High-Density Lipoprotein Cholesterol, Plasma Triglyceride, and Coronary Heart Disease: Pathophysiology and Management

Compared with the relation between coronary heart disease (CHD) and its most important risk factor, hypercholesterolemia, the relation between CHD and fasting triglyceride levels is undoubtedly more complex biologically and statistically. This chapter reviews clinically relevant disturbances in the metabolism of triglyceride-rich lipoproteins and high-density lipoprotein (HDL), discusses the evidence linking the metabolism of triglyceride-rich lipoproteins to HDL cholesterol levels and CHD, and describes treatments to correct these disorders. In human, lipoproteins are produced by the intestine and liver. Lipoprotein biosynthesis is a highly specialized process that includes the synthesis of apolipoproteins and lipids, cellular transport of lipoprotein components, and their intracellular assembly and secretion into blood or lymph. Lipoproteins undergo postsecretory processing in the circulation and are eventually removed from the circulation. Exogenous and endogenous lipid transport pathways are distinguished according to lipid origin, even though these pathways overlap extensively. In the plasma, HDL exists as several subfractions that differ in physicochemical and functional properties. Several of these subfractions can be interconverted in the circulation, a process linked to the metabolism of triglyceride rich lipoproteins and involving various lipoprotein-modifying enzymes such as lipoprotein lipase (LPL), Lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and hepatic lipase. CETP-mediated transfer of triglyceride from triglyceride-rich lipoproteins to HDL in exchange for cholesteryl ester is central to the inverse relation between plasma triglyceride and HDL cholesterol. Immunological blockage of CETP increases the cholesteryl ester content of HDL and delays HDL clearance from the circulation. The inverse association between plasma triglyceride and HDL cholesterol breaks down in inherited CETP deficiency, in which HDL cholesterol levels are high irrespective of plasma triglyceride concentrations.