Effects of statins on high-density lipoproteins: a potential contribution to cardiovascular benefit

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.

Fig. 1

Effects of statins on a high-density lipoprotein cholesterol (HDL-C) and b apolipoprotein A-I (apo A-I) in placebo-controlled studies in hypercholesterolemic patients. Data are shown as mean percent change from baseline ±95% confidence limits. Dose (mg) is shown at the foot of each column

Fig. 2

Effects of statins given at recommended start doses on a high-density lipoprotein cholesterol (HDL-C) and b apolipoprotein A-I (apo A-I) in hypercholesterolemic patients. Data are shown as mean percent change from baseline ±95% confidence limits when available. Number at the base of the columns refers to the study as indicated in the table

Fig. 3

Dose-related effects of statins on a high-density lipoprotein cholesterol (HDL-C) and b apolipoprotein A-I (apo A-I) in hypercholesterolemic patients in five studies. Data are shown as mean percent change from baseline ±95% confidence limits when available. Dose (mg) is shown at the base of each column

Fig. 4

Relationships between mean percent changes in high-density lipoprotein cholesterol (HDL-C) and mean percent changes in a triglycerides (TG) and b low-density lipoprotein cholesterol (LDL-C) in the STELLAR study [72]. Dashed lines calculated by a robust MM estimation. Panel a taken from Jones et al. [114]

Fig. 5

Effects of statins at the maximal clinical doses on a high-density lipoprotein cholesterol (HDL-C) and b apolipoprotein A-I (apo A-I) in hypercholesterolemic patients. Data shown as mean percent change from baseline ±95% confidence limits when available. Dose (mg) is shown given at the foot of each column