Mechanisms of Disease: HDL metabolism as a target for novel therapies

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Abstract
Despite aggressive lipid-lowering therapy, coronary heart disease event rates remain unacceptably high, indicating the need for additional therapeutic approaches. Notably, low HDL-cholesterol levels remain an independent risk factor for adverse coronary events even in patients with naturally low or therapeutically lowered LDL-cholesterol levels. Here, Daniel Rader examines the current status of the development of novel therapies aimed at raising HDL-cholesterol levels or improving the function of HDL. Plasma concentrations of HDL cholesterol are inversely correlated with risk of coronary heart disease, and low HDL-cholesterol levels are a risk factor even in patients aggressively treated for LDL reduction. Thus, there is great interest in targeting HDL cholesterol therapeutically. The existing approaches are limited in their ability to raise HDL-cholesterol levels, and there has, therefore, been a major focus on the development of novel therapies. The goal of new approaches is to either raise HDL-cholesterol levels or improve the function of HDL. Here, the current status of the development of novel therapies targeted toward HDL metabolism is reviewed.

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