Introduction of HDL Molecules, Past and Brief Future

Abstract Our understanding of high-density lipoprotein cholesterol (HDL-C) and its relationship to coronary heart disease (CHD) has changed dramatically over the past half century. The initial discovery of the protective role of HDL-C was made by Gofman in the mid-1950s. In the mid-1970s, Glomset’s pioneering studies on reverse cholesterol transport (RCT) and Gordon’s Framingham study supported the concept that HDL-C was a “good” lipoprotein, since there was a strong inverse correlation between the levels of serum HDL-C and the subsequent risk of atherosclerosis. Furthermore, in the late-1980s, a decreased concentration of serum HDL-C emerged as one of the major risk factors for coronary artery disease. However, recent studies in the early 2000s have shown that high HDL-C levels do not necessarily have anti-atherogenic effects. In patients with cholesterol ester transfer protein (CETP) deficiency, high HDL-C levels have no anti-atherogenic effect. Furthermore, drugs that inhibit CETP elevate HDL-C levels but do not decrease the risk of cardiac events. Thus, the traditional anti-atherogenic role of HDL-C has been questioned. There is evidence that HDL-C molecules have additional atheroprotective roles beyond bulk cholesterol removal from cells through RCT. Other studies suggest that the widely used diagnostic measurement of HDL-C may have a limitation and that the qualitative measurement of HDL-C molecules may be important in the near future.