Low levels of high-density lipoprotein cholesterol due to lecithin:cholesterol acyltransferase mutations increase carotid atherosclerosis.

Despite the long-held knowledge of an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and rates of cardiovascular disease (CVD) in populations, the HDL hypothesis has recently been shaken to its foundations by a barrage of controversial data. For example, clinical trials of an agent (torcetrapib) that increases HDL cholesterol by inhibiting cholesteryl ester transfer protein (CETP), an essential transferase that moves cholesterol from HDL to apolipoprotein B (apo B)– containing lipoproteins, have shown unexpected harm with increased cardiovascular events after 1 year of treatment among subjects who were already taking protective doses of atorvastatin (1). In addition, coronary and carotid imaging studies with the same agent failed to show vascular improvements attributable to the drug or to the increase in HDL cholesterol (2,3). Moreover, genetic studies have challenged