Small dense LDL: An emerging risk factor for cardiovascular disease.

Although low-density lipoprotein cholesterol (LDL-C) is a strong risk factor for coronary artery disease (CAD), LDL-C levels are not always elevated in CAD patients. LDL consists of several subclasses with distinct sizes, densities, and physicochemical compositions. Thus, LDL subclasses can be separated by various laboratory procedures. Among them, ultracentrifugation and electrophoresis have been used most frequently for determining LDL subclasses. Accumulating evidence has shown that a predominance of small dense LDL (sd-LDL) is closely associated with CAD. Moreover, sd-LDL-cholesterol (sd-LDL-C) concentrations are elevated in groups at a high risk for CAD, such as patients with type 2 diabetes and metabolic syndrome. Therefore, sd-LDL concentration is recognized as a surrogate marker for CAD. However, some studies failed to show therapeutic modulation of sd-LDL, likely because separating methods and sd-LDL particle definitions have not yet been standardized. Recently, a detergent-based homogenous assay for sd-LDL-C has been developed. This method does not require any pretreatment, and the measured values are highly reproducible with an automated analyzer. These features are suitable for large-scale clinical studies. This homogeneous assay is a useful tool for clarifying whether sd-LDL-C is a superior marker to LDL-C, and whether sd-LDL-C lipid-lowering therapies decrease the incidence of CAD.