Steinberg - The cholesterol wars: the skeptics vs. the preponderance of evidence

THE CHOLESTEROL WARS

The Skeptics vs. the Preponderance of Evidence

Daniel Steinberg, M.D., Ph.D.

University of California, San Diego

Academic Press

Dedication

To the hundreds of scientists, clinicians and associated research personnel who over many years amassed the evidence that hypercholesterolemia is a key causative factor in atherosclerosis; and to the thousands of volunteers who agreed to participate in the critically important clinical trials that closed the case, inaugurating a new era in preventive cardiology.

Front Matter

Copyright

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First edition 2007

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ISBN: 978-0-12-373979-7

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FOREWORD

The bravest are surely those who have the clearest vision of what is before them.

Thucydides, 404 BC

The tradition of chronicling wars while they are being fought was initiated in the 5th century BC with the description of the Peloponnesian Wars by Thucydides, a general in the Athenian army. That noble tradition is extended in elegant fashion in this book by Daniel Steinberg, a general in the Cholesterol Wars. The Cholesterol Wars began nearly 100 years ago in Russia when a young pathologist, Nikolai Anitschkow, fed cholesterol to rabbits and produced atherosclerosis of the arteries. This experiment and subsequent epidemiologic studies triggered a passionate debate as to whether cholesterol is the root cause of human atherosclerosis, the disease process that underlies heart attacks and strokes. The stakes were high. Throughout the 20th century, while the cholesterol battles were raging, more people were dying of atherosclerosis than were killed in military combat.

). The speaker was characterizing attitudes as recent as the 1990s.

While these battles were being fought, public health authorities in the U.S., U.K., and elsewhere hesitated to make the general recommendation of aggressive cholesterol lowering to society as a whole. This inexplicable delay resulted in widespread public confusion and cost many thousands of lives. For the anti-cholesterol forces, it is still too early to declare mission accomplished. Although mortality from heart attacks and strokes has been reduced, these catastrophes are still major killers.

). This conclusion has been reinforced recently with the discovery of a common genetic trait in African-Americans that lowers blood LDL-cholesterol levels by only 28 percent throughout life, yet leads to an 88 percent reduction in coronary heart disease in the sixth and seventh decades despite contributory risk factors that include hypertension and diabetes. This 88 percent reduction in coronary events is much greater than the 3040 percent reduction that is attained when LDL-cholesterol levels are lowered by diet or drugs that are started many years after the atherosclerotic process has developed.

Autopsy studies, such as those on young men who died in the Korean War, have documented that the earliest hallmarks of atherosclerosis begin before 20 years of age. While few would suggest aggressive LDL lowering for most teenagers, there must be a time between age 20 and 40 when it is appropriate to begin careful attention to plasma LDL-cholesterol in everyone. The standard intervention is a low-cholesterol, low-fat diet that is relatively rich in polyunsaturated fatty acids. When consumed faithfully over a lifetime, as it was in China and Japan before recent times, such diets lower plasma LDL-cholesterol sufficiently to reduce the incidence of heart attacks by more than 90 percent. Yet, as Steinberg suggests, it would take decades to change the dietary habits of Americans sufficiently to make such an impact. Moreover, the economic and social consequences would be great. Thus, it is likely that we will see more widespread use of LDL-lowering drugs such as statins and cholesterol absorption inhibitors. All evidence predicts that these drugs would lower markedly the heart attack burden if they were started early enough. Yet, as Steinberg documents, the remaining skeptics still challenge the wisdom of such widespread use.

When a scholarly book like this one is published, the question always arises as to who should read it. In our opinion, The Cholesterol Wars: The Cholesterol Skeptics vs. the Preponderance of Evidence should certainly be read by anyone who is in a position to influence public policy toward health issues. It should also be read by all physicians who care for patients at risk for heart disease or stroke. Finally, it should be read by members of the general public who are puzzled by the conflicting claims about cholesterol that continue to be made. Armed with the facts outlined in this book, any individual will be fully equipped to stake out an informed position in the next Cholesterol War.

Michael S. Brown, Joseph L. Goldstein

University of Texas Southwestern Medical Center, Dallas, Texas, USA

PREFACE

The thesis of this book is that the importance of hypercholesterolemia in human atherosclerosis should have been and could have been appreciated decades earlier than it was. The opportunities that were missed and the findings that went unappreciated because of preconceived mindsets are reviewed and analyzed. The history of the controversy is intrinsically of interest. In addition, there may be lessons to be learned from that history that could provide guidance in dealing with controversies yet to come.