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

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. 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. As early as 1970, many of the country's experts in atherosclerosis and preventive cardiology, and the American Heart Association, were already convinced that there was a causal connection between blood cholesterol and coronary heart disease, as discussed in the earlier installments of this series (1Steinberg D. An interpretive history of the cholesterol controversy. Part I.J. Lipid Res. 2004; 45: 1583-1593Google Scholar, 2Steinberg D. An interpretive history of the cholesterol controversy. Part II. The early evidence linking hypercholesterolemia to coronary disease in humans.J. Lipid Res. 2005; 46: 179-190Google Scholar, 3Steinberg D. An interpretive history of the cholesterol controversy. Part III. Mechanistically defining the role of hyperlipidemia.J. Lipid Res. 2005; 46: 2037-2051Google Scholar). However, no one could be certain how firm that connection was or how much impact treatment to decrease cholesterol levels would have. As a result, almost no nonspecialists, and in fact very few practicing internists or cardiologists, were paying very much attention to their patients' high blood cholesterol levels in 1970, and coronary heart disease continued to be the number one cause of death. What to do? The National Institutes of Health (NIH) realized that launching a national program to treat high blood cholesterol levels would be enormously complex and expensive. They could not justify that expense without first having iron-clad proof that treatment would work. 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