Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Implications for treatment.

Hypertriglyceridemia is commonly found in patients with coronary heart disease. The reason for this connection, however, is not well understood, and two different views have been put forth to explain the link. First, triglyceride-rich lipoproteins, particularly very-low-density lipoproteins, may be directly atherogenic. Or second, the metabolic consequences of hypertriglyceridemia may account for the triglyceride-coronary heart disease relationship. These consequences include an increase in postprandial lipoproteins, large very-low-density lipoprotein particles, small, dense low-density lipoprotein particles, low levels of high-density lipoprotein cholesterol, and possibly a procoagulant state. The appropriate treatment of hypertriglyceridemia depends on which of these views is nearer the truth. If triglyceride-rich lipoproteins are directly atherogenic, then the preferred therapy would be hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors, which lower both very-low-density lipoprotein and low-density lipoprotein levels. On the other hand, if the link to atherogenesis is through the metabolic consequences of hypertriglyceridemia, the appropriate therapy would be to directly lower serum triglyceride levels, as with niacin or a fibric acid. Thus, discovery of the mechanism of the connection between triglycerides and coronary heart disease is crucial for developing a rational therapy.