Cardioprotective Effects of High-Density Lipoproteins

Abstract

The fact that a low level of high-density lipoprotein (HDL) cholesterol is highly predictive of future cardiovascular events has been established in population studies beyond all reasonable doubt. Furthermore, the evidence is overwhelming that the relationship is one of cause and effect rather than an epiphenomenon, with numerous studies in animals demonstrating that HDL-raising interventions translate into profound reductions in atherosclerosis. Such interventions have included the infusion of both native and reconstituted HDLs into rabbit models of atherosclerosis, the overexpression of apolipoprotein (apo) A-I (the major HDL protein) in transgenic mice and rabbits, and the inhibition of cholesteryl ester transfer protein (CETP) in rabbits. See pages 1325 and 1426 Evidence that raising the level of HDLs is also antiatherogenic in humans is mounting, although there are still relatively few human studies that have directly tested the phenomenon. Fibrates, statins, and niacin all raise the level of HDL cholesterol, and treatment with each of these agents has been shown to be associated with a reduction in future cardiovascular events. Fibrates are especially effective in event reduction in people with insulin resistance or with other features of the metabolic syndrome, although the benefits cannot be explained in terms of the observed HDL raising.1 Statins are effective in reducing events in all subjects, but the benefits can be explained almost completely in terms of the achieved LDL lowering2; the contribution of a statin-induced elevation of HDL is difficult to evaluate. Niacin, the most effective of the currently available HDL-raising agents, has also been shown to reduce cardiovascular events, especially when coadministered with a statin3; but again, other properties of niacin may …