[Introduction]

It is well-known that plasma HDL-C shows a negative correlation with the incidence of coronary artery disease, which was confirmed by the Framingham Study, a famous prospective cohort study, in 1977. At first, HDL-C was determined by the precipitation method, and then the homogeneous method of HDL-C determination was developed in the 1990's in Japan. This method enabled HDL-C measurement in a short time for many samples. HDL removes free cholesterol from somatic cells by accepting cell cholesterol via ATP-binding cassette transporter A1. Cholesterol ester in HDL is transferred to VLDL and LDL by the action of cholesterol ester transfer protein or is incorporated into the liver via SR-BI. This pathway is called reverse cholesterol transport, which can regress atheromatous plaques. On the other hand, some CETP inhibitors, which can increase the HDL-C level have been developed in the world. However, the development of all candidate drugs was stopped because of side or insufficient effects. In addition, patients with CETP deficiency, whose HDL-C levels are markedly high, sometimes show the findings of coronary artery disease. These observations indicate that elevating HDL-C levels alone may not lower the cardiovascular disease risk. Recently, it was reported that HDL has pleiotropic functions other than reverse cholesterol transport. Actually, HDL inhibits lipid oxidation, impairs leukocyte adhesion and monocyte activation, promotes nitric oxide production, and inhibits the activation of platelets and the coagulation cascade. Functional characterization of HDL is, therefore, necessary for precise assessment of the cardiovascular risk and effectiveness of risk reduction.