High-density lipoprotein therapeutics and cardiovascular prevention

The field of cardiovascular prevention has long anticipated the evolution of high-density lipoprotein (HDL) therapy from unproven metabolic tweaking to pillar of risk reduction on par with low-density lipoprotein control. However, the convincing epidemiologic data linking HDL cholesterol (HDL-C) and cardiovascular disease risk in an inverse correlation has not yet translated into clinical trial evidence supporting linearity between HDL-C increases and risk reduction, or identifying obvious goals of therapy. Although HDL-C-increasing lifestyle maneuvers and established HDL drugs such as niacin and fibrates are likely to protect the vasculature, the negative results obtained in trials of a cholesteryl ester transfer protein inhibitor remind us that HDL-C increases are not always beneficial. It is becoming clear that a functional HDL is a more desirable target than simply increasing HDL-C levels. The larger objective of improving HDL functionality (with or without HDL-C level changes) is bound to become the guiding principle for pharmaceutical research in this area. Several new compounds currently being tested bridge the classical aim of increasing HDL-C levels with the novel target of improving HDL function.