ABSTRACT
The relationship of lipids and lipoproteins to atherosclerosis is not a recent discovery. Nearly 100 years ago, Ignatowosky noted that wealthy patients who consumed large amounts of meat and dairy products appeared to have more arteriosclerosis on autopsy than poor patients who could not afford this rich type of food (1). Soon after this observation, Anitschkow and Chalatow conducted studies on rabbits that indicated that such high fat diets resulted in hypercholesterolemia and subsequent arteriosclerosis (2). With a tremendous amount of foresight, Aschoff suggested in 1924 that arteriosclerosis might be reversible (3). In the 1950s, Dr. John Gofman and colleagues at the Donner Laboratory (University of California) made another major step forward by investigating the relationship of low-density lipoproteins (LDL) to atherosclerosis in the Framingham and Lawrence Radiation Laboratory at Livermore studies (4). His contributions included the association of multiple lipoprotein subclasses defined by Svedberg floatation (Sf) intervals, assessed in the analytic ultracentrifuge. Gofman and colleagues were also well ahead of their time by reporting that high-density lipoprotein 2 (HDL2) (F3.5–9.0) was reduced 32.1% in patients who developed coronary artery disease (CAD). This raised the 36possibility of a protective role of HDL and HDL subclasses. An atherogenic index, based on these lipoprotein classes, attempted to quantitate the effect of these lipoproteins on atherosclerosis. With a great degree of prescience, which predated the Adult Treatment Panel guidelines by four decades, it was predicted that if longevity is linked to lipoproteins, then in order to improve longevity, “. a drastic rather than moderate reduction in such parameters is required.” Based on the work of Geer and McGill, it was even suggested that alteration in lipoprotein composition might lead to the development of atherosclerosis, even though no alteration in absolute lipoprotein levels occurred. Thus, the field of lipids, lipoproteins, and lipoprotein subclasses within the very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), LDL, and HDL regions, and their relationship to atherosclerosis, is at least 50 years old.
