More than 10 million individuals in the United States currently have symptomatic
coronary artery disease (CAD). Asymptomatic CAD is even more prevalent. CAD in the United States is responsible for approximately 1.5 million
myocardial infarctions, 500,000 deaths, and a total economic burden in excess of $120 billion annually. Fortunately, CAD is preventable in many individuals. Our understanding of CAD has steadily progressed throughout the 20th century, and now several lines of evidence support the importance of
cholesterol in both the genesis and management of
coronary atherosclerosis. Following identification of the presence of
cholesterol in
atheromas, Anitschkov early this century demonstrated that atherosclerotic lesions can be induced in susceptible animals by high-saturated-fat and
cholesterol diets. These lesions regressed when low-fat and
cholesterol diets were resumed. In the 1970s and 1980s, findings from the landmark Framingham Heart, Seven Countries, and Multiple Risk Factor Intervention Trial studies firmly established that
hypercholesterolemia was a major risk factor for cardiovascular morbidity and mortality. During the 1980s and 1990s, 21 of 22 angiographic trials demonstrated reduced progression of coronary and/or
carotid artery disease using lifestyle,
drug, and surgical means for reducing
cholesterol. The later trials commonly employed hydroxymethylglutaryl
coenzyme A reductase inhibitors (
statins), reflecting increasing clinical use of these drugs. In 1988, the Adult Treatment Panel of the National
Cholesterol Education Program (NCEP) published guidelines on testing and treating hypercholesterolemic patients, which outlined a more aggressive approach to
cholesterol lowering than was currently in practice. Since 1994, five large cardiovascular event trials and a large angiographic trial have shown that aggressive
cholesterol lowering reduces both cardiac morbidity and mortality, largely substantiating the NCEP guidelines. Although important clinical questions remain regarding patient subsets and treatment goals, lifestyle changes and appropriate
drug therapy have proved to be highly effective in preventing initial and recurrent cardiovascular events.