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Journal of Lipid Research, Vol. 47, 1-14, January 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost¹

Daniel Steinberg²

Department of Medicine, University of California–San Diego, La Jolla, CA

¹ Based in part on the author's book in preparation, The Cholesterol Wars.

Published, JLR Papers in Press, October 15, 2005.

³ The panel included Fredrickson, Chair; Edwin L. Bierman, Professor of Medicine, University of Washington; David H. Blankenhorn, University of Southern California; William Castelli, Framingham Heart Study, National Heart and Lung, Institute (NHLI); William E. Connor, University of Iowa; Gerald R. Cooper, Communicable Disease Center; Theodore Cooper, Director, NHLBI; Seymour Dayton, VA Medical Center, Los Angeles; Howard Eder, Albert Einstein College of Medicine; Ivan D. Frantz, University of Minnesota; William Fridewald, NHLBI; DeWitt S. Goodman, Columbia University; Frederick T. Hatch, University of California Berkeley; Richard J. Havel, University of California San Francisco; Peter Koo, University of Pennsylvania; Robert S. Lees, Massachusetts Institute of Technology; Robert I. Levy, NHLBI; Robert P. Noble, Sharon Research Institute; Isidore Rosenfeld, Cornell University; and Daniel Steinberg, University of California San Diego.

⁴ The participating centers were at Baylor College of Medicine under Antonio M. Gotto; University of Cincinnati Medical Center under Charles J. Glueck; George Washington University Medical Center under John C. LaRosa; University of Iowa Hospitals under William E. Connor and, later, Francois Abboud and Helmut Schrott; Johns Hopkins Hospital under Peter O. Kwiterovich; University of Minnesota under Ivan D. Frantz, Jr., and Donald B. Hunninghake; Oklahoma Medical Research Foundation under Reagan H. Bradford; Washington University School of Medicine under Gustave Schonfeld; University of California San Diego under W. Virgil Brown and Daniel Steinberg and, later, Fred H. Mattson; University of Washington under William R. Hazzard and Edwin L. Bierman and, later, Robert H. Knopp; Stanford University under John W. Farquhar; and University of Toronto and McMaster University under J. Alick Little.

⁵ The original Intervention Committee appointed in 1971 included Daniel Steinberg and John W. Farquhar, cochairs; William R. Hazzard; Edmond A. Murphy; Al Oberman and Richard D. Remington, members at large; Dale Williams and James E. Grizzle as Data Coordinating Center representatives; and Robert I. Levy and Basil Rifkind, National Heart and Lung Institute staff. Membership was later expanded to include William E. Connor; G. William Benedict; C. E. Davis; Ronald W. Fallat; Antonio M. Gotto; Richard C. Gross; Donald B. Hunninghake; John C. LaRosa; Maurice Mishkel; Gustav Schonfeld; L. Thomas Sheffield; Thomas F. Whayne, Jr.; and Richard J. Havlik representing the Program Office.

⁶ The Planning Committee was made up of Basil M. Rifkind, Chair; Susan Clark, Michael J. Bernstein, and Larry Blaser, representing the Office of Medical Applications of Research; Charles Glueck, Cincinnati General Hospital; William Hazzard, Johns Hopkins Medical School; Kenneth Lippel, Program Coordinator of the Atherogenesis Branch of NHLBI; and Albert Oberman, University of Alabama Medical Center.

⁷ The Consensus Development Panel members were Daniel Steinberg, MD, PhD, Chair, University of California San Diego; Sidney Blumenthal, MD, Columbia University; Richard A. Carleton, MD, Brown University; Nancy H. Chosen, AB, JD, public interest attorney; James E. Dale, MD, MPH, University of Massachusetts Medical School; John T. Fitzpatrick, Esq., Attorney at Law and past President of the American Heart Association; Stephen B. Holley, MD, MPH, University of California San Francisco; Robert W. Mahley, MD, PhD, Director of Gladstone Foundation Laboratories, University of California San Francisco; Gregory O'Keefe III, MD, Islands Community Medical Center, Vinalhaven, Maine; Richard D. Remington, PhD, University of Iowa; Elijah Saunders, MD, University of Maryland School of Medicine; Robert E. Shank, MD, Washington University School of Medicine; Arthur A. Spector, MD, University of Iowa; and Robert W. Wissler, MD, PhD, University of Chicago.

² To whom correspondence should be addressed. e-mail: dsteinberg{at}ucsd.edu

As of the early 1980s, despite the wealth of evidence from experimental animal models, the extensive epidemiologic evidence, the powerful genetic evidence, and the strongly suggestive clinical intervention trial results, most clinicians still remained unpersuaded regarding the relevance of the lipid hypothesis. What was needed was a well-designed, large-scale, long-term, double-blind study demonstrating a statistically significant impact of treatment on coronary heart disease events. The National Institutes of Health (NIH) had laid the groundwork for such a study as early as 1970, but the study was not completed and the results published until 1984. This study, the Coronary Primary Prevention Trial, showed that treatment with a bile acid binding resin reduced major coronary events in hypercholesterolemic men by 19%, with a P value of 0.05. The NIH followed this up with a national Consensus Development Conference on Lowering Blood Cholesterol to Prevent Heart Disease. For the first time, the NIH now went on record advocating screening for hypercholesterolemia and urging aggressive treatment for those at high risk. The Institute initiated a national cooperative program to that end, the National Cholesterol Education Program. For the first time, preventing coronary heart disease became a national public health goal.

Supplementary key words cholestyramine • National Cholesterol Education Program • coronary heart disease

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