[High-density lipoprotein (HDL) and cholesteryl ester transfer protein (CETP): role in lipid metabolism and clinical meaning].

Large epidemiological studies have consistently shown that plasma levels of high-density lipoprotein (HDL) correlate inversely with cardiovascular risk. The apparent cardioprotective role of HDL has primarily been attributed to its participation in reverse cholesterol transport (RCT) but there is also substantial evidence that supports the concept of HDL and apoA-I preventing oxidative damage, inhibiting systemic inflammation, promoting vascular integrity and preventing thrombosis. Besides conventional therapy to increase HDL like physical exercise, weight loss and dietary changes new strategies to intervene at various steps of its metabolism have been proposed and are in development. One of the most promising approaches is inhibiting cholesteryl ester transfer protein (CETP)which plays a central role in RCT by transferring cholesteryl esters from HDL to apoB containing lipoproteins in exchange for triglycerides. The failure of the CETP inhibitor torcetrapib, however, to cause any benefit on cardiovascular outcomes despite significantly increased HDL levels in several clinical trials casted doubts upon the concept of CETP inhibition. Meanwhile, off target toxicity could be shown for torcetrapib and a new generation of CETP inhibitors stands ready to be tested in large clinical trials. This article describes the formation and remodeling of HDL, how HDL is thought to be beneficial for the vasculature and what options we have today to increase HDL levels with a special focus on CETP inhibition.