Is Hypertriglyceridemia always a Risk Factor?

The concept that hypertriglyceridemia is a risk factor for CHD has been disputed by epidemiological data that showed that an elevated plasma triglyceride concentration is not an independent risk factor of CHD. However, more insight in the heterogeneity of triglyceride-rich lipoproteins and the increased knowledge of lipoprotein metabolism have contributed to the growing notion that accumulation of cholesterol-rich VLDL and chylomicron remnants constitutes an atherogenic risk. An elevated plasma triglyceride concentration associated with obesity, low HDL-cholesterol concentration, dense small LDL particles, insulin resistance and prolonged postprandial lipemia bears a high risk of CHD. In the present chapter, we review the metabolic derangements of triglyceride-rich lipoproteins in hypertriglyceridemia. Endogenous hypertriglyceridemia is a multifactorial disease. Genetic as well as exogenous factors predispose subjects to the development of the characteristic lipoprotein abnormalities. Mutations in the LPL- and apoC-lll gene are important genetic factors, whereas increased amounts of visceral fat and insulin resistance are principal exogenous factors that contribute to the expression of hypertriglyceridemia. Several studies have demonstrated that overproduction of triglycerides and an impaired catabolism contribute to the hypertriglyceridemia. An increased supply of glucose and free fatty acids contributes to overproduction of very low density lipoproteins, thereby increasing the burden of triglyceride-rich lipoproteins on the common lipolytic pathway at the level of lipoprotein lipase. Low lipoprotein lipase activity and increased amounts of lipolysis- inhibiting free fatty acids further impair lipolysis. When dietary measures and hypoglycemic agents have failed to achieve acceptable lipid levels, lipid- lowering drugs should be advised. Fibric acids are the drugs of choice because of their significant improvement of lipid, lipoprotein and fibrinogen levels.