In his November 1 editorial, Roberts persuasively summarized the line of evidence supporting serum cholesterol elevation as the essential cause of atherosclerosis and therefore as the dominant factor responsible for cardiovascular events. The editor then listed potential reasons why the role of cholesterol is frequently minimized. Chief among them is the emphasis on multiple atherosclerotic risk factors, which distracts from the proper clinical focus on cholesterol and potentially limits broader use of statin drugs. Roberts admonishes “to move on from a goal ‘to decrease risk’ to a goal ‘to prevent plaques.’ ”

A clear distinction between risk factor and disease is indeed essential to better identify and implement therapeutic goals, and rarely does published medical research articulate this dichotomy. Over the past 20 years, a number of risk factors have been elevated to the rank of disease solely on the basis of epidemiologic considerations. This departure from the traditional pathologic basis of disease has allowed expert committees to repeatedly revise the cut-off numbers that define “normality,” frequently generating confusion and controversy. Unless we can return to disease definitions rooted in clearly identifiable cellular or metabolic abnormalities, “stupidity” may continue to prevail.

Another impediment to a more rational use of statin drugs for the prevention and treatment of atherosclerosis must also be that early plaques cannot readily be visualized on clinical examination. It is therefore unfortunate that proposals to develop tools aimed at detecting and tracking early vascular lesions are met with strong opposition by those who favor the risk factor approach to disease prevention.

Finally, Roberts correctly states that “toxicity resides mainly in atherosclerosis, not in the drug.” However, harm from the disease is latent, as clinical manifestations may take years or decades to arise, if ever. With the drug, however, a major side effect is immediate and universal: the patient’s self-perception is altered forever, as he or she moves from a state of perceived health into the penumbra of an indistinct chronic condition named hypercholesterolemia. Some patients will agree to make this transition less readily than others, on the basis of cost-benefit calculations that are inherently subjective. Allowing patients and physicians to make individual informed choices should not be decried.