High Density Lipoproteins, Dyslipidemia, and Heart Disease: Past, Present, and Future

Abstract

The current focus of lipid management is on the treatment of elevated low density lipoprotein (LDL) cholesterol (>160 mg/dl) to decrease the risk of coronary heart disease (CHD), as well as less commonly to treat markedly elevated triglyceride levels (>1,000 mg/dl) to decrease the risk of pancreatitis. However, physicians and scientists have recognized that despite lifestyle and statin therapy, there is still a substantial residual risk of CHD, especially in patients with low high density lipoprotein (HDL) cholesterol levels (<40 mg/dl). In this atlas and book, the reader has been introduced to lipoprotein composition and metabolism, as well as lipid disorders. Thereafter, the focus has been on the regulation of apolipoprotein (apo) A-I gene expression, the composition of HDL particles, the modeling and metabolism of these particles, as well as HDL structure, function, and its anti-inflammatory properties. Next, we have provided the reader with information on disease states characterized by apoA-I deficiency, apoA-I variants, Tangier disease due to lack of ABCA1 function, the ABCG1 transporter, the interaction of HDL particles with transporters and receptors, human lecithin:cholesterol acyl transferase (LCAT) deficiency, human cholesteryl ester transfer protein (CETP deficiency, and the role of the scavenger receptor BI (SR-B1) in HDL metabolism. Thereafter, we provide the reader with information on the genetics of HDL in the general population, the role of nutrition, alcohol, and exercise in modulating HDL metabolism, and the effects of estrogens, niacin, statins, fibrates, CETP inhibitors, and HDL infusion therapy on HDL metabolism and coronary heart disease (CHD) risk reduction. Our goal in this concluding chapter is to focus on the current and future status of CHD risk assessment, the diagnosis and management of lipoprotein disorders, with a special focus on HDL. In our view, HDL raising is the next frontier in CHD risk reduction, and we will be using niacin products, CETP inhibitors, and HDL infusion therapy.