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.
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Atherosclerosis Research Unit, 383 PRB-2220 Pierce Avenue, Nashville, TN 37232-6300, USA. sergio.fazio@vanderbilt.edu
Sergio
S
Fazio
Macrae F
MF
Linton
D016632:Apolipoprotein A-I / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D002986:Clinical Trials as Topic; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D011341:Probucol / Q000627:therapeutic use
D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D011341:Probucol