title: Effect of drugs on high-density lipoprotein.
abstract: The National Cholesterol Education Program Adult Treatment Panel III found evidence for raising high-density lipoprotein cholesterol (HDL-C) to reduce coronary artery disease (CAD) events supports use of HDL-C to help modify low-density lipoprotein cholesterol (LDL-C)-lowering goals, but not to establish new HDL-C-focused treatment recommendations. However, the HDL-C-raising clinical trials provide important lessons to help guide clinical management of dyslipidemic patients. The fibrate outcome trials demonstrate that these drugs reduce CAD events, but not death. Their greatest benefit is in patients with atherogenic dyslipidemia characterized by high triglycerides, small LDL particles, and low HDL-C. Unfortunately, there is no information on whether these drugs extend risk reduction when added to a statin. The niacin outcome trials also demonstrate a reduction in CAD events, both with niacin monotherapy and in combination with a statin. Unfortunately, most of the trials are too small to address the impact of niacin on mortality. In the clinic, statins are most useful for their LDL-C-lowering efficacy, although their modest HDL-C-raising effects can be important in CAD risk reduction. In most cases, other therapies will need to be added to a statin to augment HDL-C-raising, and the most effective drug for achieving this is niacin. The greatest challenge with the use of niacin is managing the vasodilatory side effects, but this can be effectively done in the majority of patients. Fibrates can also be added to a statin for management of atherogenic dyslipidemia. These drugs are among the most effective triglyceride-lowering drugs, and they also increase HDL-C levels, but not as much as niacin. The biggest concern with combining a fibrate with a statin is the enhanced risk of severe muscle toxicity, but this appears to be a problem unique to gemfibrozil, and not fenofibrate. In the research center, new approaches are under development for enhancing the availability of apolipoprotein A-I (ApoA-I) and nascent HDL particles to promote enhanced reverse cholesterol transport, increasing the production of transport molecules, in particular, ATP-binding cassette A-I, to facilitate delivery of cholesterol within the macrophage cell to the cell surface, where it can be taken up by nascent HDL particles for transport to the liver, and inhibiting the cholesteryl ester transport protein to promote retention of cholesteryl esters within the HDL core for delivery back to the liver. In addition, new insights into the role of prostaglandin D(2) in the niacin flush and discovery of the niacin receptor has led to a search for a more efficacious and "flushless" niacin.
authors.affiliation: Virginia Commonwealth University and National Clinical Research, Inc, 2809 Emerywood Parkway, Suite 140, Richmond, VA 23294 USA.
authors.forename: James M
authors.initials: JM
authors.lastname: McKenney