High-density lipoprotein: a major risk factor for coronary atherosclerosis

Abstract

The high-density lipoproteins (HDL) are a polydisperse family of lipid--protein complexes whose principal functions in lipid transport are: (1) to act as a reservoir of C apoproteins required for triglyceride transport; (2) to act as a 'scavenger' of surplus cholesterol and phospholipid liberated from lipolysed triglyceride-rich lipoproteins; and (3) to transport surplus cholesterol from peripheral tissues to the liver for excretion and catabolism (reverse cholesterol transport), both directly and indirectly via other lipoproteins and the lipid transfer protein. The concentration of HDL cholesterol (mostly cholesteryl ester) has been found to be a strong risk factor for coronary atherosclerosis, and its clinical complications in most industrialized communities have been studied. The association with disease risk is independent of other lipoproteins and risk factors, has been found in both sexes, and persists following reduction of plasma lipids by diet and certain drugs. It is not yet clear whether or not certain HDL subclasses and/or apoproteins are better predictors of risk than HDL cholesterol. Indirect evidence from clinical studies and data from animal experiments suggests that certain pharmacologically induced increases in HDL cholesterol concentration are associated with a reduction of atherogenesis. However, the mechanism of the link between HDL and atherogenesis is not yet clear: although the original suggestion that it reflects the function of HDL in reverse cholesterol transport remains plausible, alternative mechanisms are possible. These include effects of HDL on platelet function and prostacyclin synthesis. Alternatively, the association might be indirect, reflecting an atherogenic effect of triglyceride-rich lipoproteins and/or their remnants, the plasma concentrations of which are correlated with HDL cholesterol.