Is Hypertriglyceridemia a Risk Factor for Atherosclerotic Cardiovascular Disease? A Simple Question with a Complicated Answer

The role of hypertriglyceridemia in the pathogenesis of atherosclerotic cardiovascular disease has been controversial for many years [1, 2]. It remains so despite extensive investigation by basic scientists, clinicians, and epidemiologists. The lack of resolution of this issue derives mainly from the complexity inherent in the lipoprotein transport system [3]. Although it is not possible to either unravel all of this complexity or resolve the controversy here, I attempt to provide a balanced review of the relevant literature, concluding with a suggested approach to the evaluation and treatment of the many patients who have elevated plasma triglyceride levels. I focus on the lipid aspects of this issue, but it should not be forgotten that elevated triglyceride levels have been associated with several abnormalities of the clotting-fibrinolytic systems [4].

Triglyceride does not accumulate in the vessel wall. Its atherogenicity must be based, therefore, on the association, within lipoproteins, between triglyceride and cholesterol, the lipid that does accumulate in atherosclerotic plaque. Thus, proponents of an association between hypertriglyceridemia and atherosclerotic cardiovascular disease must postulate that disordered metabolism of the triglyceride-rich lipoproteins-very low density lipoprotein (VLDL) or chylomicron or both-is proatherogenic. This concept is not extreme: Even the well-accepted link between cholesterol and atherosclerotic cardiovascular disease relies on the accumulation of low-density lipoprotein (LDL) cholesterol, not simply plasma cholesterol, in lesions. The concept that several lipoprotein species can contribute cholesterol to lesion formation is not, therefore, unreasonable. Indeed, ample studies have shown that chylomicron remnants (the lipoprotein formed from chylomicrons after removal of much, but not all, of the chylomicron triglyceride) and VLDL (or its remnants) enter the subendothelial space of the vessel wall [5, 6]. These lipoproteins can also be internalized by monocyte macrophages, resulting in formation of foam cells. Recent studies in transgenic mice dramatically demonstrated the …