New targets for medical treatment of lipid disorders.

Coronary heart disease (CHD) is the leading cause of death and disability in the industrialized world. Included among the risk factors for CHD are an elevated level of low-density lipoprotein (LDL) cholesterol and a low level of high-density lipoprotein (HDL) cholesterol. The discovery of drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), the rate-limiting enzyme in cholesterol biosynthesis, constituted a major advance in the treatment of patients with elevated plasma concentrations of LDL cholesterol. However, although the statins are potent LDL-lowering agents, they may not be the therapy of choice for all dyslipidemic patients. This is particularly true for subjects whose primary lipid abnormality is a low level of HDL cholesterol with or without hypertriglyceridemia, a group that includes about one half of patients with CHD. In this report, we review emerging options for the treatment of patients with lipid disorders, including inhibitors of cholesterol absorption, acyl coenzyme A-cholesterol acyltransferase, microsomal triglyceride transfer protein, and cholesteryl ester transfer protein, as well as liver X receptor agonists that up-regulate the expression of ATP-binding cassette transporter A1.