Abstract

High-density lipoprotein cholesterol levels have a strong inverse association with a risk of cardiovascular disease. Even patients on statin therapy whose low-density lipoprotein cholesterol levels are well controlled may be at high risk for developing cardiovascular disease if their high-density lipoprotein cholesterol levels are below 40 mg/dl. Consequently, current guidelines recognize low levels of high-density lipoprotein cholesterol as a major risk factor and suggest that treatment should be considered for isolated low level of high-density lipoprotein cholesterol. Unfortunately, only a few therapies are particularly effective at increasing high-density lipoprotein cholesterol, one promising new approach targets cholesteryl ester transfer protein. In healthy subjects with mild dyslipidemia, treatment with JTT-705 decreased cholesteryl ester transfer protein activity, increased high-density lipoprotein cholesterol and decreased low-density lipoprotein cholesterol. Similarly, another cholesteryl ester transfer protein inhibitor, torcetrapib, has recently been shown to increase high-density lipoprotein cholesterol by 46%. Increasing high-density lipoprotein cholesterol with inhibitors of cholesteryl ester transfer protein represents a new approach to dyslipidemia that requires further investigation, especially in patients with coronary artery diseases. The goal of this review is therefore to discuss the potential clinical relevance of cholesteryl ester transfer protein inhibition in hyperlipidemic subjects at elevated cardiovascular risk.