec/obidos/ASIN/0683044370/icongroupinterna · A Textbook on Edta Chelation Therapy by Elmer M. Cranton (Editor), Linus Pauling; Hardcover - 563 pages, 2nd edition (April 2001), Hampton

186 Angina

Roads Pub Co; ISBN: 1571742530; http://www.amazon.com/exec/obidos/ASIN/1571742530/icongroupinterna For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Researching Nutrition 187

APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients with angina. Any dietary recommendation is based on a patient’s age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with angina may be given different recommendations. Some recommendations may be directly related to angina, while others may be more related to the patient’s general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of angina. We will then show you how to find studies dedicated specifically to nutrition and angina.

188 Angina

Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·

Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.

·

Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

·

Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.

·

Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.

Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·

Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.

·

Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.

·

Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from

Researching Nutrition 189

nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·

Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains

·

Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.

·

Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.

·

Vitamin C allows the body’s immune system to fight various diseases, strengthens body tissue, and improves the body’s use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.

·

Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.

·

Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.

·

Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.

·

Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.

It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·

Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.

·

Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.

190 Angina

·

Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.

·

Iodine helps regulate the body’s use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.

·

Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.

·

Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.

·

Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.

·

Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.

·

Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.

The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation based on your specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:48 ·

DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.

·

DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.

48

Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.

Researching Nutrition 191

·

RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”

·

RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?49

Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”50 According to the ODS, dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.51 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where the use of plant products, in particular, has a long tradition. However, the This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 50 Contact: The Office of Dietary Supplements, National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: (301) 435-2920, Fax: (301) 480-1845, E-mail: [email protected]. 51 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 49

192 Angina

overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of Dietary Supplements National Institutes of Health Building 31, Room 1B29 31 Center Drive, MSC 2086 Bethesda, Maryland 20892-2086 Tel: (301) 435-2920 Fax: (301) 480-1845 E-mail: [email protected]

Finding Studies on Angina The NIH maintains an office dedicated to patient nutrition and diet. The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.52 IBIDS is available to the public free of charge through the ODS Internet page: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back periodically as this database is frequently updated. More studies can be Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

52

Researching Nutrition 193

found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “angina” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following is a typical result when searching for recently indexed consumer information on angina: ·

Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Author(s): Centro Diabetico Ospedale di Marino, Italy. Source: Tatti, P Pahor, M Byington, R P Di Mauro, P Guarisco, R Strollo, G Strollo, F Diabetes-Care. 1998 April; 21(4): 597-603 0149-5992

The following information is typical of that found when using the “Full IBIDS Database” when searching using “angina” (or a synonym): ·

Acupuncture treatment of angina pectoris. Author(s): First People's Hospital of Yuhang City, Zhejiang Province. Source: Li, Y J-Tradit-Chin-Med. 1999 December; 19(4): 279-82 0254-6272

·

An uncommon case of variant angina. Author(s): Divisione di Cardiologia, IRCCS H San Raffaele, Milano. Source: Stazi, F Meloni, C Ballarotto, C G-Ital-Cardiol. 1999 October; 29(10): 1208-11 0046-5968

·

Anticoagulant therapy in unstable angina. Author(s): Department of Medicine, University of Alberta, Edmonton, Canada. Source: Choy, J B Armstrong, P W Cardiol-Clin. 1999 May; 17(2): 327-43, ix 0733-8651

·

ATP dependent K+ channel: a novel therapeutic target in unstable angina. Source: Dana, A Yellon, D M Eur-Heart-J. 1999 January; 20(1): 2-5 0195668X

·

Dissociation of platelet activation and spontaneous myocardial ischemia in unstable angina. Author(s): Cardiovascular Research Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom. Source: Vejar, M Fragasso, G Hackett, D Lipkin, D P Maseri, A Born, G V Ciabattoni, G Patrono, C Thromb-Haemost. 1990 April 12; 63(2): 163-8 0340-6245

194 Angina

·

Effect of L-arginine administration on myocardial thallium-201 perfusion during exercise in patients with angina pectoris and normal coronary angiograms. Author(s): First Department of Internal Medicine, Kobe University School of Medicine, Japan. [email protected] Source: Fujita, H Yamabe, H Yokoyama, M J-Nucl-Cardiol. 2000 MarApril; 7(2): 97-102 1071-3581

·

Evaluating risk in unstable angina: role of pharmacological stress echocardiography. Source: Pierard, L A Eur-Heart-J. 2000 July; 21(13): 1041-3 0195-668X

·

Feasibility and prognostic value of dobutamine-atropine stress echocardiography early in unstable angina. Author(s): Cardiovascular Institute, University of Barcelona, Spain. Source: Sitges, M Pare, C Azqueta, M Bosch, X Miranda Guardiola, F Velamazan, M Magrina, J Sanz, G Eur-Heart-J. 2000 July; 21(13): 1063-71 0195-668X

·

Limited efficacy of magnesium for the treatment of variant angina. Author(s): Department of Cardiology, Saiseikai Saijo Hospital, Ehime. Source: Sueda, S Saeki, H Otani, T Mineoi, K Kondo, T Yano, K Ochi, T Ochi, N Kawada, H Matsuda, S Hayashi, Y Tsuruoka, T Uraoka, T JCardiol. 1999 September; 34(3): 139-47 0914-5087

·

Long-term home treatment with epidural analgesia does not affect later spinal cord stimulation in patients with otherwise intractable angina pectoris. Author(s): Department of Cardiothoracic Anaesthesia, Odense University Hospital, Denmark. Source: Andersen, C Hole, P Clin-J-Pain. 1998 December; 14(4): 315-9 0749-8047

·

Mesenteric angina complicating a mesodermal anomaly. Author(s): Department of Paediatric Neurology, Royal Hospital for Sick Children, St Michael's Hill, Bristol, England. [email protected] Source: Howells, R Curran, A Jardine, P Newbury Ecob, R Sandhu, B Europ-J-Paediatr-Neurol. 2000; 4(4): 181-3 1090-3798

·

New combined spasm provocation test in patients with rest angina: intracoronary injection of acetylcholine after intracoronary administration of ergonovine. Author(s): Takanoko Hospital, Matsuyama City, Japan. Source: Sueda, S Ochi, T Yano, K Mineoi, K Kondou, T Ochi, N Hayashi, Y Kukita, H Matsuda, S Kawada, H Tsuruoka, T Uraoka, T Jpn-Circ-J. 2000 August; 64(8): 559-65 0047-1828

Researching Nutrition 195

·

Plasma selenium and glutathione peroxidase in relation to cancer, angina pectoris and short-term mortality in 68-year-old men. Author(s): Department of Clinical Chemistry, University Hospital, Lund, Sweden. Source: Akesson, B Steen, B Compr-Gerontol-[A]. 1987 June; 1(2): 61-4 0902-0071

·

Platelet activation during provocation of coronary artery spasm by ergonovine and cold pressor testing in patients with angina pectoris. Author(s): Cardiology Institute, St Petersburg, Russia. Source: Gurevich, V S Mikhailova, I A Kuleshova, E V Tsibina, T G Blood-Coagul-Fibrinolysis. 1996 March; 7(2): 181-2 0957-5235

·

Preserved endothelial function in the spastic segment of the human epicardial coronary artery in patients with variant angina--role of substance P in evaluating endothelial function. Author(s): Department of Medicine, Kyushu Welfare Pension Hospital, Japan. Source: Yamamoto, H Eur-Heart-J. 1993 November; 14 Suppl I118-22 0195-668X

·

Proposal for clinical trials using anti-inflammatory drugs in the therapy of angina pectoris, myocardial infarction and coronary restenosis after angioplasty and bypass grafting. Author(s): Laboratory of Electron Microscopy, Varna Institute of Medicine, Bulgaria. Source: Chaldakov, G N Med-Hypotheses. 1992 February; 37(2): 74-5 0306-9877

·

Relationship between the coronary diameter and occurrence of vasospastic angina in patients with normal coronary arteries. Author(s): 2nd Department of Internal Medicine, Kansai Medical University, Oska, Japan. Source: Kurimoto, T Karakawa, M Baden, M Matsuura, T Shimada, T Sugiura, T Inada, M Jpn-Circ-J. 1989 July; 53(7): 747-55 0047-1828

·

Super-aspirins in severe angina. Source: Anonymous Harv-Heart-Lett. 1998 December; 9(4): 1-3 1051-5313

·

TCM differential treatment of angina pectoris--an illustrative case report. Author(s): Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing. Source: Zhang, D Yu, Y Tu, X J-Tradit-Chin-Med. 1999 September; 19(3): 234-7 0254-6272

196 Angina

·

Temporal variability and correlation with geometric parameters in vasospastic angina: a quantitative angiographic study. Author(s): Department of Interventional Cardiology, Erasmus University, Rotterdam, The Netherlands. Source: Ozaki, Y Keane, D Haase, J Baptista, J Meneveau, N de Feyter, P J Takatsu, F Serruys, P W Eur-Heart-J. 1994 January; 15(1): 61-7 0195-668X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

·

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

·

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

·

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

·

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

·

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

·

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

·

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Researching Nutrition 197

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

·

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

·

Google: http://directory.google.com/Top/Health/Nutrition/

·

Healthnotes: http://www.thedacare.org/healthnotes/

·

Open Directory Project: http://dmoz.org/Health/Nutrition/

·

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

·

WebMDÒHealth: http://my.webmd.com/nutrition

·

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

The following is a specific Web list relating to angina; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

Vitamins Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904, 00.html Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Vitamin_E.htm Vitamin E Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000092.html Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

198 Angina

Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906, 00.html ·

Minerals Alpha-Tocopherol Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Calcium-Channel Blockers Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Calcium_Channel_Block ers.htm Carnitine Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000088.html Carnitine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 12,00.html Carnitine (L-Carnitine) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Carn itineLCarnitinecs.html HMG-CoA Reductase Inhibitors (Statins) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsDepletions/Cholest erolLoweringMedicationsHMGCoAReductaseInhibitorscl.html L-Carnitine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm

Researching Nutrition 199

L-Carnitine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Carnitine.htm L-Carnitine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/Carn itineLCarnitinecs.html Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Magnesium.htm Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Magnesium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Magnesium Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000202.html Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890, 00.html Potassium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 86,00.html

200 Angina

Selenium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Statins Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html ·

Food and Diet Coffee Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Food_Guide/Coffee.htm Coffee Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Diabetes Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Fats Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html

Researching Nutrition 201

Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Fish Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Fish Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Fruit Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Garlic Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Grains Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html High Cholesterol Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Magnesium Sulfate Source: Healthnotes, Inc.; www.healthnotes.com

202 Angina

Hyperlink: http://www.thedacare.org/healthnotes/Concern/Angina.htm Monounsaturated Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Nuts Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Obesity Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Onions Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Saturated Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Saturated Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Sugar Source: Integrative Medicine Communications; www.onemedicine.com

Researching Nutrition 203

Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Tea Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html The Dean Ornish Diet Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Diet/Dean_Ornish_Diet.htm Vegetables Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Vegetables Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html Water Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Angina cc.html Water Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Athero sclerosiscc.html

204 Angina

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Carbohydrates: A nutrient that supplies 4 calories/gram. They may be simple or complex. Simple carbohydrates are called sugars, and complex carbohydrates are called starch and fiber (cellulose). An organic compound—containing carbon, hydrogen, and oxygen—that is formed by photosynthesis in plants. Carbohydrates are heat producing and are classified as monosaccharides, disaccharides, or polysaccharides. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that

Researching Nutrition 205

is converted to its active metabolite fosinoprilat. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH]

Physical Activity and Cardiovascular Health 207

APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.53

53

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

208 Angina

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):54 ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM

·

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

·

California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html

·

California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html

·

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/

54

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Physical Activity and Cardiovascular Health 209

·

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

·

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

·

California: San José PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

·

California: University of California, Davis. Health Sciences Libraries

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

·

California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

·

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

·

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

·

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/

210 Angina

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm

·

Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

Physical Activity and Cardiovascular Health 211

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

·

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

212 Angina

·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) - provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

·

Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld

·

New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/

·

New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

·

New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html

·

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

·

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

·

Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

Physical Activity and Cardiovascular Health 213

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html

·

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

·

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

·

South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters:

214 Angina

Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Coagulation: 1. the process of clot formation. 2. in colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. in surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH] Hypertriglyceridemia: An excess of triglycerides in the blood that is an autosomal dominant disorder with the phenotype of hyperlipoproteinemia, type IV. The National Cholesterol Education Program defines a high level of triglycerides as being between 400 and 1,000 mg/dL. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or

Physical Activity and Cardiovascular Health 215

operative injury), vasculitis, or uraemia. [EU] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Sedentary: 1. sitting habitually; of inactive habits. 2. pertaining to a sitting posture. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] VLDL: Very low-density lipoprotein. The lipoprotein particles that initially leave the liver, carrying cholesterol and lipid. VLDLs contain 10 to 15 percent of the total serum cholesterol along with most of the triglycerides in the fasting serum; VLDLs are precursors of LDL, and some forms of VLDL, particularly VLDL remnants, appear to be atherogenic. [NIH]

216 Angina

Physical Activity and Cardiovascular Health 217

APPENDIX E. TRIGLYCERIDE, HIGH DENSITY LIPOPROTEIN, AND CORONARY HEART DISEASE Overview NIH Consensus Development Conferences are convened to evaluate available scientific information and resolve safety and efficacy issues related to biomedical technology. The resultant NIH Consensus Statements are intended to advance understanding of the technology or issue in question and to be useful to health professionals and the public.55 Each NIH consensus statement is the product of an independent, non-Federal panel of experts and is based on the panel’s assessment of medical knowledge available at the time the statement was written. Therefore, a consensus statement provides a “snapshot in time” of the state of knowledge of the conference topic. The NIH makes the following caveat: “When reading or downloading NIH consensus statements, keep in mind that new knowledge is inevitably accumulating through medical research. Nevertheless, each NIH consensus statement is retained on this website in its original form as a record of the NIH Consensus Development Program.”56 The following concensus statement was posted on the NIH site and not indicated as “out of date” in March 2002. It was originally published, however, in February, 1992.57

This paragraph has been adapted from the NIH: http://odp.od.nih.gov/consensus/cons/cons.htm. 56 Adapted from the NIH: http://odp.od.nih.gov/consensus/cons/consdate.htm. 57 Triglyceride, High Density Lipoprotein, and Coronary Heart Disease. NIH Consensus Statement Online 1992 Feb 26-28 [cited 2002 February 15];10(2):1-28. http://consensus.nih.gov/cons/089/089_statement.htm 55

218 Angina

Abstract The National Institutes of Health Consensus Development Conference on Triglyceride, High Density Lipoprotein, and Coronary Heart Disease brought together experts in lipid metabolism, epidemiologists, and clinicians as well as other health care professionals and the public to address the following questions: (1) Is the relationship of high triglyceride and/or low HDL cholesterol with coronary heart disease causal? (2) Will reduction of high triglyceride and/or elevation of HDL cholesterol help prevent coronary heart disease? (3) Under what circumstances should triglycerides and HDL cholesterol be measured? (4) Under what circumstances should active intervention to lower triglyceride and/or raise HDL cholesterol be considered in high risk individuals and the general population? (5) What can be accomplished by dietary, other hygienic, and drug treatments? (6) What are the significant questions for future research? Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel concluded that (1) existing data provide considerable support for a causal relationship between low HDL and CHD; however, with respect to TG, data are mixed and the evidence on a causal relationship is incomplete; (2) initial TG and/or HDL levels modify benefit achieved by lowering low density lipoprotein cholesterol (LDL-C); however, evidence from clinical trials is insufficient to draw conclusions about specific benefits of TG- and/or HDL-altering therapy; (3) HDL-C measurement should be added to total cholesterol measurement when evaluating CHD risk in healthy individuals provided accuracy of measurement, appropriate counseling, and followup can be assured; (4) there is general agreement with the Adult Treatment Panel (ATP) guidelines that LDL-C is essential in cardiovascular risk assessment, as well as that persons with elevations of LDL-C greater than 150 mg/dL refractory to nondrug therapies may require drug treatment; (5) there is strong consensus that hygienic approaches (diet, exercise, smoking cessation, weight loss) should be employed to lower TG and/or raise HDL; there is no consensus for the use of drug treatment in patients with borderline hypertriglyceridemia and low HDL-C levels in the presence of a desirable LDL-C level. The full text of the consensus panel’s statement follows.

Physical Activity and Cardiovascular Health 219

What Is Triglyceride, High Density Lipoprotein? Great progress has been made over the past 30 years in identifying cardiovascular risk factors and in developing and implementing measures to correct them. The guidelines developed by the Adult Treatment Panel (ATP) of the National Cholesterol Education Program identified low density lipoprotein (LDL) as the major atherogenic lipoprotein and high levels of LDL cholesterol as the primary target for cholesterol-lowering therapy. The ATP recognized low HDL cholesterol (< 35 mg/dL) as a major risk factor for coronary heart disease (CHD). It recommended that HDL cholesterol be measured in all patients with high blood cholesterol (greater than or equal to 240 mg/dL) and in those patients with borderline high blood cholesterol (200-239 mg/dL) who had definite CHD or two other CHD risk factors (one of which could be male sex). Low HDL cholesterol was entered in the treatment decision algorithm as one of the major risk factors that would affect the assessment of overall coronary risk and therefore influence clinical decisions about treatment. The ATP report listed major causes of reduced serum HDL cholesterol, and although there had been no clinical trials demonstrating the benefit of raising HDL cholesterol, the ATP made recommendations to raise HDL concentrations by hygienic means. The report noted the possible benefit of raising HDL concomitant with reducing elevated LDL; however, drug therapy was not advocated specifically to raise HDL cholesterol in patients without high LDL cholesterol levels. The ATP also addressed hypertriglyceridemia using definitions and recommendations of the National Institutes of Health Consensus Development Conference on Treatment of Hypertriglyceridemia, which convened in September 1983. The ATP regarded the relationship between plasma triglyceride levels and cardiovascular disease as controversial. The report stated that consistent evidence is lacking to support recognition of triglyceride as an independent risk factor of CHD. Instead, the ATP suggested that plasma triglyceride levels probably reflected the presence of certain atherogenic proteins and might be a clue to the presence of other lipoprotein abnormalities that were more directly associated with CHD, such as low HDL cholesterol, low apoprotein A-1, or elevated apoprotein B. It was noted that hypertriglyceridemia alone might be a marker for familial combined hyperlipidemia. The ATP further recognized that many disease entities that elevate triglyceride levels, such as diabetes mellitus, nephrotic syndrome, and chronic renal disease, carry an increased risk of CHD. Other secondary causes of hypertriglyceridemia, such as commonly used drugs, also were listed. Hygienic measures were recommended for all individuals with hypertriglyceridemia; however, drug therapy was advocated only for

220 Angina

those with marked hypertriglyceridemia who did not respond adequately to modification of diet. The ATP recommended that the triglyceride levels be measured in all patients with high blood cholesterol and in those patients with borderline high blood cholesterol who had definite CHD or two other CHD risk factors. Since these guidelines were developed, the scientific data base has significantly expanded. Genetic investigations into familial dyslipidemias, advances in molecular biology, animal experiments, human observational studies, lipid metabolic studies, epidemiologic data, and the results of interventional clinical trials looking at mortality, cardiovascular endpoints, and angiographic changes in atheromatous lesions have created interest in further examination of the role of HDL cholesterol and triglycerides in the pathogenesis of coronary artery disease. The consensus conference was designed to address the following questions: ·

Is the relationship of high triglyceride and/or low HDL levels with coronary heart disease causal?

·

Will reduction of high triglyceride and/or elevation of HDL cholesterol help prevent coronary heart disease?

·

Under what circumstances should triglycerides and HDL be measured?

·

What can be accomplished by dietary, drug, and other hygienic treatments?

·

Under what circumstances should active intervention to lower triglyceride and/or raise HDL cholesterol be considered in high-risk individuals and the general population?

·

What are the significant questions for continuing research?

To address these questions, the National Heart, Lung, and Blood Institute and the Office of Medical Applications of Research of the National Institutes of Health convened a Consensus Development Conference on Triglyceride, High Density Lipoprotein, and Coronary Heart Disease on February 26-28, 1992. After 2 days of presentations by experts and discussion by the audience, a consensus panel drawn from specialists and generalists from the medical profession and related scientific disciplines, clinical investigators, and public representatives considered the evidence and came to the following conclusions.

Physical Activity and Cardiovascular Health 221

Causal Relationship: Triglyceride, HDL, and Coronary Heart Disease Associations between triglyceride, HDL, and coronary heart disease are well described in the literature. Causality may be inferred based on consistency of the data, strength of association, temporality, dose response, specificity, and biologic plausibility. The relevant observations for these criteria are described below. HDL A number of studies have been performed that have examined the relationship of HDL levels and the incidence of coronary heart disease. Studies of kindreds with familial forms of low HDL-C show that many affected members have CHD. Among 19 prospective epidemiologic studies, 15 have shown a significant and strong inverse relationship between HDL-C and CHD, 3 have shown an inverse trend, and 1 showed no trend. In the Framingham Heart Study, the Lipid Research Clinics (LRC) Mortality Followup Study, the LRC Coronary Primary Prevention Trial, and the Multiple Risk Factor Intervention Trial quantitative analysis of the data was consistent with a 2 to 3 percent decrease in CHD risk for each 1 mg/dL increase in HDL-C level, after adjustment to control for other risk factors. Followup extended from 6 to 10 years, and similar results were found in men and women. The limited information available on interventions which increase HDL-C suggests that this has a favorable effect on CHD. In studies of atherosclerosis regression, examination of coronary angiographic changes following interventions which increased HDL-C have generally shown positive results. The concept that HDL may prevent the entry of cholesterol into the process of atherogenesis or even remove cholesterol from atherosclerotic lesions, socalled reverse cholesterol transport, has been supported by animal experiments. Two experiments suggest that affecting HDL may be beneficial. In one, HDL was infused into rabbits being fed atherogenic diets, and in the other, transgenic mice overexpressing human apoAI were fed atherogenic diets. In both cases, there was less rapid progression of atherosclerosis. However, there are still several unresolved issues. Unlike the situation with triglycerides, there is presently no information that examines HDL levels in relationship to alterations in coagulation factors. Not all individuals with inherited low HDL levels develop premature coronary heart disease. Subjects with genetic defects in the production of HDL have more CHD than

222 Angina

those with defects in the catabolism of HDL. The reasons for these variations in CHD incidence are poorly understood, but further investigation of such cases may shed light on the role of HDL in atherogenesis. It is apparent, as in most lipoprotein fractions, that HDL is a heterogeneous collection of particles of differing size and composition and that subpopulations of HDL are altered in many of the dyslipidemias. It is not known to what extent these alterations of HDL contribute to atherogenesis and if all interventions affect these fractions in a similar way. The conclusions reached by the panel are related to studies reviewed based on American and European populations. These conclusions may not be necessarily applicable to populations with a low incidence of CHD. Triglyceride Observational studies using case control methods in patients with CHD have consistently shown a strong association of increased triglyceride with CHD. Most prospective cohort studies similarly show a strong positive relationship between triglyceride and CHD, demonstrating a dose response relationship. However, some studies suggest a specific level must be achieved for increased risk. When these same cohort studies are subjected to multivariate analysis, controlling for other risk factors such as blood pressure, physical activity, and obesity, the effect of triglyceride is diminished. The addition of indicators of abnormal glucose metabolism or HDL-C either eliminates or significantly reduces triglyceride as an independent predictor for risk. One possible explanation for the variability of these data may be found in the heterogeneity of the triglyceride containing lipoprotein and the biological variability of the measurement. The measurement of a single fasting triglyceride may inadequately represent this lipid. Individual triglyceriderich lipoproteins, chylomicron remnants, intermediate density lipoproteins (IDL), very low density lipoproteins (VLDL), or particles of differing size and composition may be more closely related to CHD. Postprandial triglyceride may be more important than the fasting triglyceride levels, but little is known about this at the present time. In vitro studies find IDL, VLDL remnants, and other triglyceride-rich lipoproteins to increase foam cell production. Some studies of atherosclerotic lesions have observed concentrations of triglyceride approximately twice those seen in the normal arterial wall. The triglyceride level of more advanced lesions does not rise as do the contents of cholesterol and cholesterol esters. This suggests that triglyceride may be metabolized within the arterial wall. Currently there is no animal model in which isolated elevations and triglyceride produce arterial lesions.

Physical Activity and Cardiovascular Health 223

There are a number of genetic disorders with increased blood triglycerides. They may have either increased triglyceride synthesis or defects in removal. Many of these disorders (e.g., lipoprotein lipase deficiency and Apo-C-II deficiency) appear to have no increase in CHD despite elevated triglyceride levels. The VLDL and chylomicron particles of these patients are large and appear to lack atherogenic potential. However, other studies have reported premature CHD in hypertriglyceridemia, particularly when associated with hypertension or other lipid abnormalities characterized by small and apparently atherogenic VLDL and/or remnant particles as in familial combined hyperlipidemia and dysbetalipoproteinemia. In familial hypertriglyceridemia, some families have increased CHD, while others do not. Recent data connect triglyceride levels with alterations of the coagulation system. Increased triglyceride levels are associated with increases in several coagulation factors (VIIc, VIIIc, and Xc) and altered fibrinolytic factors (increased PAI-1 and decreased tPA activity). Lowering of triglyceride by diet or drugs may normalize these clotting factors. It is suggested that some of the deleterious effects of elevated triglyceride on CHD may be mediated through its effects on the clotting and fibrinolytic mechanisms. Clinical trials to specifically reduce triglyceride levels to prevent CHD have not been performed. Several trials in which the primary aim was to reduce LDL or total cholesterol have been done where triglyceride was measured. Four nonrandomized trials of lipid-lowering treatments measured triglyceride but failed to find any association with angiographic changes in coronary arteries. Of six randomized angiographic studies, five found no association despite triglyceride changes in all groups. One study demonstrated changes in lesions associated with triglyceride, HDL-C, and LDL-C. Four large trials with CHD endpoints measured triglyceride, but three failed to show any association of triglyceride with CHD outcomes despite significant reductions in the intervention groups. The Stockholm Ischaemic Heart Disease Secondary Prevention Study did find an association with triglyceride reduction. The inverse association of HDL-C with triglyceride is important in most circumstances. It is reasonable to infer that triglyceride plays an important role in the regulation of HDL metabolism. In this scenario, HDL would be the lipoprotein interactive with the plaque formation mechanisms, but triglyceride would play an important role in establishing the type, size, and quantity of HDL particles.

224 Angina

In prospective studies in which triglyceride has been considered jointly with HDL-C, LDL-C, total cholesterol, and other known CHD risk factors, multivariate statistical analyses generally have not shown triglyceride to be an independent risk factor for CHD. Because of a strong inverse correlation between triglyceride and HDL-C, relatively low precision of triglyceride measurements, and considerably higher variability of triglyceride values compared with cholesterol values, theoretical statistical analyses were recently performed. These analyses may underestimate the association between triglyceride and the risk of CHD. There is limited evidence from a recent prospective observational study (PROCAM Study) suggesting that risk of CHD increased for individuals with relatively high LDL-C and low HDL-C with increasing triglycerides. In a recent primary prevention trial (Helsinki Heart Study), a subgroup analysis of individuals with high LDL-C and triglyceride and low HDL-C exhibited the largest benefit in reducing CHD. This subgroup analysis may be due to chance and warrants further study. There have been no intervention studies designed to address the question of the association of elevated triglyceride with CHD stratified by levels of HDL-C, LDL-C, and total cholesterol while controlling for other known CHD risk factors. In summary, review of the information on HDL and CHD provides considerable support for a causal relationship. For triglyceride, the data are mixed; although strong associations are found in some studies, the evidence on a causal relation is still incomplete.

Prevention of Coronary Heart Disease The evidence most relevant to answer this question would consist of intervention trials with clinical or vascular imaging endpoints that demonstrated that reduction in very low density lipoproteins and/or elevations of HDL-C were associated with reduced clinical CHD events. These include fatal and nonfatal MI, angina, sudden death, need for coronary artery bypass graft surgery, angioplasty and other cardiovascular endpoints, or favorable changes in coronary lesions as evaluated by serial quantitative imaging of the coronary artery. Ideally, there would be quantitative correlations between the lipid-lipoprotein parameters and the study endpoints, and it would be shown that the lipoprotein alterations completely account for the favorable study endpoints. The data would be particularly convincing if total mortality also were favorably affected, and drug toxicity and drug side effects were acceptably low. Supporting data from appropriate experiments in animals would also be valuable.

Physical Activity and Cardiovascular Health 225

Several large-scale clinical trials involving both primary and secondary prevention have assessed the effects of lipid lowering on clinical coronary endpoints and have also measured total cholesterol, triglyceride, or HDL-C throughout the study. None of these trials was designed specifically to test the hypothesis that altering triglyceride or HDL-C concentrations would reduce coronary risk. Hence, none of the studies selected patients based solely on elevated triglyceride or low HDL-C. Instead, most studies sought to test the efficacy of lowering the LDL-C, and most subjects were chosen based on elevations of total cholesterol, LDL-C, or apolipoprotein B concentrations. Each of the interventions affected total cholesterol and/or LDL-C and one or more of the other components of the lipid profile. However, in only one of these studies, the Stockholm Ischaemic Heart Disease Secondary Prevention Study, was there a clear relationship between triglyceride levels in the treated group and beneficial change in CHD event rates. Since this study did not measure HDL levels, no conclusions could be drawn with regard to HDL. In the Lipid Research Clinics’ Coronary Primary Prevention Trial, the overall decline in CHD risk was 19 percent, 2 percent of which was attributable to an increase in HDL that was correlated with a 2 percent decline in CHD risk, and the benefit was greatest in those with a baseline HDL > 50 mg/dL. It should be noted that significant correlations were demonstrated also between lowering of LDL cholesterol and coronary risk. In the Helsinki Heart Study, a mean 12 percent rise in HDL-C and an 11 percent fall in LDL-C were both correlated with a 34 percent decline in CHD events. After correcting for HDL-C and LDL-C, no relationship between CHD events and triglyceride concentrations was found. Approximately 10 percent of the treated subjects had LDL-C/HDL-C ratios > 5 and triglyceride > 200 mg/dL. These patients had a 70 percent lowering of their CHD risk with gemfibrozil therapy, suggesting that a subgroup at especially high risk and particularly sensitive to therapy had been identified. The relative lowering of risk in other subgroups was considerably less. In a review of trials using angiographic endpoints employing randomization, interventions designed to alter lipoprotein levels caused small but generally favorable changes in coronary arteries (decreased progression, stabilization of lesions and possible regression in some cases, and less new lesion formation). These angiographic changes were associated with favorable outcome. However, attempts to correlate the favorable vascular changes to either total triglyceride reduction or HDL-C elevation have yielded no consistent trends. Although the evidence from clinical trials is insufficient to draw conclusions about the specific benefits of perturbing triglyceride and/or HDL levels,

226 Angina

lipid-lowering therapy is an effective strategy in CHD prevention. In most studies, the benefits are correlated with changes in LDL-C, but initial triglyceride and/or HDL concentrations play important modifying roles in determining the degree of benefits achieved. These modifying roles suggest that atherogenic and antiatherogenic subfractions may be present in VLDL and HDL fractions, respectively. At the present time these fractions are not being specifically measured when determinations of triglyceride and HDL-C concentrations are normally carried out, as is noted in our response to question 1.

Should Triglyceride and HDL Be Measured? Risk assessment using total cholesterol levels has proven valuable in identifying patients who are at elevated risk for atherosclerotic cardiovascular diseases. However, epidemiological data have demonstrated that a substantial percentage of patients who develop CHD have total cholesterol levels in the desirable range. Accordingly, HDL-cholesterol and triglyceride measurements have been proposed as additional methods to improve risk assessments. The panel recommends assay of HDL-C levels under the following circumstance: HDL-C measurement should be added to total cholesterol measurement when evaluating CHD risk in healthy individuals provided accuracy of measurement, appropriate counseling, and followup can be assured. The panel recommends assay of both HDL and triglyceride levels under the following circumstances: ·

To assess risks for progression of disease and development of additional cardiovascular complications in persons with known CHD.

·

To refine CHD risk assessment in those with increased total cholesterol (above the desirable range). Here, HDL-C and triglycerides should be measured to identify those who may have high HDL-C and desirable LDL-C and, therefore, be at low to average risk for CHD.

·

To refine CHD risk assessment in those with desirable total cholesterol who have 2 or more CHD risk factors (e.g., male sex, postmenopausal female, hypertension, family history, smoking, diabetes). In this setting, HDL-C and triglyceride should be measured to identify those who may have low HDL-C and/or high triglyceride and, therefore, actually be at additional risk for CHD.

Physical Activity and Cardiovascular Health 227

·

To refine CHD risk assessment in patients with other disorders which may be associated with increased triglyceride and are known to be associated with increased CHD risk (e.g., diabetes, peripheral vascular disease, hypertension, central obesity, chronic renal disease).

·

In patients with lactescent serum, lipemia retinalis, xanthomata, or pancreatitis, to determine the presence of familial hyperlipidemic disorders and/or the likelihood for recurrence of pancreatitis and to follow triglyceride response to treatment in such cases when triglyceride is elevated, triglyceride should be measured.

·

To follow results of nonpharmacologic and/or pharmacologic therapy directed toward reductions of triglyceride and/or increases of HDL-C in order to assess treatment effect.

Measurement Considerations The extent to which HDL-C and triglyceride levels can be used to assess risk for CHD depends, among other things, on the accuracy and reliability with which these plasma lipids can be measured. Imprecision in these measurements relates to both biologic and analytical variations. The biologic variation for HDL-C measurements, expressed as coefficient of variation (CV), is approximately 7 to 8 percent, and the analytical variation is approximately 6 percent (CV). For triglyceride, the biologic variation approximates 20 percent (CV) and analytical variation, 5 percent (CV). In addition, the variability is dependent upon prior alcohol intake, posture, concomitant medications and hormones, prior exercise status, diet, menstrual cycle, time of day (a.m.), and sample collection (e.g., concentration of anticoagulant in the blood filled tube and storage). Standardizing these factors will reduce the variability. Accordingly, using current techniques for HDL and triglyceride analysis, at least two, ideally three, samples, taken in the fasting state at least 1 week apart, are generally recommended in order to enhance precision before treatment decisions are finalized.

Dietary, Drug, and Other Hygienic Treatments Lifestyle factors that significantly aggravate hypertriglyceri-demia and low HDL-C levels are obesity, smoking, and sedentary lifestyle. Thus, diet and weight control, exercise, and smoking cessation must be the emphasis of treatment for elevated triglyceride and low HDL-C levels. Treatment should be individualized and targeted to the causative factor(s).

228 Angina

A National Cholesterol Education Program/American Heart Association Step-One diet is recommended for all patients with elevated triglycerides. Some patients will require a Step-Two diet to achieve further modifications in plasma lipids. A Step-One diet provides 30 percent of calories from fat, less than 10 percent of calories from saturated fatty acids, up to 10 percent of calories from polyunsaturated fatty acids, up to 15 percent of calories from monounsaturated fatty acids, and < 300 mg of cholesterol. A Step-Two diet provides < 7 percent of calories from saturated fatty acids, and < 200 mg of cholesterol. These diets are effective in achieving a plasma total and LDL-C lowering, facilitate achieving and maintaining a healthy weight, and aid in managing elevated triglycerides. Obesity/Overweight and Excess Calories Obesity/overweight and excess calories frequently are associated with hypertriglyceridemia and low HDL-C levels. Frequently, weight loss alone can significantly decrease plasma triglycerides and increase HDL-C levels. Achieving and maintaining a healthy weight by diet (calorie control) and regular exercise are important in managing elevated triglyceride and low HDL-C levels. Frequently, weight loss alone normalizes plasma triglycerides; combined with a program of regular exercise, HDL-C levels may increase 10 to 20 percent.

Alcohol Alcohol increases plasma triglycerides in some patients and increases HDLC. In patients with very high triglycerides, alcohol should be eliminated. Because of inherent problems, as well as its effects on triglycerides, alcohol use to raise HDL-C is not recommended. Carbohydrate A high carbohydrate diet has been shown to increase plasma triglycerides and decrease HDL-C levels. These diets lead to the production of large buoyant VLDL particles, which are thought to be less atherogenic compared to dense VLDL particles. In societies that have a high carbohydrate diet and a low incidence of CHD, plasma triglycerides are slightly higher and both LDL-C and HDL-C are lower than in societies that consume a Western diet. Thus, low HDL-C levels of themselves may not be deleterious under these circumstances. The Step-One and Step-Two diets should emphasize complex

Physical Activity and Cardiovascular Health 229

carbohydrates and fiber for the treatment of elevated triglycerides. Some patients may initially experience a slight increase in plasma triglycerides on a Step-One and Step-Two diet; however, these patients should have more favorable lipid/lipoprotein profiles (i.e., lower plasma total cholesterol and LDL-C levels) and therefore a lower risk of CHD.

Fish and Fish Oil From population studies, diets high in fish are associated with reduced CHD risk. Fish oils and omega-3 fatty acids result in decreased triglycerides, and may increase LDL-C and/or apolipoprotein B level(s). They also impair clotting and diabetic control. Omega-3 fatty acids, in large amounts, may reduce excessive triglyceride levels that do not respond adequately to recommended dietary therapy.

Exercise Exercise increases HDL-C and decreases plasma triglycerides and the risk of CHD. Intervention studies have shown that there is a dose-response relationship between HDL-C levels and the amount (frequency, intensity, duration) of exercise. In general, intervention studies report a 10 to 20 percent increase in HDL-C in response to an exercise program. The decrease in HDL-C in response to a diet that is lower in total fat, saturated fat, and cholesterol can be prevented/attenuated by a regular exercise program. A program of regular exercise is important in achieving and maintaining a healthy weight.

Cigarette Smoking Cigarette smoking decreases HDL-C and is a powerful risk factor for coronary heart disease. A recent study suggests that passive smoking also decreases HDL-C. Smoking cessation increases HDL-C and reduces CHD risk.

Summary of Hygienic Therapy The primary therapy for the treatment of elevated triglyceride and low HDLC levels is diet and weight control, exercise, and smoking cessation. Hygienic measures always should be used first, and rigorous intervention is

230 Angina

recommended. For many patients, triglycerides and HDL-C can be normalized by these interventions alone. Patients are likely to benefit from the services of health professionals such as registered dieticians and other qualified nutritionists, exercise physiologists, and health educators. Third-party reimbursement for these services is recommended to decrease the significant barriers that exist in enabling patients to realize the full benefits of hygienic therapy.

Pharmacologic Therapy Pharmacologic therapy of hypertriglyceridemia and low HDL is relegated to a secondary role for the reasons indicated above. All medications have side effects, and potential risks must be balanced with potential for benefit before their use can be justified. Oral estrogens alter plasma lipoproteins and, from extensive observational studies in postmenopausal women, appear to reduce coronary heart disease by approximately 50 percent. In usual clinical doses, they lower LDL-C and increase HDL and triglycerides. Information is lacking on the effect of estrogen-induced changes in HDL subfractions, apolipoproteins, or the risks of CHD when triglyceride levels are increased. There is a risk of increased incidence of endometrial cancer and possible increase in the risk of breast cancer. Although extensive observational data indicate that there is benefit of estrogens in CHD, the most common cause of death in postmenopausal women, evidence from randomized prospective clinical trials demonstrating benefit in coronary heart disease is lacking. Nicotinic acid decreases triglycerides in proportion to their elevation and is very effective in increasing low HDL. There is a relative contraindication for use in patients with noninsulin-dependent diabetes. Niacin is a first choice when drugs are required because of its low cost and its efficacy in altering multiple lipid fractions. The combination of diet, bile acid sequestrants, and niacin reduced progression of atherosclerosis and appearance of new lesions in patients with and without coronary bypass grafts. Fibric acid derivatives decrease triglycerides and increased HDL-C. One fibric acid derivative, gemfibrozil, has been associated with reduced risk of CHD in patients with mixed hyperlipidemia and low HDL levels. Bile acid sequestrants induce a small increment in triglycerides and in HDL. Their use is not recommended in patients with significant hypertriglyceridemia.

Physical Activity and Cardiovascular Health 231

HMGCoA reductase inhibitors decrease triglycerides in the intermediate levels and increase HDL in patients with hypercholesterolemia and low HDL. They have modest effectiveness on higher triglyceride levels.

High-Risk Individuals and the General Population Rationale The rationale for treatment of hypertriglyceridemia is based on observational studies in which triglyceride levels correlated directly with coronary heart disease. In addition, certain genetic forms of hyperlipidemia--such as familial combined hyperlipidemia, familial type 3 hyperlipidemia, and some families with familial hypertriglyceridemia--are associated with an increased incidence of CHD. In these disorders, VLDL or its remnants or remnants of chylomicrons accumulate in plasma and are thought to result in atheroma formation. Hypertriglyceridemia is also frequently associated with other abnormalities which may predispose to atherosclerosis. These include low HDL-C levels, an increased number of small dense LDL particles, an increased concentration of postprandial lipoproteins, and altered levels of coagulation factors that may either favor thrombosis or inhibit fibrinolysis. Furthermore, patients with very high triglyceride levels (generally exceeding 1,000 mg/dL) are prone to develop pancreatitis. The rationale for treating low HDL-C is also based on observational data relating cardiovascular risk inversely to HDL-C levels. In addition, results of several intervention trials indicate that the benefit of treatment was partially related to an increase in HDL-C. The hygienic measures and drugs that reduce triglycerides and/or raise HDL-C were discussed in the previous section.

High Triglyceride or Low HDL-C and Cardiovascular Disease Risk The previous consensus development panel on hypertriglyceridemia classified triglyceride levels into distinct hypertriglyceridemia (triglyceride level > 500 mg/dL) and borderline hypertriglyceri-demia (triglyceride level 250 to 500 mg/dL). The current consensus panel found no clear evidence to indicate a need for change in this classification. With regard to HDL-C, a range of levels correlates inversely with CHD risk, and the panel arbitrarily selected < 35 mg/dL as the cut-point for identifying individuals with very high risk. This level may be too low in women and possibly other specific

232 Angina

subpopulations, but it conforms with existing National Cholesterol Education Program (NCEP) guidelines. No compelling data were identified which would currently dictate a change in the use of this HDL-C cut-point. Use of Triglyceride and HDL-C in the Assessment of Patients The metabolism of the lipoprotein classes in plasma is interrelated, and patients frequently display abnormalities in more than one lipoprotein. Therefore, the triglyceride and HDL-C levels cannot be interpreted in the absence of the LDL-C level. Since the LDL-C is essential in cardiovascular risk assessment, a reasonable approach to the evaluation of HDL-C and triglyceride levels in patients is to include the LDL-C level in making therapeutic decisions as recommended by the ATP of the NCEP. There is general agreement with the NCEP guidelines to the effect that persons with elevations of LDL-C greater than 160 mg/dL refractory to nondrug therapies may require drug treatment. The other factors entering into a decision to use drugs include the presence of CHD or other CHD risk factors such as low HDL-C, family history for CHD, diabetes mellitus, hypertension, cigarette smoking, male gender, and obesity. Accumulating evidence suggests that the postmenopausal state in women should also be considered a CHD risk factor. Current data from the Helsinki Heart Study and the PROCAM Study indicate that elevated triglyceride concentrations may also contribute to risk assessment and hence should be considered in making therapeutic decisions. In the absence of any of these risk factors, CHD, or in the presence of a very high HDL-C level, drug therapy is not indicated for borderline high risk LDL-C levels (130-160 mg/dL). There is no consensus for the use of drug treatment in patients with borderline hypertriglyceridemia and low HDL-C levels in the presence of a desirable LDL-C level. There is strong consensus that hygienic approaches (diet, exercise, smoking cessation, weight loss) should be employed. Drug treatment should be considered in cases where hygienic approaches fail, and CHD or a strong coronary risk profile is present. No intervention trials to test this approach (lowering triglyceride and/or raising HDL-C with drugs) have been reported in this type of patient. Distinct hypertriglyceridemia (500 mg/dL and above) should be managed initially with hygienic measures. If hypertriglyceridemia persists, drug therapy is warranted to reduce the risk for pancreatitis. When a history of pancreatitis is already present, drug treatment should be considered as the initial therapy in conjunction with the hygienic measures. Patients who fail

Physical Activity and Cardiovascular Health 233

to respond to drug therapy may have lipoprotein lipase deficiency or apolipoprotein C-II deficiency and require expert evaluation. Very low or absent HDL-C levels in patients with desirable LDL-C and high triglyceride levels probably represent rare genetic disorders that require expert evaluation. Often these patients have genetic mutations affecting one or more of the apolipoproteins in HDL particles. There is no specific therapy at this time for these patients. Primary hypoalphalipoproteinemia is a relatively uncommon familial disorder with low HDL-C levels and generally normal LDL-C and triglyceride levels. These patients appear to be at increased risk for CHD. Therapy should include hygienic measures and control of coexisting CHD risk factors. Drugs that ordinarily raise HDL-C may be ineffective in these patients. Therefore, some experts have taken the approach that therapy should be directed toward lowering the LDL-C concentrations. However, it must be noted that no intervention trials have been performed to test the validity of this approach. Beyond the clinical situations enumerated above, there is no consensus for treating mild non-familial hypertriglyceridemia and/or low HDL-C levels with drugs in the absence of other major risk factors.

Questions for Continuing Research ·

We encourage the development of precise, accurate, rapid, and inexpensive measurements of plasma lipid concentrations and other atherogenic particles.

·

More research is needed to identify and quantify atherogenic and antiatherogenic subfractions which may be present in VLDL and HDL.

·

Additional studies are needed to determine the interrelationships of altered lipid metabolism and thrombosis in atherogenesis.

·

Additional studies are desirable to provide information on the atherogenic effects of high triglycerides and low HDL in animal models. Development of appropriate animal models is encouraged.

·

Primary and secondary prevention trials need to examine the benefits of decreasing triglyceride and raising HDL-C in patients selected on the basis of high triglyceride and/or low HDL levels.

·

Studies should be initiated to determine the association of CHD with cholesterol and lipoprotein fractions in minority populations.

234 Angina

·

Additional studies are needed to assess the impact of lifestyle modification on the elevation of low HDL-C. The effects of estrogen and progesterone use on HDL subfractions, apolipoproteins, Lp(a), and the effects of these lipids on CHD risk in women is needed.

·

We recommend the development of methods to make hygienic intervention more effective to larger segments of our society, including those with low literacy skills.

·

We wish to foster the development of methods, preferably noninvasive, to image the vascular wall in order to characterize plaque composition and quantify its size and distribution.

·

Further studies are needed to evaluate the effects of diet on plasma lipoproteins, their composition, production and clearance, and measures of hemostasis.

Conclusions Considerable evidence is available suggesting that a causal association exists between the presence of a low plasma HDL cholesterol and the subsequent development of coronary heart disease. Current evidence does not allow one to conclude that comparable causality exists between the presence of high levels of plasma triglyceride and coronary heart disease. Nevertheless, triglyceride-rich lipoproteins can be atherogenic. Furthermore, elevated triglycerides produce increases in several clotting factors and decrease fibrinolytic activity which may contribute over time to the atherosclerotic process. Triglyceride levels correlate in many prospective studies with coronary events. However, when multivariate statistical analyses are carried out that adjust for HDL-C, LDL-C, and total cholesterol and other risk factors, this correlation is frequently lost. There is some limited evidence, nevertheless, that suggests that the risk of CHD increases as triglyceride increases in patients exhibiting high levels of total or LDL cholesterol and low levels of HDL-cholesterol. Evidence from existing clinical trials is inadequate to conclude that lowering triglyceride will decrease the risk of CHD. Reduction in CHD frequently occurs when patients with elevated LDL cholesterol are treated with hygienic measures and/or drugs. It seems desirable based on secondary prevention trials and angiographic studies of coronary atherosclerosis to treat CHD patients with low HDL and elevated triglyceride levels even in

Physical Activity and Cardiovascular Health 235

the presence of a desirable total cholesterol. Such treatment should begin with hygienic measures but drug use may be entertained if these measures prove ineffective. The panel recommends that HDL determinations should accompany measurements of total cholesterol when healthy individuals are being assessed for CHD risk. The panel cautions, however, that this be done in locations where accuracy of measurement, appropriate counseling, and followup can be assured. This is particularly important because of the increased biologic and analytical variation inherent in its measurement. The panel also recommends that HDL-C and triglyceride levels be determined in healthy individuals with high total cholesterol and in those who have two or more of the known CHD risk factors. Patients with diabetes, central obesity, peripheral vascular disease, hypertension, and chronic renal disease, which are known to be associated with an increased risk of CHD, should have triglyceride levels measured. Triglycerides should also be measured where familial hyperlipidemic disorders are suspected and to follow the results of therapy when patients are treated for elevated triglycerides. Finally, HDL-C and triglycerides should accompany measurements of total cholesterol in patients with known CHD. Hygienic measures should always be employed when triglycerides are elevated or HDL cholesterol is low regardless of total cholesterol. Drugs, however, should be used sparingly under these circumstances in the absence of an elevation of LDL cholesterol in individuals without known CHD. It is clear that many important questions remain unanswered regarding the impact of these two major lipid fractions.

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Aorta: Blood vessel that delivers oxygen-rich blood from the left ventricle to the body; it is the largest blood vessel in the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Colestipol: Highly crosslinked and insoluble basic anion exchange resin

236 Angina

used as anticholesteremic. It may also may reduce triglyceride levels. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Radiography: The making of film records (radiographs) of internal structures of the body by passage of x-rays or gamma rays through the body to act on specially sensitized film. [EU]

Physical Activity and Cardiovascular Health 237

APPENDIX F. LOWERING BLOOD CHOLESTEROL TO PREVENT HEART DISEASE Overview NIH Consensus Development Conferences are convened to evaluate available scientific information and resolve safety and efficacy issues related to biomedical technology. The resultant NIH Consensus Statements are intended to advance understanding of the technology or issue in question and to be useful to health professionals and the public.58 Each NIH consensus statement is the product of an independent, non-Federal panel of experts and is based on the panel’s assessment of medical knowledge available at the time the statement was written. Therefore, a consensus statement provides a “snapshot in time” of the state of knowledge of the conference topic. The NIH makes the following caveat: “When reading or downloading NIH consensus statements, keep in mind that new knowledge is inevitably accumulating through medical research. Nevertheless, each NIH consensus statement is retained on this website in its original form as a record of the NIH Consensus Development Program.”59 The following concensus statement was posted on the NIH site and not indicated as “out of date” in March 2002. It was originally published, however, in December 1984.60

This paragraph has been adapted from the NIH: http://odp.od.nih.gov/consensus/cons/cons.htm. 59 Adapted from the NIH: http://odp.od.nih.gov/consensus/cons/consdate.htm. 60 Lowering Blood Cholesterol To Prevent Heart Disease. NIH Consensus Statement Online 1984 Dec 10-12 [cited 2002 February 15]; 5(7):1-11. http://consensus.nih.gov/cons/047/047_statement.htm 58

238 Angina

What Is Coronary Heart Disease? Coronary heart disease is responsible for more than 550,000 deaths in the United States each year. It is responsible for more deaths than all forms of cancer combined. There are over 5.4 million Americans with symptomatic coronary heart disease and a large number of others with undiagnosed coronary disease, many of them young and highly productive. It has been estimated that coronary heart disease costs the United States over $60 billion a year in direct and indirect costs. Coronary heart disease is due to atherosclerosis, a slowly progressive disease of the large arteries that begins early in life but rarely produces symptoms until middle age. Often the disease goes undetected until the time of the first heart attack, and this first heart attack is often fatal. Modern methods of treatment have improved greatly the outlook for patients having heart attacks, but major progress in our battle against this number one killer must rest on finding preventive measures. A number of risk factors have been identified as strongly associated with coronary heart disease. Cigarette smoking, high blood pressure, and high blood cholesterol are the most clearly established of these factors. Risk is greater in men, increases with age, and has a strong genetic component. Obesity, diabetes mellitus, physical inactivity, and behavior pattern are also risk factors. A large body of evidence of many kinds links elevated blood cholesterol levels to coronary heart disease. However, some doubt remains about the strength of the evidence for a cause-and-effect relationship. Questions remain regarding the exact relationship between blood cholesterol and heart attacks and the steps that should be taken to diagnose and treat elevated blood cholesterol levels. To resolve some of these questions, the National Heart, Lung, and Blood Institute and the NIH Office of Medical Applications of Research convened a Consensus Development Conference on Lowering Blood Cholesterol to Prevent Heart Disease on December 10-12, 1984. After hearing a series of expert presentations and reviewing all of the available data, a consensus panel of lipoprotein experts, cardiologists, primary care physicians, epidemiologists, biomedical scientists, biostatisticians, experts in preventive medicine, and lay representatives considered the evidence and agreed on answers to the following questions:

Physical Activity and Cardiovascular Health 239

·

Is the relationship between blood cholesterol levels and coronary heart disease causal?

·

Will reduction of blood cholesterol levels help prevent coronary heart disease?

·

Under what circumstances and at what level of blood cholesterol should dietary or drug treatment be started?

·

Should an attempt be made to reduce the blood cholesterol levels of the general population?

·

What research directions should be pursued on the relationship between blood cholesterol and coronary heart disease?

Panel’s Conclusions Elevated blood cholesterol level is a major cause of coronary artery disease. It has been established beyond a reasonable doubt that lowering definitely elevated blood cholesterol levels (specifically blood levels of low-density lipoprotein cholesterol) will reduce the risk of heart attacks due to coronary heart disease. This has been demonstrated most conclusively in men with elevated blood cholesterol levels, but much evidence justifies the conclusion that similar protection will be afforded in women with elevated levels. After careful review of genetic, experimental, epidemiologic, and clinical trial evidence, we recommend treatment of individuals with blood cholesterol levels above the 75th percentile (upper 25 percent of values). Further, we are persuaded that the blood cholesterol level of most Americans is undesirably high, in large part because of our high dietary intake of calories, saturated fat, and cholesterol. In countries with diets lower in these constituents, blood cholesterol levels are lower, and coronary heart disease is less common. There is no doubt that appropriate changes in our diet will reduce blood cholesterol levels. Epidemiologic data and over a dozen clinical trials allow us to predict with reasonable assurance that such a measure will afford significant protection against coronary heart disease. For these reasons we recommend that: ·

Individuals with high-risk blood cholesterol levels (values above the 90th percentile) be treated intensively by dietary means under the guidance of a physician, dietitian, or other health professional; if response to diet is inadequate, appropriate drugs should be added to the treatment regimen. Guidelines for children are somewhat different, as discussed below.

240 Angina

·

Adults with moderate-risk blood cholesterol levels (values between the 75th and 90th percentiles) be treated intensively by dietary means, especially if additional risk factors are present. Only a small proportion should require drug treatment.

·

All Americans (except children under 2 years of age) be advised to adopt a diet that reduces total dietary fat intake from the current level of about 40 percent of total calories to 30 percent of total calories, reduces saturated fat intake to less than 10 percent of total calories, increases polyunsaturated fat intake but to no more than 10 percent of total calories, and reduces daily cholesterol intake to 250 to 300 mg or less.

·

Intake of total calories be reduced, if necessary, to correct obesity and adjusted to maintain ideal body weight. A program of regular moderatelevel exercise will be helpful in this connection.

·

In individuals with elevated blood cholesterol, special attention be given to the management of other risk factors (hypertension, cigarette smoking, diabetes, and physical inactivity).

These dietary recommendations are similar to those of the American Heart Association and the Inter-Society Commission for Heart Disease Resources. We further recommend that: ·

New and expanded programs be planned and initiated soon to educate physicians, other health professionals, and the public to the significance of elevated blood cholesterol and the importance of treating it. We recommend that the National Heart, Lung, and Blood Institute provide the focus for development of plans for a National Cholesterol Education Program that would enlist participation by and contributions from all interested organizations at national, state, and local levels.

·

The food industry be encouraged to continue and intensify efforts to develop and market foods that will make it easier for individuals to adhere to the recommended diets and that school food services and restaurants serve meals consistent with these dietary recommendations.

·

Food labeling should include the specific source or sources of fat, total fat, saturated and polyunsaturated fat, and cholesterol content as well as other nutritional information. The public should be educated on how to use this information to achieve dietary aims.

·

All physicians be encouraged to include whenever possible a blood cholesterol measurement on every adult patient when that patient is first seen; to ensure reliability of data, we recommend steps to improve and standardize methods for cholesterol measurement in clinical laboratories.

Physical Activity and Cardiovascular Health 241

·

Further research be encouraged to compare the effectiveness and safety of currently recommended diets with that of alternative diets; to study human behavior as it relates to food choices and adherence to diets; to develop more effective, better tolerated, safer, and more economical drugs for lowering blood cholesterol levels; to assess the effectiveness of medical and surgical treatment of high blood cholesterol levels in patients with established clinical coronary artery disease; to develop more precise and sensitive noninvasive artery imaging methods; to apply basic cell and molecular biology to increase our understanding of lipoprotein metabolism (particularly the role of HDL as a protective factor) and artery wall metabolism as they relate to coronary heart disease.

·

Plans be developed that will permit assessment of the impact of the changes recommended here as implementation proceeds and provide the basis for changes when and where appropriate.

Causal Relationship: Blood Cholesterol Levels and Coronary Heart Disease The evidence supporting a causal relationship between blood cholesterol levels and coronary heart disease comes from a wealth of congruent results of genetic, experimental pathologic, epidemiologic, and intervention studies. These data establish beyond any reasonable doubt the close relationship between elevated blood cholesterol levels (as measured in serum or plasma) and coronary heart disease. At the same time, it is equally clear that an elevated blood cholesterol level is not the only cause of coronary heart disease. Hypertension, cigarette smoking, diabetes mellitus, obesity, and physical inactivity along with a number of other risk factors such as age, sex, and family history are important contributing causes. There probably are other undiscovered contributing causes. However, we shall confine ourselves here primarily to a discussion of elevated blood cholesterol. It is now firmly established that all cholesterol is carried in the bloodstream in several protein-lipid combinations known as lipoproteins and that most of the blood cholesterol in humans is carried by specific low-density lipoproteins (LDL). Some is also present in high-density lipoproteins (HDL) and in very low-density lipoproteins (VLDL). The LDL particles, when present in excess in the blood, are deposited in the tissues and form a major part of a buildup in the artery wall to form atherosclerotic plaque. Atherosclerosis narrows the channels of the coronary arteries, the vessels that furnish the major blood supply to the heart muscle.

242 Angina

Genetic Evidence Severe coronary heart disease can result from high blood cholesterol levels in the absence of any other contributing risk factors. This is clearly demonstrated by the accelerated and clinically catastrophic coronary heart disease in children with inherited hypercholesterolemia in its most severe form. These children lack the specific receptor that normally removes LDL from the blood, and as a result, they have very high LDL cholesterol levels from birth. They frequently suffer severe coronary heart disease, and death may occur even in childhood. Careful study of these diseased arteries reveals large quantities of cholesterol in the plaques. The LDL receptor normally plays a critical role in regulating blood cholesterol levels in all mammals, including humans. It has been purified and fully characterized. Studies suggest that a number of cases of clinically important coronary heart disease with less severe elevations of blood cholesterol may be explained by partial deficiencies of functioning LDL receptors, deficiencies induced by dietary and lifestyle factors. Thus, the high blood cholesterol in these patients has a similar basis to that in inherited hypercholesterolemia and, while less severe, probably has the same implications.

Experimental Pathology (Animal Model) Evidence With improved use of the many existing animal models, a number of very important relationships between blood cholesterol, atherosclerosis, and coronary heart disease have been demonstrated: ·

Many species (including several nonhuman primates) develop atherosclerosis when fed diets that raise their blood cholesterol levels.

·

Studies over time demonstrate that hypercholesterolemic monkeys (and other species) develop intimal lesions that progress from fatty streaks to typical raised plaques to complicated ulcerated plaques resembling those seen in humans suffering from coronary heart disease.

·

Hypercholesterolemia augments experimental atherosclerosis when arterial “injury” is present.

·

Severe atherosclerosis in rhesus monkeys, usually a progressive process, regresses when the blood cholesterol is lowered substantially for an extended period by diet or by drugs.

Physical Activity and Cardiovascular Health 243

Animal studies thus offer strong and persuasive evidence supporting the causal relationship between blood cholesterol and atherosclerosis.

Epidemiologic Evidence A large body of epidemiologic evidence supports the direct relationship between blood cholesterol levels and coronary heart disease: ·

Comparisons among various populations throughout the world reveal a direct correlation between blood cholesterol levels and the occurrence of coronary heart disease; no population has been reported with a high rate of coronary heart disease and low blood cholesterol levels.

·

People who have migrated to another country with a higher average blood cholesterol level gradually acquire the dietary habits, blood cholesterol concentration, and coronary heart disease rates of their new country of residence.

·

Severity and frequency of raised plaques in the aorta and coronary arteries are strongly correlated with blood cholesterol levels.

·

Populations experiencing severe dietary (especially fat) limitations and weight loss have been shown to have less atherosclerosis, coronary heart disease, and fewer heart attacks.

·

Prospective studies such as the Framingham study have shown that elevated blood cholesterol levels in healthy people predict the future occurrence of coronary heart disease.

·

Evidence emerging from multiple clinical trials, reviewed in the next section, clearly indicates that lowering blood cholesterol levels in patients with hypercholesterolemia decreases the likelihood of fatal and nonfatal coronary heart disease.

Thus, the evidence obtained from genetic, experimental, epidemiologic, and clinical intervention investigations overwhelmingly supports a causal relationship between blood cholesterol levels and coronary heart disease.

Prevention of Coronary Heart Disease? Our conclusion that reduction of blood cholesterol levels will reduce the rate of coronary heart disease is based partly on the evidence for cause-and-effect presented above and partly on the direct evidence from clinical trials noted below.

244 Angina

First, metabolic ward studies establish beyond reasonable doubt three dietary maneuvers that lower blood cholesterol levels: reducing the saturated fat content, increasing the polyunsaturated fat content, and reducing the cholesterol content. Second, a number of drugs have been developed that lower blood cholesterol levels. The issue of whether these interventions also influence coronary heart disease events has been more challenging. In previous years, more than a dozen randomized trials of the effects of fatcontrolled diets or drugs have been reported. Most showed some decrease in coronary heart disease event rates in the treated group, and the dietary trials carried out by Dayton et al. and by Leren et al. were particularly suggestive, producing 23 percent and 35 percent reductions in the incidence of coronary heart disease. However, no study considered individually could be regarded as conclusive: the sample sizes were too small, and there were in some cases unanticipated increases in non-cardiovascular deaths, although these were not statistically significant. An aggregate analysis of all unifactor bloodcholesterol-lowering trials, while not revealing an effect on total mortality, does indicate that coronary heart disease rates can be reduced by reduction of blood cholesterol levels. These findings have been extended by two recently reported randomized and blinded clinical trials of the efficacy of the cholesterol-lowering drug, cholestyramine. One of these studies, the Lipid Research Clinics Coronary Primary Prevention Trial, showed a statistically significant 19 percent reduction in the combined rate of fatal and nonfatal coronary heart disease in association with a 9 percent decrease in blood cholesterol level. The other study, the NHLBI Type II Coronary Intervention Study, showed a reduction in the angiographic progression of coronary artery disease. In addition, a third trial (the Coronary Drug Project) has recently presented information extending the earlier published finding that the use of nicotinic acid lowers the rate of recurrent coronary heart disease by demonstrating in long-term followup a decrease in overall mortality. These findings, taken in conjunction with the results of the earlier studies, permit the conclusion that reduction of blood cholesterol level in people with relatively high initial levels will reduce the rate of coronary heart disease. The clinical trials are too limited to settle the issue of effects on overall mortality. However, the complete set of evidence, which includes information derived from animal, pathophysiological, metabolic, and epidemiologic studies, makes it reasonable to presume that the reduction in

Physical Activity and Cardiovascular Health 245

coronary heart disease incidence will be accompanied by a reduction in overall mortality. The magnitude of the reduction in coronary heart disease risk can be estimated from these clinical trials; they indicate that each 1 percent reduction in blood cholesterol level yields approximately a 2 percent reduction in coronary heart disease rates. This is remarkably similar to the magnitude of the beneficial outcome predicted from observational epidemiologic studies. Thus, for example, a 5 percent reduction in blood cholesterol level resulting from the diets recommended below should reduce coronary heart disease rates by 10 percent. The absolute magnitude of this benefit should be greater in patients at high risk because of existing coronary heart disease or the presence of other risk factors such as cigarette smoking and hypertension. Reductions in disease rates of as much as 50 percent may be achievable in high-risk cholesterol patients who adhere well to a combination of effective drug treatment and a fat-controlled diet.

Should Dietary or Drug Treatment What Is Hypercholesterolemia? A precise definition of hypercholesterolemia (an abnormally high blood cholesterol level) is difficult to establish. Often, an abnormally high level of a biologic substance is considered to be that level above which are found the upper 5 percent of the population (the 95th percentile). However, the use of this criterion in defining “normal” values for blood cholesterol levels in the United States is unreasonable; coronary heart disease is our major cause of death and, in part at least, because a large fraction of our population probably has too high a blood cholesterol level. A review of available data suggests that levels above 200 and 230 mg/dl are associated with an increased risk of developing premature coronary heart disease. It is staggering to realize that this represents about 50 percent of the adult population of the United States. The consensus panel has chosen to define two levels of hypercholesterolemia, both of which are associated with an increased coronary heart disease risk, and both of which should be treated.

High-Risk Blood Cholesterol (Severe Hypercholesterolemia) This category is defined as values at approximately the 90th percentile or above as determined by the Lipid Research Clinics Prevalence Study. It will include individuals with hereditary forms of high blood cholesterol and will

246 Angina

require the most aggressive treatment. Withholding treatment subjects these individuals to unnecessary risk.

Moderate-Risk Blood Cholesterol (Moderate Hypercholesterolemia) This category is defined as values approximately between the 75th to 90th percentiles. It includes large numbers of people whose elevated blood cholesterol is due, in part, to their diet. The intensity of treatment is guided by the clinical and family history and the presence of other risk factors predisposing to coronary heart disease.

Values for Selecting Adults at Moderate and High Risk Requiring Treatment Moderate Risk Age 20-29 Greater than 200 mg/dl (5.17 mM) mg/dl (5.69 mM) 30-39 Greater than 220 mg/dl (5.69 mM) mg/dl (6.21 mM) 40 and over Greater than 240 mg/dl (6.21 mM) mg/dl (6.72M)

High Risk Greater than

220

Greater

than

240

Greater

than

260

How Should Adults with Hypercholesterolemia Be Treated? The presence of high-risk and moderate-risk blood cholesterol should be confirmed by a repeat analysis. Although the initial sample may be obtained nonfasting, the repeat analysis should be obtained after an overnight fast so that a valid triglyceride level also can be determined. After the secondary causes for hypercholesterolemia (e.g., hypothyroidism, nephrotic syndrome, dysproteinemias, diabetes mellitus, and obstructive liver disease) have been excluded, the primary cause should be evaluated. This includes family screening to detect the hereditary forms of elevated blood cholesterol and to identify other family members needing treatment. Measurement of HDL cholesterol is often helpful to determine if the elevated blood cholesterol is due to high levels of HDL (which is associated with a lower risk of coronary heart disease). In addition, a low HDL cholesterol (an independent risk factor) might guide a physician to be more aggressive in treatment of individuals with high or moderately high blood cholesterol.

Physical Activity and Cardiovascular Health 247

Diet Therapy The first step in the treatment of high-risk and moderate-risk blood cholesterol is diet therapy and caloric restriction for weight normalization in the overweight. Weight loss may reduce blood cholesterol, and a moderate level of physical exercise may be helpful in this regard. The dietary approach should be to lower total fat, saturated fat, and cholesterol consumption. The following guidelines are generally consistent with those of the American Heart Association and the Atherosclerosis Study Group of the Inter-Society Commission for Heart Disease Resources. We recommend a diet composed of approximately 30 percent of the caloric intake from fats and no more than 250 to 300 mg of cholesterol a day. An essential consideration is a reduction of the total saturated fat intake to 10 percent or less of total calories. It is recommended that polyunsaturated fat intake be increased but to no more than 10 percent of total calories. These changes can be readily made while maintaining intake of protein, vitamins, and minerals to satisfy the Recommended Dietary Allowances of the Food and Nutrition Board of the National Research Council. Insufficient response to this diet may necessitate further restrictions of total fat to 20 to 25 percent of calories with saturated fat comprising 6 to 8 percent of the calories. The dietary cholesterol should be lowered to 150 to 200 mg/day (equivalent to American Heart Association Phases II and III diets). The use of diet as a primary mode of therapy requires a major effort on the part of physicians, nutritionists, dietitians, and other health professionals. Lifestyle changes are difficult without adequate instruction, motivation, and encouragement. Education of physicians, as well as the general public, as to the value of reductions in dietary saturated fat and cholesterol will assist not only with treatment of patients with high- or moderate-risk blood cholesterol but also in achieving the goal of reducing the blood cholesterol levels of our entire adult population to less than 200 mg/dl (less than 180 mg/dl in those under age 30).

Drug Therapy Drug therapy should be used only after a careful trial of diet modification using the most rigorous diet appropriate for the particular individual. Even when drugs seem appropriate, it is important to stress that maximal diet therapy should be continued. Several drugs, used singly or in combination, are now available. These include the bile-acid sequestrants (cholestyramine

248 Angina

and colestipol), nicotinic acid, probucol, and the fibric acids (clofibrate and gemfibrozil). Of these, bile-acid sequestrants and nicotinic acid have been shown to reduce coronary heart disease. Clofibrate, while effective in treating one rare familial form of lipid abnormality (Type III hyperlipoproteinemia), is not recommended because it is not effective in most individuals with a high blood cholesterol level but normal triglyceride level. Moreover, an excess overall mortality was reported in the World Health Organization trial of this drug. We still do not have direct evidence for the safety of any cholesterol-lowering drugs when given over decades; therefore, drug treatment should be undertaken cautiously and its desirability should be periodically reevaluated, particularly in children. Individuals with high-risk blood cholesterol (severe hypercholesterolemia), especially those with the hereditary form, may well require drug therapy in addition to dietary modification. Combined drug treatment (e.g., bile-acid sequestrant plus nicotinic acid) may be particularly effective. Several combined treatment regimens are under study. Individuals with moderaterisk blood cholesterol will usually respond adequately to diet alone. Judgment on the decision to use drugs in such patients must be made on a case-by-case basis, taking into account family history of coronary heart disease, existing coronary disease in the individual, coexistence of other risk factors, and age of the individual. Who Should Be Treated? As described above, individuals with high- and moderate-risk cholesterol levels (greater than the 75th percentile) should be treated with diet or diet and drugs. Furthermore, it is clearly recognized that it is a goal to encourage reduction of the blood cholesterol to approximately 180 mg/dl for adults under the age of 30 years and to approximately 200 mg/dl for individuals age 30 or older. This is recognized as a realistic “target” level that should be possible to achieve and that would be predicted to have a beneficial effect on coronary heart disease risk. As will be discussed in the following section, it is recommended that all individuals in the population consume a diet composed of approximately 30 percent of the calories as fat (10 percent or less saturated fat) and 250 to 300 mg of cholesterol a day in an attempt to shift the blood cholesterol levels in our population toward the lower levels observed in populations having much lower rates of coronary heart disease. Both men and women at high risk, as defined above, should be treated similarly, even though premenopausal women have an apparent protection, and the onset of the disease occurs later than in men. However, as in men,

Physical Activity and Cardiovascular Health 249

the leading cause of death in women is coronary heart disease, and blood cholesterol is a risk factor. Despite the fact that direct intervention studies have not been conducted in women, there is no reason to propose a separate treatment schedule for women. Studies are available that indicate a beneficial effect of treating high cholesterol levels in individuals with preexisting clinical disease (secondary intervention) as well as in individuals without preexisting clinical disease (primary intervention). Because of their vulnerability, patients with established disease, including particularly patients with coronary bypass grafts, should be intensively treated. It is encouraging that the progression of established lesions may be retarded by appropriate dietary and drug therapy. The same may apply to the elderly patient. While there is no direct evidence on the benefit to be expected in the elderly, and while blood cholesterol becomes less important as a risk factor in old age, dietary treatment (with due attention to ensure nutritional adequacy) may still be helpful.

Special Guidelines for Management of Children Identifying and treating children with elevated blood cholesterol levels is a subject for special consideration. It is desirable to begin prevention in childhood because patterns of lifestyle are developed in childhood. The moderate-fat and moderate-cholesterol diets recommended for the population at large in this report should be suitable for all family members, including healthy children over the age of 2 years. For children, the diets should provide all nutrients in quantities adequate to assure growth and development and meet energy requirements. Excessive gain in weight should be avoided. The diet may be inappropriate in children or in the elderly if they are malnourished or have special nutritional requirements. For others, the diet plan is safe and nutritionally adequate. Children at “high-risk” should be identified primarily by carefully obtained family histories rather than routine screening. The history should include parents, grandparents, and all first-degree relatives. A family history of hypercholesterolemia or premature coronary heart disease should alert the physician to obtain at least two blood cholesterol determinations. If the blood cholesterol level in such “high-risk” children is above the 75th percentile (approximately 170 mg/dl for ages 2 to 19 years), total and HDL cholesterol should be obtained. Those children with blood cholesterol levels between the 75th and 90th percentile (170 to 185 mg/dl) should be counseled regarding diet and other cardiovascular risk factors and then followed at 1-

250 Angina

year intervals. Those with levels above the 90th percentile (over 185 mg/dl) require special dietary instruction and close supervision with evaluation of other risk factors. A child with a blood cholesterol level above the 95th percentile (greater than 200 mg/dl) on two occasions is in a special category and may have one of the hereditary hypercholesterolemias. Strict dietary intervention is indicated and will be sufficient for many children. Nonresponders should be considered for treatment with a lipid-lowering agent, e.g., bile-acid sequestrant (such as cholestyramine). All family members should be screened. Dietary management of children with elevated blood cholesterol levels should be part of total management that includes regular exercise programs, maintenance of ideal weight, avoidance of excess salt and avoidance of cigarette smoking.

What Screening Strategy Should Be Adopted for Finding Subjects with High Blood Cholesterol? According to data from the National Center for Health Statistics, a high percentage of the American population sees a physician at least once every year. If a cholesterol level were determined on adults at these visits, many of the individuals with cholesterol levels above the 75th percentile would be identified in a relatively short time and should be evaluated and treated as described above. This physician- and clinic-oriented method for screening would be cost-effective. Obviously, some patients may not see a physician for several years, and it would be advisable to educate the public to the importance of knowing one’s cholesterol level. In children, only a “family history screening” is recommended, that is, cholesterol levels should be obtained in those at higher risk because of a strong family history, as discussed above. Educational programs developed by voluntary and public health organizations in conjunction with the National Cholesterol Education Program of the National Heart, Lung, and Blood Institute, as recommended by this consensus panel, should alert all adults to the advisability of learning their cholesterol level. While we are not at this time recommending mass screening, a feasibility study of various screening methods in adults should be considered. Screening necessitates the availability of laboratories capable of determining precisely and accurately the blood cholesterol and HDL cholesterol levels and of physicians willing and able to manage large numbers of new patients. Thus, preliminary steps are needed before mass screening can be considered.

Physical Activity and Cardiovascular Health 251

Reducing the Blood Cholesterol of the General Population Rationale for Recommendations to the General Population Many compelling lines of evidence link blood cholesterol to coronary heart disease. There is also good evidence from epidemiologic studies that the relationship between level of cholesterol and level of risk for coronary heart disease covers virtually the entire cholesterol distribution for the U.S. population. In fact, recent epidemiologic studies suggest that the relationship holds even at the lower end of the spectrum of cholesterol levels found in our population. The Japanese population, in comparison with the U.S. population, is characterized by a much lower average cholesterol level and a much lower frequency of coronary heart disease. The Finnish, on the other hand, have a much higher average cholesterol level and a much greater risk of coronary heart disease than do U.S. citizens. Furthermore, Japanese who have migrated to Hawaii and to San Francisco have higher cholesterol levels and a higher risk of coronary heart disease than nonmigrants. Compilation of all the available data suggests that it will be beneficial to lower the blood cholesterol of the average American. In recent years, Americans have been changing their habitual diet in the direction we recommend, that is, by reducing their intake of total fat, saturated fat, and cholesterol and by increasing intake of polyunsaturated fat. This has been accompanied by a substantial reduction in the average blood cholesterol of the population. In addition, all-cause mortality, cardiovascular mortality, and coronary heart disease mortality have also decreased, but it is difficult to determine with certainty how much, if any, of this decrease is due to changes in diet, blood pressure, cigarette usage, or improved medical care. It is hoped that improved surveillance systems will clarify these issues.

Recommendations In the general population, the basic intervention should be based on diet rather than drugs. We recommend a shift from the current typical American diet to one that is lower in total fat, saturated fat, and cholesterol. Diets with these characteristics are the usual diets consumed in a number of other countries, e.g., Japan and Greece. Life expectancy in these two countries is, at

252 Angina

virtually every age, greater than that in the United States. This applies also to the life expectancy in middle age, when mortality from coronary heart disease begins to rise sharply. The evidence justifies for men, women, and children ages 2 years and older the reduction of calories from fat from the present average level of 40 percent to 30 percent, calories from saturated fat to 10 percent or less, and dietary cholesterol to no more than 250 to 300 mg daily. We recommend that calories from polyunsaturated fat be increased, but not exceed 10 percent of total calories. This diet is generally consistent with the most recent recommendations of the American Heart Association and the Atherosclerosis Study Group of the Inter-Society Commission on Heart Disease Resources. Equally important, individuals, health professionals, and health agencies must recognize the need to control obesity both to aid in controlling blood cholesterol levels and to reduce the other health risks of obesity. Other elements important to the prevention of cardiovascular disease, including avoidance of cigarettes, control of high blood pressure, and maintenance of reasonable levels of physical activity are recommended. Means of Implementing Dietary Recommendations in the General Population ·

If dietary intervention in the general population is to be effective, the eating habits of the entire family must be changed. Thus, the recommended diet should be available to all family members except those under age 2.

·

Educational services that enable adults and children to make informed choices concerning their eating habits should be readily available, including ready availability of data on composition of natural and processed foods.

·

Professional educational programs for physicians, dietitians, and other health professionals should be expanded to include adequate material on diet and heart disease.

·

Specific food items consistent with the recommended diet should be available, accessible, and affordable.

·

The food industry should accelerate its current efforts to develop, produce, and market leaner meats and other foods, including dairy products, with reduced total fat, saturated fat, and cholesterol content.

·

Restaurants, including fast-food outlets, should make foods satisfying these diet recommendations available to their customers.

Physical Activity and Cardiovascular Health 253

·

Government and school food programs should serve meals consistent with these recommendations.

·

Food labeling should include total calories, fat source and total fat, saturated fat, polyunsaturated fat, and cholesterol content as well as other essential nutritional information. If necessary, appropriate statutory or other changes to require such labeling should be seriously considered.

·

A national cholesterol education program should be implemented for physicians, other health professionals (including those in training) and the public; its effectiveness should be periodically evaluated.

Research Directions We know that blood cholesterol is causally related to coronary heart disease and that the atherosclerotic process can be influenced by intervention. However, much about lipid metabolism and about the mechanisms of the atherosclerotic process remains unknown. ·

Cellular and Molecular Biology --A better understanding of lipoprotein production and removal, lipoprotein receptors, and apolipoproteins is needed. More information is needed with regard to factors controlling the level of HDL and its role in preventing coronary heart disease. To learn whether diets very high in polyunsaturated fatty acids have any adverse effects, more information is needed regarding their biochemical and biological effects, including those of the highly unsaturated fatty acids found in fish oils. Research is also needed on the biology of vessel wall injury, on the cells that participate in atherosclerosis, and on the events that trigger thrombosis in atherosclerotic vessels.

·

Clinical Investigation --Precisely defined diets and pharmacologic interventions to reduce blood cholesterol and other lipids must be studied in individuals under carefully controlled conditions. Research on the effectiveness of regimens to lower blood cholesterol and influence atherosclerosis, including surgical intervention, should also be conducted. Evaluation of these may involve atherosclerotic plaque measurement using safe, precise imaging techniques such as ultrasound, regional radioscintigraphy, magnetic resonance, and/or computerenhanced radiography.

·

Pharmacologic Research --New compounds that are more effective, economical, and safe for the reduction of blood cholesterol are needed. Development of improved, more palatable, and less expensive bile-acid sequestrants also is needed. Similarly, a search for pharmacologic agents

254 Angina

that would favorably influence other elements of the atherosclerotic process is highly desirable. ·

Food Product Research --The interface of human nutrition and human disease requires collaborative efforts within the agricultural, industrial, and health research communities. More food products that are high in nutrition quality and taste, yet low in fat and cholesterol, need to be developed.

·

Research in Human Behavior --Study of how people choose their diets and how food habits can be improved is necessary. Studies designed to measure and enhance adherence to new nutritional behaviors and treatment programs are needed.

·

Epidemiologic Investigation --The search for additional factors that initiate or affect the atherosclerotic process must be continued along with further studies of risk factors in major population subgroups, including blacks. As nutritional practices of the population change and as health professionals improve management of elevated blood cholesterol levels, ongoing monitoring of nutritional patterns, blood cholesterol levels, and disease and death outcomes is essential. An important corollary will be monitoring to assess disease incidence, prevalence, and case fatality rates. Research to assess the effects of blood cholesterol reduction on cardiovascular and all-cause mortality is needed. Overall safety of longterm intervention with diet and drugs should be investigated.

·

Secondary Prevention --The effectiveness of lowering blood cholesterol by medical or surgical intervention to retard or reverse atherosclerotic lesions in arteries or bypass grafts of patients with established coronary heart disease requires further investigation.

·

Community Applications --Community demonstration research to test the effectiveness of nutrition-educational programs that influence food choices and other risk-factor behaviors of the healthy free-living population is needed.

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The

Physical Activity and Cardiovascular Health 255

years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH]

256 Angina

Physical Activity and Cardiovascular Health 257

APPENDIX G. PHYSICAL ACTIVITY AND CARDIOVASCULAR HEALTH Overview NIH Consensus Development Conferences are convened to evaluate available scientific information and resolve safety and efficacy issues related to biomedical technology. The resultant NIH Consensus Statements are intended to advance understanding of the technology or issue in question and to be useful to health professionals and the public.61 Each NIH consensus statement is the product of an independent, non-Federal panel of experts and is based on the panel’s assessment of medical knowledge available at the time the statement was written. Therefore, a consensus statement provides a “snapshot in time” of the state of knowledge of the conference topic. The NIH makes the following caveat: “When reading or downloading NIH consensus statements, keep in mind that new knowledge is inevitably accumulating through medical research. Nevertheless, each NIH consensus statement is retained on this website in its original form as a record of the NIH Consensus Development Program.”62 The following concensus statement was posted on the NIH site and not indicated as “out of date” in March 2002. It was originally published, however, in December 1995.63

This paragraph has been adapted from the NIH: http://odp.od.nih.gov/consensus/cons/cons.htm. 62 Adapted from the NIH: http://odp.od.nih.gov/consensus/cons/consdate.htm. 63 Physical Activity and Cardiovascular Health. NIH Consensus Statement Online 1995 December 18-20 [cited 2002 February 19]; 13(3):1-33. http://consensus.nih.gov/cons/101/101_statement.htm. 61

258 Angina

Abstract Objective To provide physicians and the general public with a responsible assessment of the relationship between physical activity and cardiovascular health.

Participants A non-Federal, nonadvocate, 13-member panel representing the fields of cardiology, psychology, exercise physiology, nutrition, pediatrics, public health, and epidemiology. In addition, 27 experts in cardiology, psychology, epidemiology, exercise physiology, geriatrics, nutrition, pediatrics, public health, and sports medicine presented data to the panel and a conference audience of 600.

Evidence The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience.

Consensus Process The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. Conclusions All Americans should engage in regular physical activity at a level appropriate to their capacity, needs, and interest. Children and adults alike should set a goal of accumulating at least 30 minutes of moderate-intensity physical activity on most, and preferably, all days of the week. Most

Physical Activity and Cardiovascular Health 259

Americans have little or no physical activity in their daily lives, and accumulating evidence indicates that physical inactivity is a major risk factor for cardiovascular disease. However, moderate levels of physical activity confer significant health benefits. Even those who currently meet these daily standards may derive additional health and fitness benefits by becoming more physically active or including more vigorous activity. For those with known cardiovascular disease, cardiac rehabilitation programs that combine physical activity with reduction in other risk factors should be more widely used.

Causes and Risk Factors Over the past 25 years, the United States has experienced a steady decline in the age-adjusted death toll from cardiovascular disease (CVD), primarily in mortality caused by coronary heart disease and stroke. Despite this decline, coronary heart disease remains the leading cause of death and stroke the third leading cause of death. Lifestyle improvements by the American public and better control of the risk factors for heart disease and stroke have been major factors in this decline. Coronary heart disease and stroke have many causes. Modifiable risk factors include smoking, high blood pressure, blood lipid levels, obesity, diabetes, and physical inactivity. In contrast to the positive national trends observed with cigarette smoking, high blood pressure, and high blood cholesterol, obesity and physical inactivity in the United States have not improved. Indeed automation and other technologies have contributed greatly to lessening physical activity at work and home. The purpose of this conference was to examine the accumulating evidence on the role of physical activity in the prevention and treatment of CVD and its risk factors. Physical activity in this statement is defined as “bodily movement produced by skeletal muscles that requires energy expenditure” and produces healthy benefits. Exercise, a type of physical activity, is defined as “a planned, structured, and repetitive bodily movement done to improve or maintain one or more components of physical fitness.” Physical inactivity denotes a level of activity less than that needed to maintain good health. Physical inactivity characterizes most Americans. Exertion has been systematically engineered out of most occupations and lifestyles. In 1991, 54

260 Angina

percent of adults reported little or no regular leisure physical activity. Data from the 1990 Youth Risk Behavior Survey show that most teenagers in grades 9-12 are not performing regular vigorous activity. About 50 percent of high school students reported they are not enrolled in physical education classes. Physical activity protects against the development of CVD and also favorably modifies other CVD risk factors, including high blood pressure, blood lipid levels, insulin resistance, and obesity. The type, frequency, and intensity of physical activity that are needed to accomplish these goals remain poorly defined and controversial. Physical activity is also important in the treatment and management of patients with CVD or increased risk, including those who have hypertension, stable angina, a prior myocardial infraction, peripheral vascular disease, or heart failure. Physical activity is an important component of cardiac rehabilitation, and people with CVD may benefit from participation. In addition to potential advantages, questions remain regarding benefits, risks, and costs associated with becoming physically active. Many factors influence adopting and maintaining a physically active lifestyle, such as socioeconomic status, cultural influences, age, and health status. Understanding is needed on how such variables influence the adoption of this behavior at the individual level. Intervention strategies for encouraging individuals from different backgrounds to adopt and adhere to a physically active lifestyle need to be developed and tested. Different environments such as schools, worksites, health care settings, and the home can play a role in promoting physical activity. These community-level factors also need to be better understood. To address these and related issues, the National Heart, Lung, and Blood Institute and the NIH Office of Medical Applications of Research convened a Consensus Development Conference on Physical Activity and Cardiovascular Health. The conference was cosponsored by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Nursing Research, and the Office of Research on Women’s Health and the Office of Disease Prevention of the NIH; the Centers for Disease Control and Prevention; and the President’s Council on Physical Fitness and Sports.

Physical Activity and Cardiovascular Health 261

The conference brought together specialists in medicine, exercise physiology, health behavior, epidemiology, nutrition, physical therapy, and nursing as well as representatives from the public. After 1-1/2 days of presentations and audience discussion, an independent, non-Federal consensus panel weighed the scientific evidence and developed a draft statement that addressed the following five questions. ·

What is the health burden of a sedentary lifestyle on the population?

·

What type, what intensity, and what quantity of physical activity are important to prevent cardiovascular disease?

·

What are the benefits and risks of different types of physical activity for people with cardiovascular disease?

·

What are the successful approaches to adopting and maintaining a physically active lifestyle?

·

What are the important questions for future research?

Sedentary Lifestyle Physical inactivity among the U.S. population is now widespread. National surveillance programs have documented that about one in four adults (more women than men) currently have sedentary lifestyles with no leisure time physical activity. An additional one-third of adults are insufficiently active to achieve health benefits. The prevalence of inactivity varies by gender, age, ethnicity, health status, and geographic region but is common to all demographic groups. Change in physical exertion associated with occupation has declined markedly in this century. Girls become less active than do boys as they grow older. Children become far less active as they move through adolescence. Obesity is increasing among children. It is related to an energy imbalance (i.e., calories consumed in excess of calorie expenditure [physical activity].) Data indicate that obese children and adolescents have a high risk of becoming obese adults, and obesity in adulthood is related to coronary artery disease, hypertension, and diabetes. Thus, the prevention of childhood obesity has the potential of preventing CVD in adults. At age 12, 70 percent of children report participation in vigorous physical activity; by age 21 this activity falls to 42 percent for men and 30 percent for women. Furthermore, as adults age, their physical activity levels continue to decline.

262 Angina

Although knowledge about physical inactivity as a risk factor for CVD has come mainly from investigations of middle-aged, white men, more limited evidence from studies in women minority groups and the elderly suggests that the findings are similar in these groups. On the basis of current knowledge, we must note that physical inactivity occurs disproportionately among Americans who are not well educated and who are socially or economically disadvantaged. Physical activity is directly related to physical fitness. Although the means of measuring physical activity have varied between studies (i.e., there is no standardization of measures), evidence indicates that physical inactivity and lack of physical fitness are directly associated with increased mortality from CVD. The increase in mortality is not entirely explained by the association with elevated blood pressure, smoking, and blood lipid levels. There is an inverse relationship between measures of physical activity and indices of obesity in most U.S. population studies. Only a few studies have examined the relationship between physical activity and body fat distribution, and these suggest an inverse relationship between levels of physical activity and visceral fat. There is evidence that increased physical activity facilitates weight loss and that the addition of physical activity to dietary energy restriction can increase and help to maintain loss of body weight and body fat mass. Middle-aged and older men and women who engage in regular physical activity have significantly higher high-density lipoprotein (HDL) cholesterol levels than do those who are sedentary. When exercise training has extended to at least 12 weeks, beneficial HDL cholesterol level changes have been reported. Most studies of endurance exercise training of individuals with normal blood pressure and those with hypertension have shown decreases in systolic and diastolic blood pressure. Insulin sensitivity is also improved with endurance exercise. A number of factors that affect thrombotic function -- including hematocrit, fibrinogen, platelet function, and fibrinolysis -- are related to the risk of CVD. Regular endurance exercise lowers the risk related to these factors. The burden of CVD rests most heavily on the least active. In addition to its powerful impact on the cardiovascular system, physical inactivity is also associated with other adverse health effects, including osteoporosis, diabetes, and some cancers.

Physical Activity and Cardiovascular Health 263

Prevention Activity that reduces CVD risk factors and confers many other health benefits does not require a structured or vigorous exercise program. The majority of benefits of physical activity can be gained by performing moderate-intensity activities. The amount or type of physical activity needed for health benefits or optimal health is a concern due to limited time and competing activities for most Americans. The amount and types of physical activity that are needed to prevent disease and promote health must, therefore, be clearly communicated, and effective strategies must be developed to promote physical activity to the public. The quantitative relationship between level of activity or fitness and magnitude of cardiovascular benefit may extend across the full range of activity. A moderate level of physical activity confers health benefits. However, physical activity must be performed regularly to maintain these effects. Moderate-intensity activity performed by previously sedentary individuals results in significant improvement in many health-related outcomes. These moderate-intensity activities are more likely to be continued than are high-intensity activities. We recommend that all people in the United States increase their regular physical activity to a level appropriate to their capacities, needs, and interest. We recommend that all children and adults should set a long-term goal to accumulate at least 30 minutes or more of moderate-intensity physical activity on most, or preferably all, days of the week. Intermittent or shorter bouts of activity (at least 10 minutes), including occupational, nonoccupational, or tasks of daily living, also have similar cardiovascular and health benefits if performed at a level of moderate intensity (such as brisk walking, cycling, swimming, home repair, and yardwork) with an accumulated duration of at least 30 minutes per day. People who currently meet the recommended minimal standards may derive additional health and fitness benefits from becoming more physically active or including more vigorous activity. Some evidence suggests lowered mortality with more vigorous activity, but further research is needed to more specifically define safe and effective levels. The most active individuals have lower cardiovascular morbidity and mortality rates than do those who are least active; however, much of the benefit appears to be accounted for by comparing the least active individuals

264 Angina

to those who are moderately active. Further increases in the intensity or amount of activity produce further benefits in some, but not all, parameters of risk. High-intensity activity is also associated with an increased risk of injury, discontinuation of activity, or acute cardiac events during the activity. Current low rates of regular activity in Americans may be partially due to the misperception of many that vigorous, continuous exercise is necessary to reap health benefits. Many people, for example, fail to appreciate walking as “exercise” or to recognize the substantial benefits of short bouts (at least 10 minutes) of moderate-level activity. The frequency, intensity, and duration of activity are interrelated. The number of episodes of activity recommended for health depends on the intensity and/or duration of the activity: higher intensity or longer duration activity could be performed approximately three times weekly and achieve cardiovascular benefits, but low-intensity or shorter duration activities should be performed more often to achieve cardiovascular benefits. The appropriate type of activity is best determined by the individual’s preferences and what will be sustained. Exercise, or a structured program of activity, is a subset of activity that may encourage interest and allow for more vigorous activity. People who perform more formal exercise (i.e., structured or planned exercise programs) can accumulate this daily total through a variety of recreational or sports activities. People who are currently sedentary or minimally active should gradually build up to the recommended goal of 30 minutes of moderate activity daily by adding a few minutes each day until reaching their personal goal to reduce the risk associated with suddenly increasing the amount or intensity of exercise. (The defined levels of effort depend on individual characteristics such as baseline fitness and health status.) Developing muscular strength and joint flexibility is also important for an overall activity program to improve one’s ability to perform tasks and to reduce the potential for injury. Upper extremity and resistance (or strength) training can improve muscular function, and evidence suggests that there may be cardiovascular benefits, especially in older patients or those with underlying CVD, but further research and guidelines are needed. Older people or those who have been deconditioned from recent inactivity or illness may particularly benefit from resistance training due to improved ability in accomplishing tasks of daily living. Resistance training may contribute to better balance, coordination, and agility that may help prevent falls in the elderly.

Physical Activity and Cardiovascular Health 265

Physical activity carries risks as well as benefits. The most common adverse effects of activity relate to musculoskeletal injury and are usually mild and self-limited. The risk of injury increases with increased intensity, frequency, and duration of activity and also depends on the type of activity. Exerciserelated injuries can be reduced by moderating these parameters. A more serious but rare complication of activity is myocardial infraction or sudden cardiac death. Although persons who engage in vigorous physical activity have a slight increase in risk of sudden cardiac death during activity, the health benefits outweigh this risk because of the large overall risk reduction. In children and young adults, exertion-related deaths are uncommon and are generally related to congenital heart defects (e.g., hypertrophic cardiomyopathy, Marfan’s syndrome, severe aortic valve stenosis, prolonged QT syndromes, cardiac conduction abnormalities) or to acquired myocarditis. It is recommended that patients with those conditions remain active but not participate in vigorous or competitive athletics. Because the risks of physical activity are very low compared with the health benefits, most adults do not need medical consultation or pretesting before starting a moderate-intensity physical activity program. However, those with known CVD and men over age 40 and women over age 50 with multiple cardiovascular risk factors who contemplate a program of vigorous activity should have a medical evaluation prior to initiating such a program.

Benefits and Risks of Different Types of Physical Activity More than 10 million Americans are afflicted with clinically significant CVD, including myocardial infraction, angina pectoris, peripheral vascular disease, and congestive heart failure. In addition, more than 300,000 patients per year are currently subjected to coronary artery bypass surgery and a similar number to percutaneous transluminal coronary angioplasty. Increased physical activity appears to benefit each of these groups. Benefits include reduction in cardiovascular mortality, reduction of symptoms, improvement in exercise tolerance and functional capacity, and improvement in psychological well-being and quality of life. Several studies have shown that exercise training programs significantly reduce overall mortality, as well as death caused by myocardial infraction. The reported reductions in mortality have been highest -- approximately 25 percent -- in cardiac rehabilitation programs that have included control of other cardiovascular risk factors. Rehabilitation programs using both

266 Angina

moderate and vigorous physical activity have been associated with reductions in fatal cardiac events, although the minimal or optimal level and duration of exercise required to achieve beneficial effects remain uncertain. Data are inadequate to determine whether stroke incidence is affected by physical activity or exercise training. The risk of death during medically supervised cardiac exercise training programs is very low. However, those who exercise infrequently and have poor functional capacity at baseline may be at somewhat higher risk during exercise training. All patients with CVD should have a medical evaluation prior to participation in a vigorous exercise program. Appropriately prescribed and conducted exercise training programs improve exercise tolerance and physical fitness in patients with coronary heart disease. Moderate as well as vigorous exercise training regimens are of value. Patients with low basal levels of exercise capacity experience the most functional benefits, even at relatively modest levels of physical activity. Patients with angina pectoris typically experience improvement in angina in association with a reduction in effort-induced myocardial ischemia, presumably as a result of decreased myocardial oxygen demand and increased work capacity. Patients with congestive heart failure also appear to show improvement in symptoms, exercise capacity, and functional well-being in response to exercise training, even though left ventricular systolic function appears to be unaffected. The exercise program should be tailored to the needs of these patients and supervised closely in view of the marked predisposition of these patients to ischemic events and arrhythmias. Cardiac rehabilitation exercise training often improves skeletal muscle strength and oxidative capacity and, when combined with appropriate nutritional changes, may result in weight loss. In addition, such training generally results in improvement in measures of psychological status, social adjustment, and functional capacity. However, cardiac rehabilitation exercise training has less influence on rates of return to work than many nonexercise variables, including employer attitudes, prior employment status, and economic incentives. Multifactorial intervention programs -- including nutritional changes and medication plus exercise -- are needed to improve health status and reduce cardiovascular disease risk. Cardiac rehabilitation programs have traditionally been institutional-based and group-centered (e.g., hospitals, clinics, community centers). Referral and enrollment rates have been relatively low, generally ranging from 10 to 25

Physical Activity and Cardiovascular Health 267

percent of patients with CHD. Referral rates are lower for women than for men and lower for non-whites than for whites. Home-based programs have the potential to provide rehabilitative services to a wider population. Homebased programs incorporating limited hospital visits with regular mail or telephone follow-up by a nurse case manager have demonstrated significant increases in functional capacity, smoking cessation, and improvement in blood lipid levels. A range of options exists in cardiac rehabilitation including site, number of visits, monitoring, and other services. There are clear medical and economic reasons for carrying out cardiac rehabilitation programs. Optimal outcomes are achieved when exercise training is combined with educational messages and feedback about changing lifestyle. Patients who participate in cardiac rehabilitation programs show a lower incidence of rehospitalization and lower charges per hospitalization. Cardiac rehabilitation is a cost-efficient therapeutic modality that should be used more frequently.

Successful Approaches The cardiovascular benefits from and physiological reactions to physical activity appear to be similar among diverse population subgroups defined by age, gender, income, region of residence, ethnic background, and health status. However, the behavioral and attitudinal factors that influence the motivation for and ability to sustain physical activity are strongly determined by social experiences, cultural background, and physical disability and health status. For example, perceptions of appropriate physical activity differ by gender, age, weight, marital status, family roles and responsibilities, disability, and social class. Thus, the following general guidelines will need to be further refined when one is planning with or prescribing for specific individuals and population groups, but generally physical activity is more likely to be initiated and maintained if the individual: ·

Perceives a net benefit.

·

Chooses an enjoyable activity.

·

Feels competent doing the activity.

·

Feels safe doing the activity.

·

Can easily access the activity on a regular basis.

·

Can fit the activity into the daily schedule.

268 Angina

·

Feels that the activity does not generate financial or social costs that he or she is unwilling to bear.

·

Experiences a minimum of negative consequences such as injuries, loss of time, negative peer pressure, and problems with self-identity.

·

Is able to successfully address issues of competing time demands.

·

Recognizes the need to balance the use of labor-saving devices (e.g., power lawnmowers, golf carts, automobiles) and sedentary activities (e.g., watching television, use of computers) with activities that involve a higher level of physical exertion.

Other people in the individual’s social environment can influence the adoption and maintenance of physical activity. Health care providers have a key role in promoting smoking cessation and other risk-reduction behaviors. Preliminary evidence suggests that this also applies to physical activity. It is highly probable that people will be more likely to increase their physical activity if their health care provider counsels them to do so. Providers can do this effectively by learning to recognize stages of behavior change, to communicate the need for increased activity, to assist the patient in initiating activity, and by following up appropriately. Family and friends can also be important sources of support for behavior change. For example, spouses or friends can serve as “buddies,” joining in the physical activity; or a spouse could offer to take on a household task, giving his or her mate time to engage in physical activity. Parents can support their children’s activity by providing transportation, praise, and encouragement, and by participating in activities with their children. Worksites have the potential to encourage increased physical activity by offering opportunities, reminders, and rewards for doing so. For example, an appropriate indoor area can be set aside to enable walking during lunch hours. Signs placed near elevators can encourage the use of the stairs instead. Discounts on parking fees can be offered to employees who elect to park in remote lots and walk. Schools are a major community resource for increasing physical activity, particularly given the urgent need to develop strategies that affect children and adolescents. As noted previously, there is now clear evidence that U.S. children and adolescents have become more obese. There is also evidence that obese children and adolescents exercise less than their leaner peers. All schools should provide opportunities for physical activities that:

Physical Activity and Cardiovascular Health 269

·

Are appropriate and enjoyable for children of all skill levels and are not limited to competitive sports or physical education classes.

·

Appeal to girls as well as to boys and youngsters from diverse backgrounds.

·

Can serve as a foundation for activities throughout life.

·

Are offered on a daily basis.

Successful approaches may involve mass education strategies or changes in institutional policies or community variables. In some environments (e.g., schools, worksites, community centers), policy-level interventions may be necessary to enable people to achieve and maintain an adequate level of activity. Policy changes that increase opportunities for physical activity can facilitate activity maintenance for motivated individuals and increase readiness to change among the less motivated. As in other areas of health promotion, mass communication strategies should be used to promote physical activity. These strategies should include a variety of mainstream channels and techniques to reach diverse audiences that acquire information through different media (e.g., TV, newspaper, radio, Internet).

Future Research While much has been learned about the role of physical activity in cardiovascular health, there are many unanswered questions. ·

Maintain surveillance of physical activity levels in the U.S. population by age, gender, geographic, and socioeconomic measures.

·

Develop better methods for analysis and quantification of activity. These methods should be applicable to both work and leisure time measurements and provide direct quantitative estimates of activity.

·

Conduct physiologic, biochemical, and genetic research necessary to define the mechanisms by which activity affects CVD including changes in metabolism as well as cardiac and vascular effects. This will provide new insights into cardiovascular biology that may have broader implications than for other clinical outcomes.

·

Examine the effects of physical activity and cardiac rehabilitation programs on morbidity and mortality in elderly individuals.

·

Conduct research on the social and psychological factors that influence adoption of a more active lifestyle and the maintenance of that behavior change throughout life.

270 Angina

·

Carry out controlled randomized clinical trials among children and adolescents to test the effects of increased physical activity on CVD risk factor levels including obesity. The effects of intensity, frequency, and duration of increased physical activity should be examined in such studies.

Conclusions Accumulating scientific evidence indicates that physical inactivity is a major risk factor for CVD. Moderate levels of regular physical activity confer significant health benefits. Unfortunately, most Americans have little or no physical activity in their daily lives. All Americans should engage in regular physical activity at a level appropriate to their capacities, needs, and interests. All children and adults should set and reach a goal of accumulating at least 30 minutes of moderateintensity physical activity on most, and preferably all, days of the week. Those who currently meet these standards may derive additional health and fitness benefits by becoming more physically active or including more vigorous activity. Cardiac rehabilitation programs that combine physical activity with reduction in other risk factors should be more widely applied to those with known CVD. Well-designed rehabilitation programs have benefits that are lost because of these programs’ limited use. Individuals with CVD and men over 40 or women over 50 years of age with multiple cardiovascular risk factors should have a medical evaluation prior to embarking on a vigorous exercise program. Recognizing the importance of individual and societal factors in initiating and sustaining regular physical activity, the panel recommends the following: ·

Development of programs for health care providers to communicate to patients the importance of regular physical activity.

·

Increased community support of regular physical activity with environmental and policy changes at schools, worksites, community centers, and other sites.

·

Initiation of a coordinated national campaign involving a consortium of collaborating health organizations to encourage regular physical activity.

Physical Activity and Cardiovascular Health 271

The implementation of the recommendations in this statement has considerable potential to improve the health and well-being of American citizens.

Online Glossaries 273

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

·

Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to angina and keep them on file. The NIH, in particular, suggests that patients with angina visit the following Web sites in the ADAM Medical Encyclopedia:

274 Angina

·

Basic Guidelines for Angina Angina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001107.htm

·

Signs & Symptoms for Angina Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Pain in the chest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

·

Diagnostics and Tests for Angina Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm

Online Glossaries 275

Coronary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003875.htm Coronary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003876.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Stress test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003878.htm ·

Surgery and Procedures for Angina Angioplasty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002953.htm

·

Background Topics for Angina Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm

·

Basic Guidelines for Angina

276 Angina

Angina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001107.htm ·

Signs & Symptoms for Angina Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Pain in the chest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

·

Diagnostics and Tests for Angina Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm Coronary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003875.htm

Online Glossaries 277

Coronary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003876.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Stress test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003878.htm ·

Surgery and Procedures for Angina Angioplasty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002953.htm

·

Background Topics for Angina Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

278 Angina

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

·

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

Glossary 279

ANGINA GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse: Harmful. [EU] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

280 Angina

Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH] Alkalosis: A pathologic condition resulting from accumulation of base, or from loss of acid without comparable loss of base in the body fluids, and characterized by decrease in hydrogen ion concentration (increase in pH). [EU]

Amyl Nitrite: A vasodilator that is administered by inhalation. It is also used recreationally due to its supposed ability to induce euphoria and act as an aphrodisiac. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Anesthesiology: A specialty concerned with the study of anesthetics and anesthesia. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. The chief signs of arterial aneurysm are the formation of a pulsating tumour, and often a bruit (aneurysmal bruit) heard over the swelling. Sometimes there are symptoms from pressure on contiguous parts. [EU]

Angina: Chest pain that originates in the heart. [NIH] Angiocardiography: Radiography of the heart and great vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH]

Glossary 281

Antianginal: Counteracting angina or anginal conditions. [EU] Antibiotic: A drug that kills or inhibits the growth of bacteria. [NIH] Antibodies: Specific proteins produced by the body's immune system that bind with foreign proteins (antigens). [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Aorta: Blood vessel that delivers oxygen-rich blood from the left ventricle to the body; it is the largest blood vessel in the body. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Arginine: An essential amino acid that is physiologically active in the Lform. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriography: Roentgenography of arteries after injection of radiopacque material into the blood stream. [EU] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]

Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Showing or causing no symptoms. [EU] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH]

Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH]

Atrial: Pertaining to an atrium. [EU]

282 Angina

Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autonomic: Self-controlling; functionally independent. [EU] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Betablocker: A drug that induces adrenergic blockade at either ß1- or ß2adrenergic receptors or at both. [EU] Bilateral: Having two sides, or pertaining to both sides. [EU] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Bretylium Tosylate: An agent that blocks the release of adrenergic transmitters and may have other actions. It was formerly used as an antihypertensive agent, but is now proposed as an anti-arrhythmic. [NIH] Bronchitis: Inflammation of one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrates: A nutrient that supplies 4 calories/gram. They may be simple or complex. Simple carbohydrates are called sugars, and complex carbohydrates are called starch and fiber (cellulose). An organic

Glossary 283

compound—containing carbon, hydrogen, and oxygen—that is formed by photosynthesis in plants. Carbohydrates are heat producing and are classified as monosaccharides, disaccharides, or polysaccharides. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A disease of the heart muscle (myocardium). [NIH] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catheter: Thin, flexible medical tube; one use is to insert it into a blood vessel to measure blood pressure. [NIH] Catheterization: The employment or passage of a catheter. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU]

Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] CHD: Coronary heart disease. A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU]

284 Angina

Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Chlamydia: A genus of the family chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is chlamydia trachomatis. [NIH] Cholesterol: A soft, waxy substance manufactured by the body and used in the production of hormones, bile acid, and vitamin D and present in all parts of the body, including the nervous system, muscle, skin, liver, intestines, and heart. Blood cholesterol circulates in the bloodstream. Dietary cholesterol is found in foods of animal origin. [NIH] Chronic: Of long duration; frequently recurring. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clostridium: A genus of motile or nonmotile gram-positive bacteria of the family bacillaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Coagulation: 1. the process of clot formation. 2. in colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. in surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [NIH]

Glossary 285

Colitis: Inflammation of the colon. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Criterion: A standard by which something may be judged. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dexfenfluramine: A serotonin agonist drug used to treat obesity. FDA approval has been withdrawn. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU]

Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Dorsal: 1. pertaining to the back or to any dorsum. 2. denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and

286 Angina

low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of lowdensity lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysplasia: Abnormal development or growth. [NIH] Dyspnea: Shortness of breath; difficult or labored breathing. [NIH] Dyspnoea: Difficult or laboured breathing. [EU] ECG: Measurement of electrical activity during heartbeats. [NIH] Echocardiography: A test that bounces sound waves off the heart to produce pictures of its internal structures. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Abnormal fluid accumulation in body tissues. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrocardiogram:

Measurement of electrical activity during heartbeats.

[NIH]

Electrocardiography: The making of graphic records of the variations in electrical potential caused by electrical activity of the heart muscle and detected at the body surface, as a method for studying the action of the heart muscle. [EU] Embolism: A sudden blocking of an artery by an embolus (clot or a foreign material such as a fat globule) brought to the site by the blood flow. [NIH] Emphysema: Chronic lung disease in which there is permanent destruction of alveoli. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels, and the serous cavities of the body, originating from the mesoderm. [EU] Enzyme: Substance, made by living cells, that causes specific chemical changes. [NIH]

Glossary 287

Ephedrine: A sympathomimetic drug that stimulates thermogenesis in laboratory animals and humans. Animal studies show that it may reduce fat content and, therefore, body weight by mechanisms that probably involve increased expenditure and reduced food intake. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epigastric: Pertaining to the epigastrium. [EU] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: A name applied to redness of the skin produced by congestion of the capillaries, which may result from a variety of causes, the etiology or a specific type of lesion often being indicated by a modifying term. [EU] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Fatal: Causing death, deadly; mortal; lethal. [EU] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Felodipine: A dihydropyridine calcium antagonist with positive inotropic

288 Angina

effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] Fenfluramine: A serotonin agonist drug used in the treatment of obesity. FDA approval has been withdrawn. [NIH] Fetus: Unborn offspring from 7 or 8 weeks after conception until birth. [NIH] Fibrinogen: A plasma protein that is converted into fibrin by thrombin in the presence of calcium ions. Fibrin is responsible for the semisolid character of a blood clot. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate

Glossary 289

and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] HDL: Lipoproteins (high-density lipoproteins) that contain a small amount of cholesterol and carry cholesterol away from body cells and tissues to the liver for excretion from the body. Low-level HDL increases the risk of heart disease, so the higher the HDL level, the better. The HDL component normally contains 20 to 30 percent of total cholesterol, and HDL levels are inversely correlated with coronary heart disease risk. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Hirudin: The active principle in the buccal gland secretion of leeches. It acts as an antithrombin and as an antithrombotic agent. [NIH] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those

290 Angina

substances that are not produced by the endocrine glands but that have similar effects. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH]

Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU] Hypertension: High blood pressure (i.e., abnormally high blood pressure tension involving systolic and/or diastolic levels). The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or taking hypertensive medication. The cause may be adrenal, benign, essential, Goldblatt's, idiopathic, malignant PATE, portal, postpartum, primary, pulmonary, renal or renovascular. [NIH] Hypertriglyceridemia: An excess of triglycerides in the blood that is an autosomal dominant disorder with the phenotype of hyperlipoproteinemia, type IV. The National Cholesterol Education Program defines a high level of triglycerides as being between 400 and 1,000 mg/dL. [NIH] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Hyperventilation: A state in which there is an increased amount of air entering the pulmonary alveoli (increased alveolar ventilation), resulting in reduction of carbon dioxide tension and eventually leading to alkalosis. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of

Glossary 291

thyrotropin secretion it is called secondary hypothyroidism. [EU] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH] Immunization: Protection from disease by administering vaccines that induce the body to form antibodies against infectious agents. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Infusion: The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intravenous: Within a vein or veins. [EU] Intubation: Insertion of a tube into an organ in the body. [NIH] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that

292 Angina

acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Kinetic: Pertaining to or producing motion. [EU] LDL: Low-density lipoprotein. Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lipodystrophy: 1. any disturbance of fat metabolism. 2. a group of conditions due to defective metabolism of fat, resulting in the absence of subcutaneous fat, which may be congenital or acquired and partial or total. Called also lipoatrophy and lipodystrophia. [EU] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipoprotein: Protein-coated packages that carry fat and cholesterol throughout the bloodstream. There are four general classes: high-density, low-density, very low-density, and chylomicrons. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the FACE constituting the lower jaw. It supports the lower teeth. [NIH] Mediastinitis: Inflammation of the mediastinum, the area between the pleural sacs. [NIH] Mediator: An object or substance by which something is mediated, such as

Glossary 293

(1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] Menopause: The cessation of menstruation in the human female, which begins at about the age of 50. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] Microcirculation: The flow of blood in the entire system of finer vessels (100 microns or less in diameter) of the body (the microvasculature). [EU] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] MMPI: A personality inventory consisting of statements to be asserted or denied by the individual. The patterns of response are characteristic of certain personality attributes. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monotherapy: A therapy which uses only one drug. [EU] Motility: The ability to move spontaneously. [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the HEART composed of striated, involuntary muscle known as cardiac muscle. [NIH]

294 Angina

Nadolol: A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for migraine and for tremor. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Nasal: Pertaining to the nose. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Neuralgia: Paroxysmal pain which extends along the course of one or more nerves. Many varieties of neuralgia are distinguished according to the part affected or to the cause, as brachial, facial, occipital, supraorbital, etc., or anaemic, diabetic, gouty, malarial, syphilitic, etc. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] NHANES: National Health and Nutrition Examination Survey; conducted every 10 years by the National Center for Health Statistics to survey the dietary habits and health of U.S. residents. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicorandil: A derivative of the niacinamide that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate

Glossary 295

cyclase. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Ocular: 1. of, pertaining to, or affecting the eye. 2. eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Paediatric: Of or relating to the care and medical treatment of children;

296 Angina

belonging to or concerned with paediatrics. [EU] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pemphigus: A group of chronic, relapsing, sometimes fatal skin diseases characterized clinically by the development of successive crops of vesicles and bullae, histologically by acantholysis, and immunologically by serum autoantibodies directed against antigens in the intracellular zones of the epidermis. The specific disease is usually indicated by a modifying term; but the term pemphigus is often used alone to designate pemphigus vulgaris. [EU] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Pericarditis: Inflammation of the pericardium. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the

Glossary 297

treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [NIH]

Physiologic: Normal; not pathologic; characteristic of or conforming to the normal functioning or state of the body or a tissue or organ; physiological. [EU]

Plasminogen: The inactive precursor of plasmin (=enzyme that catalyses the hydrolysis of peptide bonds at the carbonyl end of lysine or arginine residues). [EU] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Postmenopausal: Occurring after the menopause. [EU] Postmenopause: The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life. Since in the United States the age of the menopause ranges between 48 and 55 years, generally conceived as middle age, the postmenopause often refers to women considerably older. [NIH]

Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Precordial: Pertaining to the precordium (= region over the heart and lower part of the thorax). [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prevalence: The number of events, e.g., instances of a given disease or other condition, in a given population at a designated time. When used without qualification, the term usually refers to the situation at specific point in time (point prevalence). Prevalence is a number, not a rate. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progressive: Increasing in severity. [NIH] Propafenone:

An antiarrhythmia agent that is particularly effective in

298 Angina

ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiography: The making of film records (radiographs) of internal structures of the body by passage of x-rays or gamma rays through the body to act on specially sensitized film. [EU] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH]

Randomization: Also called random allocation. Is allocation of individuals

Glossary 299

to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reflux: A backward or return flow. [EU] Refractory: Not readily yielding to treatment. [EU] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiratory: Pertaining to respiration. [EU] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its

300 Angina

principal forms in tissues and cells are as FMN and FAD. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Sedentary: 1. sitting habitually; of inactive habits. 2. pertaining to a sitting posture. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Solvent: 1. dissolving; effecting a solution. 2. a liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU]

Glossary 301

Stabilization: The creation of a stable state. [EU] Standardize: To compare with or conform to a standard; to establish standards. [EU] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Sublingual: Located beneath the tongue. [EU] Surgical: Of, pertaining to, or correctable by surgery. [EU] Syncope: Fainting; temporary loss of consciousness. [NIH] Systemic: Relating to a process that affects the body generally; in this instance, the way in which blood is supplied through the aorta to all body organs except the lungs. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachyarrhythmia: Tachycardia associated with an irregularity in the normal heart rhythm. [EU] Tachycardia: Excessive rapidity in the action of the heart; the term is usually applied to a heart rate above 100 per minute and may be qualified as atrial, junctional (nodal), or ventricular, and as paroxysmal. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Thoracic: Pertaining to or affecting the chest. [EU] Thoracotomy: Surgical incision into the chest wall. [NIH] Thrombolytic: 1. dissolving or splitting up a thrombus. 2. a thrombolytic agent. [EU] Thrombosis: The formation, development, or presence of a thrombus. [EU] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate

302 Angina

thrombus formation from simple coagulation or clot formation. [EU] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

Toothache: Pain in the adjacent areas of the teeth. [NIH] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trismus: Motor disturbance of the trigeminal nerve, especially spasm of the masticatory muscles , with difficulty in opening the mouth; a characteristic early symptom of tetanus. Called also lockjaw. [EU] Trustees: Board members of an institution or organization who are entrusted with the administering of funds and the directing of policy. [NIH] Ulcer: A local defect, or excavation, of the surface of an organ or tissue; which is produced by the sloughing of inflammatory necrotic tissue. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasomotor: 1. affecting the calibre of a vessel, especially of a blood vessel. 2. any element or agent that effects the calibre of a blood vessel. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

Glossary 303

Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] VLDL: Very low-density lipoprotein. The lipoprotein particles that initially leave the liver, carrying cholesterol and lipid. VLDLs contain 10 to 15 percent of the total serum cholesterol along with most of the triglycerides in the fasting serum; VLDLs are precursors of LDL, and some forms of VLDL, particularly VLDL remnants, appear to be atherogenic. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] Xanthomatosis: A condition of morphologic change in which there is accumulation of lipids in the large foam cells of tissues. It is the cutaneous manifestation of lipidosis in which plasma fatty acids and lipoproteins are quantitatively changed. The xanthomatous eruptions have several different distinct morphologies dependent upon the specific form taken by the disease. [NIH]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

304 Angina

·

Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna

·

A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

·

Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

·

Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

·

Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

·

Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna

·

Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

·

Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

·

Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

Index 305

INDEX A Abdomen .................26, 84, 289, 294, 301 Acetylcholine .........................75, 194, 294 Adenosine......................................71, 279 Adjuvant...............................................167 Adolescence ................255, 261, 279, 296 Adrenergic ..76, 83, 84, 92, 149, 150, 280, 281, 282, 294, 296, 298 Adverse ....60, 82, 90, 149, 253, 262, 265, 284 Aerosol ............................................64, 84 Albuterol ......................................149, 280 Alkalosis ........................................74, 290 Anaesthesia...................................74, 291 Anemia ..................................73, 125, 289 Anesthesia.....................................71, 280 Aneurysm ....................................106, 280 Angiocardiography...............................105 Angioplasty .14, 39, 86, 96, 157, 195, 224, 265 Antianginal.............................85, 157, 158 Antibiotic ....................57, 72, 77, 282, 300 Antibodies....................................129, 291 Antihypertensive ....................83, 149, 282 Anxiety...........................................76, 298 Aorta ......................................77, 243, 301 Apolipoproteins...214, 230, 233, 234, 253, 288 Arginine .........................49, 166, 194, 297 Arterial ..13, 26, 77, 82, 90, 105, 106, 222, 242, 280, 295, 301 Arteries .13, 14, 25, 26, 47, 56, 75, 84, 88, 105, 195, 214, 223, 225, 238, 241, 242, 243, 254, 281, 283, 285, 292, 294 Arteriography .........................................41 Assay...................................................226 Asymptomatic ..............................214, 296 Atherogenic 215, 219, 221, 223, 226, 228, 233, 234, 303 Atrial ........................................64, 77, 301 Atropine ...............................................194 Atypical ........................149, 150, 284, 300 Autonomic......................48, 204, 279, 295 B Bacteria ......24, 72, 77, 78, 188, 281, 284, 300, 302 Benign ...........................................48, 290 Bile.........25, 230, 247, 248, 250, 253, 284 Bioavailability.........................................87 Biochemical .................................253, 269 Bleomycin ..............................72, 162, 282

Blister .................................................... 85 Bronchitis ............................................ 104 Buccal ....... 74, 87, 92, 282, 289, 292, 301 C Capsules ................................. 84, 87, 191 Carbohydrates ............ 188, 204, 229, 282 Cardiac. 39, 40, 56, 57, 58, 60, 61, 75, 81, 82, 84, 90, 107, 108, 149, 157, 204, 259, 260, 264, 265, 266, 267, 269, 285, 286, 293, 299 Cardiology............................. 64, 110, 258 Cardiomyopathy.................................. 265 Catabolism .......................................... 222 Catheter ............................ 13, 14, 72, 283 Causal. 218, 220, 224, 234, 239, 241, 243 Causality ............................................. 234 Cerebral .................................. 82, 90, 103 Cervical ................................................. 86 Chemotherapy ........................ 70, 78, 303 Chronic... 22, 54, 55, 65, 67, 87, 101, 103, 108, 161, 164, 214, 219, 227, 235, 296 Chylomicrons ........................ 74, 231, 292 Cisplatin .......................... 70, 72, 162, 284 Coagulation.. 78, 214, 221, 223, 231, 289, 302 Colestipol ............................................ 248 Concomitant.................... 82, 90, 219, 227 Conduction.......................................... 265 Coronary Angiography.............. 60, 61, 96 Criterion .............................................. 245 D Degenerative ...................... 108, 189, 299 Dexfenfluramine.................................. 115 Diarrhea .............................................. 188 Diastolic .................... 48, 82, 90, 262, 290 Diltiazem ....................................... 65, 165 Disposition ............................................ 60 Dobutamine......................................... 194 Dysplasia ............................................ 125 E Echocardiography............................... 194 Edema............................................. 82, 90 Efficacy .. 39, 42, 48, 59, 67, 88, 100, 164, 194, 217, 225, 230, 237, 244, 257, 286 Electrocardiogram....... 13, 15, 54, 55, 102 Emphysema ........................................ 104 Endocarditis ........................................ 104 Endothelium ........................................ 166 Enzyme .. 15, 49, 204, 205, 288, 296, 297, 298

306 Angina

Epidemiological ...................................226 Estrogens ............................................230 Ethanol ..................................................84 Etoposide.............................................162 Extremity..............................................264 F Facial ...........................................108, 294 Fatal......60, 108, 224, 238, 243, 244, 266, 296 Fatigue.........................................255, 281 Fenfluramine........................................115 Fibrinogen..............................55, 102, 262 Fibrinolysis...................................231, 262 Fibrinolytic ...................................223, 234 Flushing .................................................82 G Gastrointestinal..............92, 107, 287, 288 Gemfibrozil ..........................225, 230, 248 Ginseng ...............................................159 Glucose ...................21, 25, 222, 288, 291 Glycerol .................................................84 Groin ................................................13, 14 H Habitual ...............................................251 Hematocrit .............................73, 262, 289 Hemostasis..........................................234 Heparin ..................................59, 100, 167 Heredity .......................................104, 105 Herpes .............................71, 73, 279, 289 Hormones 25, 76, 204, 227, 284, 287, 299 Hydrophilic.......................................84, 85 Hygienic ......218, 219, 220, 230, 231, 232, 233, 234 Hypercholesterolemia.107, 231, 242, 243, 245, 246, 248, 249, 285 Hyperlipidemia....103, 107, 219, 223, 230, 231, 285 Hyperlipoproteinemia...........214, 248, 290 Hypersensitivity ...........................106, 280 Hypertriglyceridemia...107, 218, 219, 223, 228, 230, 231, 232, 233, 285 Hypertrophy .....................................82, 90 Hyperventilation...................................163 Hypothyroidism....................236, 246, 290 I Imipramine.............................................39 Implantation .........................................163 Impotence....................................150, 297 Induction ........................................26, 298 Infarction.....22, 41, 54, 55, 56, 59, 60, 63, 76, 77, 82, 88, 89, 90, 99, 100, 102, 103, 111, 157, 158, 164, 195, 204, 285, 298, 299 Insulin ................25, 82, 96, 260, 288, 291 Intravenous............................................87 Invasive .........................................41, 157

Ischemia..... 13, 39, 40, 60, 77, 81, 82, 88, 90, 110, 111, 158, 167, 193, 266, 299 Isosorbide ........................... 100, 158, 165 L Lesion ................................. 107, 225, 287 Lipophilic ............................................... 85 Lipoprotein ..... 26, 55, 107, 215, 218, 219, 222, 223, 224, 225, 229, 232, 233, 238, 239, 241, 253, 262, 285, 292, 303 M Mammary .............................................. 14 Mandible ....................................... 93, 299 Menopause ............. 49, 76, 102, 297, 298 Molecular . 73, 76, 78, 100, 119, 122, 123, 220, 241, 289, 299, 302 Monotherapy ................................. 64, 165 Motility................................................. 102 Mucosa ................... 85, 92, 292, 293, 301 Myocarditis.......................................... 265 Myocardium ...... 47, 56, 84, 255, 283, 293 N Naloxone......................................... 64, 68 Nasal............................................. 84, 292 Nausea.................................................. 12 Nephrotic..................................... 219, 246 Neuralgia..................................... 108, 294 Neurons ...................................... 150, 295 Neurotransmitter ...... 48, 71, 75, 204, 279, 294, 295 Niacin .......................................... 189, 230 Nicorandil ............................................ 164 Nifedipine .............................. 75, 165, 295 Nitrates........................ 56, 63, 87, 99, 101 Nitroglycerin ...................... 14, 84, 85, 100 Nociceptors ................................... 75, 295 Norepinephrine ............... 75, 91, 279, 294 O Ointments.............................................. 87 Osteoporosis....................................... 262 Overweight.......................... 115, 228, 247 P Pancreatitis ......................... 227, 231, 232 Pathogenesis ...................................... 220 Pediatrics ............................................ 258 Pemphigus .................................. 108, 296 Percutaneous........................ 39, 157, 265 Perfusion................................. 86, 88, 194 Peroxidase .......................................... 195 Pharmacologic .. 39, 71, 96, 227, 253, 280 Pharmacotherapy ............................... 159 Physiologic...................... 76, 93, 269, 299 Plasminogen ......................................... 41 Postmenopausal ..... 41, 57, 226, 230, 232 Postmenopause ............................ 49, 297 Postprandial ........................................ 231 Potassium ............................. 75, 190, 294

Index 307

Precordial ........................................84, 91 Predisposition ......................................266 Prevalence.54, 55, 86, 103, 254, 261, 297 Progesterone .......................................234 Progressive..................................238, 242 Propranolol ..........................................165 Psychology ..........................................258 R Radioactivity ..........................................13 Radiography ........................................253 Randomization.....................................225 Receptor ..............................149, 242, 284 Recurrence ..........................................227 Reflux ..................................................102 Refractory ..........65, 67, 69, 162, 218, 232 Reperfusion ...................................77, 299 Resorption .............................................84 Respiratory ............................57, 106, 280 Riboflavin.............................................188 S Secretion ..74, 75, 77, 236, 289, 291, 293, 300 Sedentary ....227, 261, 262, 263, 264, 268 Seizures.......................................108, 300 Selenium......................................190, 195 Serum .......26, 55, 77, 108, 214, 215, 219, 227, 241, 288, 292, 296, 300, 303 Solvent...................................92, 287, 289 Species ....................72, 77, 242, 284, 300 Spectrum .............................................251 Stabilization .........................................225 Standardize .........................................240 Stenosis ...............................................265 Stomach ..............................107, 164, 288 Sublingual........................................84, 87 Surgical.......42, 69, 77, 86, 111, 241, 253, 254, 299

Sympathetic ...... 48, 49, 91, 204, 279, 295 Systemic ......... 56, 87, 106, 165, 280, 301 Systolic 48, 55, 82, 90, 158, 262, 266, 290 T Tachycardia .......................... 70, 204, 285 Testicular ............................................ 162 Thermoregulation................................ 188 Thoracic .......................................... 70, 86 Thoracotomy......................................... 65 Thrombolytic ........................... 41, 49, 301 Thrombosis ... 26, 103, 231, 233, 253, 301 Thrombus........................ 49, 78, 301, 302 Tolerance 87, 88, 158, 166, 265, 266, 302 Topical ...................... 87, 92, 93, 287, 302 Toxicity................................................ 224 Toxin ............................................. 65, 302 Transcutaneous .. 64, 66, 68, 71, 164, 165 Transdermal.......................................... 87 Triage.............................................. 58, 60 Triglyceride 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 246, 248, 284, 290 U Ulcer................................ 72, 75, 283, 293 V Vascular ... 11, 25, 56, 78, 82, 88, 91, 103, 106, 149, 150, 224, 225, 227, 234, 235, 260, 265, 269, 280, 285, 288, 297, 301 Vasoactive ............................................ 57 Vein......................... 13, 14, 106, 280, 291 Venous...................... 26, 56, 75, 294, 295 Verapamil...................................... 80, 165 Vertigo............................. 75, 78, 295, 303 Vindesine ............................................ 162 Viral....................................................... 59