Statins, inhibitors of the key enzyme in the endogenous synthesis of cholesterol (3-hydroxy-3-methylglutaryl coenzyme A reductase, or HMG-CoA reductase) have been proven to be very effective in lowering plasma LDL-C levels and significantly reduce the risk of coronary heart disease. Statins also modestly increase plasma levels of HDL-C. The mechanism of the effect of statins on apo A-I metabolism has been studied by several groups. The current literature shows no significant effects of atorvastatin on plasma apo A-I concentrations and apo A-I kinetics, but a significant reduction of both production and clearance of apo A-I with rosuvastatin, without significant changes in plasma apo A-I concentrations. It is thought that the reduction in HDL clearance with rosuvastatin is due to the statin-associated reduction in plasma TG-rich lipoproteins levels, which leads to a reduction in the substrate for cholesteryl ester transfer protein (CETP), and therefore to a reduction in the TG content and increase in cholesterol content of HDL. These results contrast with findings of increased apo A-I expression and production by statins in vitro.