Effects of statins on high-density lipoproteins: a potential contribution to cardiovascular benefit.
OBJECTIVE
The objective was to systematically review clinical trial data on the effects of statins on high-density lipoproteins (HDL) and to examine the possibility that this provides cardiovascular benefits in addition to those derived from reductions in low-density lipoproteins (LDL).


METHODS
The PubMed database was searched for publications describing clinical trials of atorvastatin, pravastatin, rosuvastatin, and simvastatin. On the basis of predefined criteria, 103 were selected for review.


RESULTS
Compared with placebo, statins raise HDL, measured as HDL-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I); these elevations are maintained in the long-term. In hypercholesterolemia, HDL-C is raised by approximately 4% to 10%. The percentage changes are greater in patients with low baseline levels, including those with the common combination of high triglycerides (TG) and low HDL-C. These effects do not appear to be dose-related although there is evidence that, with the exception of atorvastatin, the changes in HDL-C are proportional to reductions in apo B-containing lipoproteins. The most likely explanation is a reduced rate of cholesteryl ester transfer protein (CETP)-mediated flow of cholesterol from HDL. There is some evidence that the statin effects on HDL reduce progression of atherosclerosis and risk of cardiovascular disease independently of reductions in LDL.


CONCLUSIONS
Statins cause modest increases in HDL-C and apo A-I probably mediated by reductions in CETP activity. It is plausible that such changes independently contribute to the cardiovascular benefits of the statin class but more studies are needed to further explore this possibility.
McTaggart
Fergus
F
Clinical Development, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. mctaggarts@aol.com
Jones
Peter
P
D016632:Apolipoprotein A-I / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D016896:Treatment Outcome
D016632:Apolipoprotein A-I; D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL