Acknowledgments

I dedicate this book to my wife Susan, who has not only encouraged and supported me at every step, but who has also shared the insights she gained during her years at the Chicago chapter of the American Heart Association in the late 1970s, where she helped coordinate public smoking, blood pressure, and diet education campaigns. Her stories about their successful efforts to persuade city restaurants to ban cigarettes helped put a human face on the vital impact of local volunteer organization in the battle against cardiovascular disease. She has patiently listened to me try out my ideas on her. No one could wish for a better partner in life.

I also want to express special thanks to my dear friend Debra Roney for her wonderful illustrations of atherosclerotic plaques (Figure 5.2), the coronary arteries (Figure 10.1), and the cardiac conduction system (Figure 12.1).

I am also deeply indebted to the NIH—and specifically the NHLBI—where I am fortunate to have spent most of my career. I could not have hoped to find a more supportive professional environment or one that better embodies the values of scientific rigor and integrity. Working at the NHLBI has enabled me to join a community of talented and dedicated professionals at NIH and at the institutions it serves in an extraordinary enterprise far larger than ourselves, guided by the twin goals of advancing human knowledge and ameliorating human disease. I have had the good fortune to work with many brilliant and dedicated colleagues on the studies described in this book over the course of my long career—too many to acknowledge individually here. However, I want to specifically thank George Mensah who invited me in 2016 to collaborate with him on an article for Circulation Research about the decline in cardiovascular mortality, which was the starting point for the present book. I also want to acknowledge another co-author of that article, Michael Mussolino, who provided the health statistics for that article, which I have also used liberally in this book. Additionally, I want to thank Jeff Cutler for his constructive feedback on the first draft of this book and Jacques Rossouw for his historical perspective on the Women’s Health Initiative.

I also want to express my deep gratitude and affection to my early mentors, who introduced me to cardiovascular epidemiology and clinical trials and without whom I might never have found my calling: Basil Rifkind (who gave me my first opportunity in this field and supported me at every turn), Al Tyroler and Gerardo Heiss (who supervised my Masters research), and Dale Williams and Ed Davis (who welcomed me to their Lipid Research Clinics Data Coordinating Center in Chapel Hill in 1979–84).

I also want to acknowledge the many other collaborators and friends—too numerous to name here—that I have made in my 42 years at NIH. These include my former NHLBI colleagues, many of whom worked on projects cited in this book: Robin Boineau, Bryan Brewer, Denis Buxton, James Cleeman, Patrice Desvigne-Dickens, Ray Ebert, Debra Egan, Lawrence Fine, Jerome Fleg, William Friedewald, Larry Friedman, Nancy Geller, Suzanne Goldberg, Ronald Goor, Max Halperin, Ahmed Hasan, Tracy Hoke, Erin Iturriaga, Ruth Kirby, Michael Lauer, Eric Leifer, Alice Mascette, Marissa Miller, Stephen Mockrin, Chuke Nwachuku, Gerald Payne, Gail Pearson, Michael Proschan, Diane Reid, Yves Rosenberg, Beth Schucker, Monica Shah, Susan Shurin, Sonya Skarlatos, Joni Snyder, George Sopko, Paul Sorlie, Wendy Taddei-Peters, Momtaz Wassef, and Gina Wei. They also include my many collaborators and friends outside the walls of NIH: Colin Baigent, Noel Bairey Merz, Elizabeth Barrett Connor, Reagan Bradford, Maria Brooks, Barry Davis, Katherine Detre, Robert Frye, Curt Furberg, Saul Genuth, Scott Grundy, David Herrington, Judith Hochman, Howard Hodis, Donald Hunninghake, Anthony Keach, James Knoke, Lewis Kuller, Gervasio Lamas, John LaRosa, Jay Mason, Lemuel Moyé, Pamela Ouyang, Marc Pfeffer, Bertram Pitt, Stuart Pocock, Jeff Probstfield, Paul Ridker, Robert Simari, Neil Stone, Jonathan Tolbert, Joel Verter, David Waters, Paul Whelton, Janet Wittes, Jackson Wright, and Faiez Zannad. Thanks also to those who have shared their ideas or listened to or critiqued my ideas at a scientific symposium or in a casual conversation, and those whose journal articles I have read or who have read mine. To the many who have influenced my thinking and understanding in unknowable ways, I hope this book reflects well on what you have taught me.

Finally, I want to gratefully acknowledge the thousands of volunteers who have selflessly participated in the many cardiovascular clinical trials chronicled in this book. If it takes a village to raise a child, it takes a good-sized city to achieve the successes our community has realized together.

Preface

On a brisk October day in 1978, barely a year after I came to work as a medical officer for a major National Institutes of Health (NIH)-sponsored cholesterol trial, I took my seat in the back row of a conference room in Bethesda, Maryland, as an international group of experts convened to review the evidence of a promising recent trend in mortality from heart attack and stroke in the U.S. and abroad.¹ Speakers included such major luminaries in the relatively new field of cardiovascular epidemiology as Nemat Borhani, Fred Epstein, Lew Kuller, Framingham leader Bob Garrison, and NIH health statistics guru Thomas Thom. And, of course, prominently featured was the father of preventive cardiology, Jeremiah Stamler, then approaching age 60, who had famously faced down the House Un-American Activities Committee in 1965 and defeated them in the Supreme Court, and who remains a fierce and productive advocate of cardiovascular health 42 years later.² The speakers list and audience also included many of rising stars in the field. After two days, the conferees concluded that heart attacks and strokes had indeed declined by as much as 25% since 1968, although they could not pin down exactly why.

This seemingly modest decline in heart attacks and strokes was actually a very big deal. It may surprise you to know that the 1960s were not only an era of social turmoil and upheaval, but also a decade in which more than 6.3 million Americans died of heart disease (mainly heart attacks) and another 1.8 million died of strokes.³ The per capita death toll from heart disease in the 1960s was higher than in any decade before or since and the total was 110 times the 58,220 U.S. fatalities recorded during the entire Vietnam War.⁴ Yet as a medical student in the late 1960s and early 1970s, I had a blasé attitude toward heart attacks. Yes, heart attacks were the number one cause of death by far in the U.S. and other developed countries, causing twice as many deaths as cancer (which ranked second), but didn’t they happen mainly to old people seemingly as the end result of a degenerative process of aging, i.e., hardening and narrowing of the arteries which provide the heart with blood and oxygen? From the distant perspective of a 32-year-old man, I thought this was sad, but we are not meant to live forever.

Now, to be sure, heart attacks did not happen only to the elderly, but too often struck in middle age, especially in middle-aged men with a family history of high cholesterol and early heart disease. While most of the 8.2 million cardiac deaths in the 1960s occurred in older persons, approximately one-third of all cardiac deaths in 1968–77 occurred before age 65—about 20% before age 45 and another 20% between ages 45 and 54.⁵ Thus, it was not unusual for seemingly healthy middle-aged men and even women to be stricken down at the peak of their productivity, leaving their dependent families bereft. I had witnessed this phenomenon first-hand in my own circle of acquaintances. Indeed, the cholesterol trial I was working on in 1978 specifically focused on otherwise healthy “middle-aged” men, aged 35–59, with high cholesterol, who were thought most susceptible to a “premature” heart attack and thus most likely to benefit from a cholesterol-lowering drug.

In 1978, no one really knew whether the recent 25% decline in mortality from heart attacks and strokes was just a chance fluctuation or the beginning of a trend, or (if the latter) what factors were responsible. The ensuing four decades have brought clarity. As of 2017, heart attack mortality rates had fallen by 81% since their peak in 1968.⁶ Stroke mortality rates fell by 77% during this same period, continuing a trend that began 60 years earlier. This progress has been hard won by a combination of basic and applied laboratory research, broad and far-reaching epidemiological studies, and expensive multiyear clinical trials in human volunteers. Occasionally, the road to progress has been easy and direct; more often it has been marked by false starts, setbacks, detours, dead ends, and outright failures. But science thrives on the failure of its favored hypotheses to pan out. Human inquiry generally begins with an observation and a question—How? Why? What if?—and progresses to a theory. What distinguishes scientific from other kinds of inquiry is a compulsion to put our theories and explanations to a test, to disprove old truths, and replace them with new truths. In science, all truths are tentative. Science takes to heart Alexander Pope’s dictum that “no one should be ashamed to admit they are wrong, which is but saying, in other words, that they are wiser today than they were yesterday.”⁷

Today, our basic understanding of why people have heart attacks and strokes has been revolutionized, and effective treatment options have multiplied. Cardiovascular disease is no longer viewed as an inevitable feature of the natural course of aging, and complacency has given way to hope. In this book, I will offer my inside look as a 42-year NIH employee at how this remarkable success was achieved. It is a multifaceted story with many unexpected twists. Sometimes I can speak as an active player in this community enterprise, other times as a colleague or adviser, and occasionally as the proverbial fly on the wall. I hope to hit the highlights without overly dwelling on statistical detail, but some statistics are essential to the story. I will focus on developments that have demonstrably influenced the course of the rise and decline of cardiovascular mortality since 1900, but my story will also include a few notable dry wells. If this story is comparable to an Agatha Christie whodunit, it is The Murder on the Orient Express.⁸ Multiple suspects had a hand in it.

1. Proceedings of the Conference on the Decline in Coronary Heart Disease Mortality: National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, Maryland. NIH publication no. 79–1610, 1978. Bethesda, MD: National Heart, Lung, and Blood Institute, NIH, 1979, Oct 24–25.

Chartbook for the Conference on the Decline in Coronary Heart Disease Mortality. Hyattsville, MD: NCHS, 1978. National Center for Health Statistics.

2. C Dampier. At age 100, the father of preventive medicine is going strong—as living proof that he was right all along. Chicago Tribune, December 26, 2019. https://www.chicagotribune.com/lifestyles/ct-life-100-year-old-scientist-stamler-20191226-jeprzoeqazha7nuvs2prfcndwy-story.html.

3. Centers for Disease Control and Prevention (CDC), National Center of Health Statistics. Leading Causes of Death, 1900–1998.

4. National Archives, Vietnam War U.S. Military Fatal Casualty Statistics, Electronic Records Reference Report, https://www.archives.gov/research/military/vietnam-war/casualty-statistics.

5. MD Ritchie, HK Wall, MG George, JS Wright. U.S. trends in premature heart disease mortality over the past 5 years: Where do we go from here? Trends in Cardiovascular Medicine 2020, 30:364–374. Doi: org/10.1016/j.tcm.2019.09.005. https://reader.elsevier.com/reader/sd/pii/S1050173819301343?token=7F40CE58241E384675154F72DB6A47DA204635AA02005A37DE85A7A8ED4F1F679D9F00D9FDE3E1D64DC89666494E1ED0.

6. GA Mensah, GS Wei, PD Sorlie, LJ Fine, Y Rosenberg, PG Kaufmann, ME Mussolino, LL Hsu, E Addou, MM Engelgau, D Gordon. Decline in Cardiovascular Mortality: Possible Causes and Implications. Circ Res 2017:366–380. doi:10.1161/CIRCRESAHA.116.309115.

7. AZ Quotes—Alexander Pope. https://www.azquotes.com/author/11775-Alexander_Pope.

8. A Christie. Murder on the Orient Express. London: Collins Crime Club, 1934.