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46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page i

Epidemiology and
Prevention of
Cardiovascular
Diseases: A Global
ChaLLEnge
second edition

Darwin R. Labarthe, MD, MPH, PhD

46394_FM_00i_xviii.qxd 3/5/10 2:23 PM Page ii

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person should be sought.

This book was written by Darwin R. Labarthe in his private capacity. No official support or endorsement by the Centers for
Disease Control and Prevention, Department of Health and Human Services is intended, nor should be inferred.

Production Credits
Publisher: Michael Brown
Editorial Assistant: Catie Heverling
Editorial Assistant: Teresa Reilly
Production Manager: Tracey Chapman
Senior Marketing Manager: Sophie Fleck
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Composition: Auburn Associates, Inc.
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Printing and Binding: Courier Stoughton
Cover Printing: Courier Stoughton

Library of Congress Cataloging-in-Publication Data

Labarthe, Darwin.
Epidemiology and prevention of cardiovascular diseases : a global challenge / Darwin Labarthe. — 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN-13: 978-0-7637-4689-6 (pbk.)
ISBN-10: 0-7637-4689-4 (pbk.)
1. Cardiovascular system—Diseases—Prevention. 2. Cardiovascular system—Diseases—Epidemiology.
3. Cardiovascular system—Diseases—Etiology. I. Title.
[DNLM: 1. Cardiovascular Diseases—epidemiology. 2. Cardiovascular Diseases—prevention & control.
WG 120 L113e 2011]
RA645.C34L33 2011
614.5'91—dc22
2009044199

6048
Printed in the United States of America
14 13 12 11 10 10 9 8 7 6 5 4 3 2 1
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page iii

Contents

Foreword xi
Preface xiii
Dedication xv
Acknowledgments xvii

PART I—A PUBLIC HEALTH PERSPECTIVE 1

Chapter 1 Cardiovascular Diseases: A Global Public Health Challenge 3

Summary 3
The Epidemiology and Prevention of Cardiovascular Diseases: Definition and Scope 3
The Basis of Public Health Concern Worldwide 5
Rates of Occurrence in Selected Populations and Changes in Recent Decades 10
Current Burdens of Major Cardiovascular Diseases in the United States and the World 12
Opportunities for Prevention 15
References 17

Chapter 2 Distributions and Disparities 19

Summary 19
Introduction 19
Age and Life Stages 22
Sex or Gender 26
Race or Ethnicity 27
Geography or Place 29
Person, Place, and Time 32
Conclusion 35
References 36

iii
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iv CONTENTS

PART II—THE MAJOR CARDIOVASCULAR DISEASES 39

Chapter 3 Atherosclerosis 41

Summary 41
Introduction 41
Methods of Measurement––Invasive and Noninvasive 42
Manifestations––Above and Below the “Clinical Horizon” 43
Mechanisms of Atherogenesis 46
Person, Place, and Time 47
Atherosclerosis in Childhood, Youth, and Early Adulthood 49
Prevention and Treatment of Atherosclerosis 54
Current Issues 55
References 55

Chapter 4 Coronary Heart Disease 59

Summary 59
Introduction 59
Background 62
Population Studies––Definition and Classification, Diagnostic Algorithms, and Criteria 63
Rates 65
Risks 74
Trends and Explanations 79
Forecasts 83
Current Issues 83
References 83
Appendix 4-A: Key to Population Abbreviations Used by the WHO MONICA Project 87

Chapter 5 Stroke 89

Summary 89
Introduction 89
Background 91
Population Studies––Definition, Classification, and Diagnostic Methods 92
Rates 93
Risks 101
Trends 104
Forecasts 107
Current Issues 107
References 107
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page v

CONTENTS v

Chapter 6 Related Conditions 111

Summary 111
Introduction 111
Peripheral Arterial Disease 113
Aortic Aneurysm 120
Chronic Heart Failure 123
Deep Vein Thrombosis and Pulmonary Embolism 132
Arrhythmias 135
References 136

PART III—THE MAIN DETERMINANTS 139

Chapter 7 Genes and Environment 141

Summary 141
Introduction 142
Concepts and Strategies of Genetic Epidemiology 144
Family History 146
Gene–Environment Interaction 150
Cardiovascular Applications of Genomic Epidemiology 152
Current Issues 155
References 156

Chapter 8 Dietary Imbalance 159

Summary 159
Introduction 159
Concepts and Definitions of Dietary Patterns 161
Measurement 165
Determinants 168
Distribution 170
Cardiovascular-Related Effects of Diet 172
Prevention and Control 180
Current Issues 185
References 186

Chapter 9 Physical Inactivity 191

Summary 191
Introduction 191
Concepts and Definitions 192
Measurement 194
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page vi

vi CONTENTS

Determinants 194
Mechanisms 196
Distribution 197
Cardiovascular-Related Effects 204
Prevention and Control 211
Current Issues 217
References 218

Chapter 10 Obesity 223

Summary 223
Introduction 224
Concepts and Definitions 224
Measurement 229
Determinants 229
Mechanisms 233
Distribution 236
Rates and Risks 244
Prevention and Control 253
Current Issues 262
References 262

Chapter 11 Adverse Blood Lipid Profile 269

Summary 269
Introduction 269
Concepts and Definitions 270
Measurement 273
Determinants 274
Mechanisms 275
Distribution 277
Relation to Rates and Risks 283
Relation to Other Factors 290
Prevention and Control 292
Current Issues 302
References 304

Chapter 12 High Blood Pressure 311

Summary 311
Introduction 312
Concepts and Definitions 312
Measurement 316
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page vii

CONTENTS vii

Determinants 317
Mechanisms 322
Distribution 323
Relation to Rates and Risks 336
Relation to Other Factors 339
Prevention and Control 341
Current Issues 351
References 352

Chapter 13 Diabetes and the Metabolic Syndrome 361

Summary 361
Introduction 362
Concepts and Definitions 363
Measurement 366
Determinants 367
Mechanisms 368
Relation to Other Factors 369
Distribution 369
Rates and Risks 375
Prevention and Control 382
Current Issues 387
References 389

Chapter 14 Smoking and Other Tobacco Use 395

Summary 395
Introduction 395
Concepts and Definitions 396
Measurement 397
Determinants 398
Mechanisms 398
Distribution 400
Relation to Rates and Risks 404
Relation to Other Factors 414
Prevention and Control 414
Current Issues 424
References 425

Chapter 15 Other Personal Factors 431

Summary 431
Alcohol Consumption 433
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viii CONTENTS

Adverse Psychosocial Factors 447

Hemostatic Factors 464
Evolving and Emerging Factors 476
References 491

Chapter 16 Social and Physical Environment 503

Summary 503
Introduction 503
Social Status 505
Changes in Social Conditions 512
Particulate Air Pollution 522
Neighborhood Characteristics 524
Current Issues 527
References 528

PART IV—CAUSATION AND PREVENTION: THEORY, PRACTICE, AND FURTHER RESEARCH 533

Chapter 17 What Causes Cardiovascular Diseases? 535

Summary 535
Introduction 535
Causal Judgment 536
Causal Constructs 540
Causation of Atherosclerotic and Hypertensive Diseases 543
Conclusion 547
Current Issues 547
References 548

Chapter 18 Strategies of Prevention 551

Summary 551
Introduction 551
Concepts and Language of Prevention 552
Strategies of Prevention 557
Intervention Approaches 560
A Developing Country Perspective 561
Current Issues 563
References 565
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page ix

CONTENTS ix

Chapter 19 Evidence and Decision Making 567

Summary 567
Introduction 567
Nature of Evidence 569
Evidence-Based Decision Making 570
Approaches to Evaluation of Evidence 573
Current Issues 587
References 587

Chapter 20 Recommendations, Guidelines, and Policies 591

Summary 591
Introduction 592
Clinical Guidelines 594
Community Guidelines 607
Public Policies 609
Current Issues 613
References 614

Chapter 21 The Case for Prevention 619

Summary 619
Introduction 619
Experience with Multifactor Primary Prevention 621
The Burden of Risk 636
Economic Considerations 640
Models for Explanation and Prediction 642
Visions of Success in CVD and Chronic Disease Prevention 646
Counter-Arguments 648
Current Issues 649
References 649

Chapter 22 Taking Action 657

Summary 657
Introduction: Calls to Action 657
Overview: Goals, Strategies, and Action Plans 658
Case Study: A Public Health Action Plan to Prevent Heart Disease and Stroke 665
Obstacles to Taking Action 669
Current Issues 673
References 675
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x CONTENTS

Chapter 23 Epidemiology and a CVD Prevention Research Agenda 679

Summary 679
Introduction 680
Concepts of Epidemiology 681
Goals 682
Strategies of Investigation 683
Proposed Research Agendas 685
Capacity Requirements 690
Populomics: The Population Context of Research on Health 692
Current Issues 693
References 693

INDEX 697
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page xi

Foreword

P
ublication of this second edition of Dr. Darwin life for which the human species has not been adapted
Labarthe’s invaluable book, Epidemiology and over the 2–4 million years of hominid/hominoid evo-
Prevention of Cardiovascular Diseases: A lution; their roots are mass “. . . disturbances of hu-
Global Challenge is most opportune: As Dr. Labarthe man culture . . .” (Rudolf Virchow)—generalizations
emphasizes, the CVD prevention effort at this fully applicable/valid for the CVD epidemic, as this
juncture—50 years down the road—confronts both monograph details. To end the CVD epidemic, the
“. . . considerable challenges and immense opportu- sine qua non is rectification of the multiple distur-
nities . . . .” On the one hand, the CVD epidemic per- bances in human culture causing it—a proposition re-
sists; on a global scale it is waxing—indeed a peatedly verified as valid by the history of conquest of
challenge. And the challenge holds also for countries earlier epidemics (e.g., tuberculosis, pellagra, rickets).
like the United States, where epidemic CVD persists The opportunities to conquer the CVD epidemic
despite substantial declines in coronary/stroke death are indeed immense. First and foremost, prerequisite
rates during the latter decades of the 20th century. The knowledge concerning the etiology of the CVD epi-
current situation in the United States is problematic— demic: the data base (already substantial 50 years
as this book documents—making the challenges con- ago) is now vast—extensive concordant data, world-
siderable indeed: tapering or cessation in recent years wide in scope, accumulated over decades by epidemi-
of down trends in CVD mortality and in major CVD ology and every other research methodology available
risk factor levels (e.g., for saturated fat and cholesterol to medicine. Critical detailed information on the mul-
intakes, and for diet-dependent serum cholesterol and tiple causes of epidemic CVD is in hand—and for
blood pressure); epidemic obesity with its conse- prevention of mass disease, such information on cau-
quences, including rampant incidence of diabetes and sation, the “question of questions,” is decisive. We
other obesity-driven metabolic CVD risk factors; un- know in depth what needs to be done—at every level
abated high salt intake; overall dietary and physical of prevention—to break links in the chain of causa-
activity patterns still generally adverse population- tion, including for primary and primordial prevention,
wide including among children and teenagers; all too i.e., the prevention in the first place (from precon-
many still smoking, all too many teenagers becoming ception on) of the adverse lifestyles and the lifestyle-
smokers; even more so for lower socioeconomic strata related established major risk factors. Crucial to this
of all ethnicities, hence paltry proportions of all strata effort are improved eating patterns, Mediterranean
at low CVD risk––a critical index––and little or no ev- and East-Asian style cuisines updated for this cen-
idence of a sustained upward slope in this index; in the tury, especially as to lower salt, plus moderation in in-
media, especially TV, an on-going flood of promotions takes of alcohol, fats, and total calories—along with
of foods/beverages harmful for heart health; in med- regular frequent exercise and non-smoking. The up-
ical practice, overwhelming reliance on a high risk date for the 21st century—derived from the research
strategy (reactive, not proactive) to cope with these achievements of the last 50 years—gives an enhanced
challenges––a focus on detection of people who al- nutrient intake pattern: as earlier, low in saturated
ready have a high level of the established major CVD fats and cholesterol; reduced in total fats; enhanced
risk factors and their long-term treatment with med- in polyunsaturated fats; calorie controlled; plus free
ications (in 2008, 320.4 million prescriptions for an- of trans fats; much lower in salt; reduced in sugars es-
tihypertensive and 139.6 million prescriptions for pecially separated sugars (e.g., from sweetened bev-
antihypercholesterolemic drugs, as reported by the erages); enhanced in total protein, especially vegetable
AARP). However useful for patients already at high protein (lower in animal protein from meats); for those
CVD risk, this limited one-sided strategy relying on who drink, moderate (not excessive) in alcohol; en-
pills as the remedy begs the basic issue: Epidemics hanced in potassium/calcium/magnesium/phosphorus/
are due to population-wide exposures to new ways of non-heme iron, the vitamins, and fiber (from whole

xi
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page xii

xii FOREWORD

grains/beans/vegetables/fruits). As this enumeration prevention/control. Repeatedly, the public has been re-
indicates, the research findings (including from sponsive and substantial progress (albeit incomplete)
population-based observational studies and clinical tri- has been achieved, despite opposition from special
als) document the multifaceted dietary imbalances–– interests (including sectors of the food and beverage
concurrent excesses and inadequacies––now industries, the big tobacco companies)––e.g., in the
implicated in the etiology of the CVD epidemic and United States, sizable declines in intakes of saturated
its diet-related major metabolic risk factors. Con- and trans fats, total fats, cholesterol; the related de-
sequent recommendations enable variegated ap- crease in adult population average serum cholesterol
proaches to modern delightful eating styles assuring from about 240 mg/dl 50 years ago to about 200
avoidance/rectification of these imbalances. mg/dl by the year 2000, achieving a national public
These eating styles, along with regular frequent health goal; marked falls in the prevalence of cigarette
exercise, offer the potential for all population strata smoking; associated declines––in the order of 50% or
(socioeconomic/ethnic) to prevent/check/correct the more—in mortality from CHD and stroke, with con-
nowadays still usual development of adverse levels sequent addition of years to life expectancy for young,
of major metabolic risk factors: serum total/LDL/ middle-aged, and older adults. And, in several coun-
VLDL/HDL cholesterol; blood pressure; plasma glu- tries, as well as internationally, there are significant so-
cose; weight; and they go beyond these merits, since cial movements in place, supporting/encouraging the
adverse eating patterns produce excess CVD risk over effort, bringing together health professionals and lay
and above their adverse influences on these metabolic leaders in effective alliances. As Dr. Labarthe notes, this
risk factors. too is an important component for a successful pre-
So the opportunities are truly immense, as Dr. vention effort—important today for CVD, as it was in
Labarthe emphasizes. Their scope encompasses po- the 19th century for TB control. All these are indeed
tential for realization of the critical goal: continuous solid bases for accomplishment of next key tasks.
progressive enhancement in the coming years/decades As noted repeatedly, this book is replete with
of the percent of the population at low risk, so that many-sided up-to-date information invaluable for
for most people—not just a small minority—CVD every person concerned with the CVD prevention
risk is miniscule; they are freed of the burden of epi- effort. It is a fitting product of Dr. Labarthe’s ex-
demic CVD, with consequent enhanced longevity traordinary capacities and experiences over decades—
with health. High stakes indeed! as a colleague, teacher, researcher, public health
The opportunities are immense also because on a leader—in academia, at the CDC, at local/national/
world scale and in several regions of the world, pub- international learning venues, including the seminal
lic policy is in place at the national level (including in US and International Ten Day Teaching Seminars on
the United States), policy committed to the accom- CVD Epidemiology and Prevention he has effectively
plishment of CVD prevention through a two-pronged led for years.
strategy (population-wide and high risk) emphasiz- On a personal note, over 40 years ago when I au-
ing improved lifestyles. In a few places, public policy thored an early monograph on this same subject, it was
specifically includes priority for achieving the deci- my privilege for it to have a Foreword by Paul Dudley
sive goal of progressively increasing the percentage of White, MD––distinguished cardiologist, statesman,
the population at low risk. In the United States, sub- world leader, humanist/humanitarian. Its opening sen-
stantial funds have recently been allocated—specifically tence read, “Dr. Jeremiah Stamler has written the book
to the national Centers for Disease Control and on Preventive Cardiology that I would liked to have
Prevention (CDC)—for the CVD prevention effort. written.” Today these words are mine in regard to
Opportunities are immense also for this effort this volume by Darwin Labarthe.
because many countries—ranging from Finland to
Japan to the United Kingdom and the United States— Jeremiah Stamler, MD
have already over decades accrued extensive positive Professor Emeritus
experiences with sustained public health efforts to Feinberg School of Medicine
improve lifestyles, thereby control lifestyle-related Northwestern University
major CVD risk factors, and contribute to CVD Chicago, Illinois
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page xiii

Preface

The central messages of this second edition are these: change on the context and content of the book is sub-
(1) Cardiovascular diseases remain the foremost stantial; however, it is necessary to underscore the
causes of preventable death globally and con- disclaimer that the views expressed throughout are
tinue to grow in prominence, because of their personal and are not intended to represent the official
attendant burden, disparities, and costs. position of the US Centers for Disease Control and
(2) Epidemiology has contributed immeasurably Prevention (CDC) or the US Department of Health
to a vast body of knowledge about the causes and Human Services (DHHS).
and means of prevention of these and related The book has changed principally in presenting
conditions, but this knowledge has yet to be greater emphasis on public health in cardiovascular
applied on a sufficient scale to confer its po- disease prevention while retaining its epidemiologic
tential societal benefit. content. The intent has been to increase the book’s
(3) Public health is accountable for putting this value for both epidemiologists and public health pro-
knowledge more fully to work by setting fessionals by bringing the original content up to date
goals, devising strategic plans and policies, in Parts I–III and expanding discussion of how epi-
implementing targeted actions, and docu- demiology is translated into policy and practice in
menting their impact in improving the health Part IV.
of populations. Currency has been achieved by including more
than 1600 citations and nearly 400 tables and fig-
These messages are consistent with the content of ures, many from recent sources; rewriting the chap-
the first edition but have gained force from develop- ters on the major cardiovascular diseases and their
ments in the intervening decade: increased awareness determinants; introducing a chapter on genomic epi-
of the global burden of cardiovascular diseases, with demiology; and expanding discussion of the global di-
their immense social and economic consequences; a mensions of CVD. For many sources, URLs are
growing sense of need to integrate approaches to car- included to permit continuing access for interested
diovascular diseases with prevention of other chronic readers.
or noncommunicable diseases, with transformation of New chapters in Part IV address strategies of pre-
health systems to address them coherently; and the vention as part of a recently developed action frame-
ever more urgent goal to reduce the mounting burden, work; the nature of evidence for prevention, and
disparities, and costs of these diseases. Epidemiology, methods for its evaluation as practiced by several
through its applications in development, adoption, leading authoritative bodies; current national, re-
and implementation of health policy and in public gional, and global recommendations, guidelines, and
health practice, is fundamental to achieving this goal. policies for prevention of CVD and other major
It is the author’s hope that this new edition will con- chronic diseases; the case for CVD prevention at in-
tribute to this effort. dividual and population levels; and action plans
The difference of a decade is due importantly to adopted for implementation in the United States,
advances in science and practice that better inform our Europe, South Asia, and worldwide. Expansion in
understanding of the need and opportunity for effec- these areas had one regrettable cost—lack of updates
tive action. From the start of this past decade, the on rheumatic heart disease, Chagas’ disease, con-
perspective of the author, too, has advanced—from genital heart disease, and Kawasaki disease—which
that of the academic epidemiologist to that of the are treated only in the first edition.
public health practitioner. This was a result of un- Features retained in the second edition include the
dertaking a US governmental role at the federal level basic structure in which the public health perspec-
and the greatly enhanced public health experience af- tive is introduced in Part I; the major atherosclerotic
forded by this opportunity. The influence of this and hypertensive diseases are discussed in Part II;

xiii
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xiv PREFACE

their main determinants are reviewed sequentially in case represents an exhaustive systematic review, al-
Part III; and implications of this evidence for theory, though those of others are cited extensively. Closing
practice, and research are discussed in Part IV, which each chapter is a more or less speculative suggestion
concludes with a chapter on CVD epidemiology of the of current issues most important for further discus-
future—the rich and varied research opportunities sion. In these ways the text is intended to stimulate
presented and the place of epidemiology as the core thinking and debate. The author welcomes comments,
discipline of “populomics,” the scientific foundation queries, and criticisms from readers.
of population health. A historic perspective is also A Chinese proverb says, “Teachers open the door
retained, although this is not meant to recount the his- but you must enter by yourself.”1 It is hoped that the
tory of the field, which is being done in a far more ef- material that follows will open many doors for stu-
fective way elsewhere. The purpose instead is to dents and practitioners of CVD prevention and pub-
illustrate wherever appropriate the key studies that, lic health, revealing a world of opportunity for
from early in the development of CVD epidemiology, fulfilling our highest obligation: to assure conditions
have made fundamental and lasting contributions to in which people can be healthy.
our current knowledge.
Throughout the book, the unifying approach of
a single author has the advantage of a consistent pre- Reference
sentation and coherent interpretation across the many
topics addressed. There is room for differing opinion 1. Schiller D. The Little Zen Companion. New
and further exploration of many topics raised. The York: Workman Publishing; 1994.
content reflects one person’s perspective and in no
46394_FM_00i_xviii.qxd 2/26/10 2:30 PM Page xv

Dedication

This book is dedicated to all whose work is reflected here

and to all who will contribute to advances in the understanding
of cardiovascular diseases and reduction of the public health
burden they represent throughout the world.

xv
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Acknowledgments

Technical assistance in bibliographic work was pro- George Howard, William Kannel, Thomas Kottke,
vided with diligence and skill by T. Christopher Bond; Ian MacMahon, Henry McGill, Kenneth Pelletier,
the permissions process was supported by Tiffany Douglas Schocken, Richie Sharrett, Jeremiah Stamler,
Lynn Williams and by Anthony Omokheowa Anani Elaine Stone, Jack Strong, and Thomas Thom.
and Elohor Anani. Several peer reviewers provided valuable com-
Contributions of critical points of information ment and suggestions. Although their anonymity pre-
were made by Patty Borhani, Ross Brownson, Michele cludes personal recognition, it is hoped that they will
Casper, Elizabeth Barrett-Connor, Rory Collins, see their input reflected in the final product.
Leonard Cook, Jeffrey Cutler, Jack Farquhar, Lawrence Merrily Labarthe deserves boundless gratitude for
Green, Nancy Haase, Millicent and Ian Higgins, her support and forbearance throughout this project.

xvii
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46894_CH01_001_018.qxd 2/25/10 3:22 PM Page 1

P A R T
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