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Journal of Lipid Research, Vol. 46, 179-190, February 2005
Copyright © 2005 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 II: the early evidence linking hypercholesterolemia to coronary disease in humans¹

Daniel Steinberg²

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

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

The first in this series of historical reviews dealt with the pioneering animal model work of Anitschkow, implicating blood cholesterol in the pathogenesis of atherosclerosis, and the pivotally important work of Gofman, providing evidence that lipoprotein-bound cholesterol was a major factor in the human disease. This second installment reviews the early lines of evidence linking hypercholesterolemia in humans to the progression of atherosclerosis and the risk of coronary heart disease. The argument is made that by 1970, the evidence was already strong enough to justify intervention to lower blood cholesterol levels if all the available lines of evidence had been taken into account. Yet, it would be almost two decades before lowering blood cholesterol levels became a national public health goal.

Some of the reasons the "cholesterol controversy" continued in the face of powerful evidence supporting intervention are discussed.

Supplementary key words atherosclerosis • familial hypercholesterolemia • xanthomas • epidemiologic evidence • dietary fat • diet-heart clinical intervention studies

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