HDL-C: does it matter? An update on novel HDL-directed pharmaco-therapeutic strategies.
It has long been recognized that elevated levels of low-density lipoprotein cholesterol (LDL-C) increase the risk of cardiovascular disease (CHD) and that pharmacologic therapy to decrease LDL-C significantly reduces cardiovascular events. Despite the effectiveness of statins for CHD risk reduction, even optimal LDL-lowering therapy alone fails to avert 60% to 70% of CHD cases. A low plasma concentration of high-density lipoprotein cholesterol (HDL-C) is also associated with increased risk of CHD. However, the convincing epidemiologic data linking HDL cholesterol (HDL-C) to CHD risk in an inverse correlation has not yet translated into clinical trial evidence supporting linearity between HDL-C increases and CHD risk reduction. It is becoming clear that a functional HDL is a more desirable target than simply increasing HDL-C levels. Discoveries in the past decade have shed light on the complex metabolic and antiatherosclerotic pathways of HDL. These insights, in turn, have fueled the development of new HDL-targeted drugs, which can be classified according to four different therapeutic approaches: directly augmenting the concentration of apolipoprotein A-I (apo A-I), the major protein constituent of HDL; indirectly augmenting the concentration of apo A-I and HDL cholesterol; mimicking the functionality of apo A-I and enhancing reverse cholesterol transport. This review discusses the latest in novel HDL directed therapeutic strategies.
Einstein Institute for Heart and Vascular Health, Albert Einstein Medical Center, and Jefferson Medical College, PA 19141, United States. ram.gadi@gmail.com
Ramprasad
R
Gadi
Aman
A
Amanullah
Vincent M
VM
Figueredo
D017668:Age of Onset; D000818:Animals; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D009525:Niacin / Q000627:therapeutic use; D012307:Risk Factors; D040242:Risk Reduction Behavior
D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009525:Niacin