HDL biology
Review attributes statins' modest HDL-raising effect to reduced CETP-mediated cholesterol flow (Cardiovasc Drugs Ther 2008)
Original title: Effects of statins on high-density lipoproteins: a potential contribution to cardiovascular benefit
This systematic review of 103 clinical trials of atorvastatin, pravastatin, rosuvastatin, and simvastatin found that statins consistently raise HDL-cholesterol and apolipoprotein A-I compared with placebo, with HDL-C rising approximately 4% to 10% in hypercholesterolemia and larger gains in patients with low baseline HDL-C and high triglycerides. These HDL effects were not dose-related, though outside atorvastatin they were proportional to reductions in apoB-containing lipoproteins, and the review concludes the most likely explanation is a reduced rate of CETP-mediated cholesterol flow from HDL. The authors conclude statins' modest HDL and apoA-I increases are probably mediated by reduced CETP activity, and that this may independently contribute to statins' cardiovascular benefit beyond LDL lowering.
Original abstract
Purpose: 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.
Conclusion: 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.