A working group meeting was convened from January 7 to 8, 2000, in Naples, Florida, to assess low HDL cholesterol (HDL-C) concentration as a risk factor for coronary heart disease (CHD). The 30 speakers and discussants at this 2-day meeting included specialists in epidemiology, endocrinology, molecular biology, public health, lipid metabolism, cardiovascular medicine, and preventive cardiology from the United States, Europe, and Australia (Appendix). The group’s wide-ranging presentations and discussions considered the latest knowledge on HDL metabolism and the effects of interventions for raising HDL-C levels on the development of atherosclerosis. It was generally accepted that low HDL-C may be a marker for the metabolic syndrome, an enhanced atherosclerotic disease state that is also associated with an impaired response to insulin, hypertriglyceridemia, and abdominal obesity. Therefore, beyond risk assessment based on LDL cholesterol (LDL-C) alone, the case has been made for considering HDL-C in tandem with triglycerides (TG) as synergistic coronary risk factors.1 The following article summarizes the participants’ discussion of low HDL-C as an independent CHD risk factor and identifies areas requiring further research. Although population studies indicate that a high level of HDL-C in general protects against CHD,2 3 a high HDL-C concentration in any given individual may not necessarily confer cardioprotection. The atherogenicity of low HDL-C seems to be influenced by an array of genetic and environmental factors. Tangier disease, a disorder caused by mutations in the ATP-binding cassette transporter 1 ( ABC1 ) gene,4 is characterized by the absence of normal HDL, with only a very small quantity of abnormal HDL present. However, early atherosclerosis (before 40 years) is not a consistent feature of this disorder.5 In men of Japanese ancestry in Hawaii, mutations in the gene for plasma cholesteryl ester transfer protein ( CETP ), which transfers cholesteryl ester from HDL to TG-rich lipoproteins, have …
Read full abstract