Science, atherosclerosis and the "age of unreason": a review

Research in atherosclerosis has been dominated by the lipid hypothesis. The pathology of both the cholesterol-fed animal and of familial hypercholesterolemia has been misrepresented. The vascular lesions of these disorders are not atherosclerotic but manifestations of fat storage. There has been undue faith in the epidemiology of coronary heart disease and atherosclerosis. Fundamental defects in the epidemiological approach to the cause of atherosclerosis include: (1) misuse of cause and risk factors; (2) misuse of coronary heart disease as an imprecise and inappropriate surrogate endpoint in clinical and mortality studies; (3) use of fallacious monocausal death certificates and mortality rates; (4) assumed causal role of risk factors; (5) use of fallacious dietary data; (6) ecological fallacies; (7) nonspecificity of statistical correlations and selection bias; (8) failure to take note of inconsistencies; (9) inappropriate use of the blood cholesterol level as a surrogate of atherosclerosis (substitution game) without demonstration of any such effect on arteries; and (10) misplaced faith in pathological and experimental corroborative evidence. The epidemiology of atherosclerosis is based on unscientific methodology and the lipid hypothesis as currently envisaged is invalid. There is need to review the cholesterol-lowering campaign especially for normolipidemic subjects.