Review traces how statins raise HDL cholesterol partly via a secondary reduction in CETP activity (Curr Atheroscler Rep 2006)

Statins inhibit cholesterol synthesis and are effective in lowering total cholesterol levels in plasma or serum due to reductions in low-density lipoprotein and very low-density lipoproteins, as well as reducing progression of coronary atherosclerosis, coronary heart disease, and stroke morbidity and mortality. These agents also modestly raise levels of high-density lipoprotein (HDL) cholesterol and its major protein, apolipoprotein (apo) A-I. The more effective statins can also raise the levels of large alpha-1 HDL particles as assessed by two-dimensional gel electrophoresis. High levels of these particles promote reverse cholesterol transport and protect against coronary heart disease and progression of coronary atherosclerosis. The mechanism whereby statins alter HDL and its subspecies appears to be due to reduction of triglyceride-rich lipoproteins, with a secondary decrease in cholesteryl ester transfer protein activity, and less transfer of HDL cholesterol to triglyceride-rich lipoprotein acceptor particles. Increasingly, statins will be combined with other agents such as ezetimibe, fibrates, niacin, and cholesteryl ester transfer protein inhibitors to optimize the entire lipoprotein profile to alter not only low-density lipoprotein, but also HDL, triglycerides, lipoprotein(a), and C-reactive protein, and also to reduce cardiovascular morbidity and mortality.