Epidemiologic and clinical studies have demonstrated a relation between plasma
triglyceride levels and risk of
coronary artery disease and an amplification of risk with combined elevations of
triglyceride and
low-density lipoprotein (
LDL) cholesterol. In patients with
coronary disease, angiographic progression and clinical events have been correlated with concentrations of smaller
very-low-density lipoproteins (VLDL) and
intermediate-density lipoproteins (IDL), consistent with evidence for enhanced atherogenicity of lipolytic products of
triglyceride-rich
lipoprotein metabolism, including postprandial
lipoproteins. IDL levels also have been shown to be strongly and independently predictive of progression of carotid artery intimal-medial thickness, a measure of early
atherogenesis that is related to
coronary disease risk. Although there is evidence that these
triglyceride-rich
lipoprotein species may have direct atherogenic effects, other
lipoprotein changes associated with altered
triglyceride metabolism may be of particular importance in the development of
coronary artery disease. These include reductions in
high-density lipoprotein (HDL) and increases in small, dense
LDL particles (
LDL subclass pattern B). Because of the strong interrelations among elevated
triglyceride, reduced HDL, and small dense
LDL, it is difficult to use statistical techniques to determine the independent contributions of these traits to
coronary disease risk. Based on their
biologic properties, it is likely that each are involved in multiple steps of the disease process. Moreover, this cluster of
lipoprotein changes is associated with other conditions that can promote
vascular disease, including increases in
coagulation factors and reduced
insulin sensitivity. Analyses from intervention trials in patients with
coronary disease have indicated that measurement of plasma
triglyceride and
LDL particle distributions can be of value in predicting the benefits of specific
lipid-altering
therapies on
disease progression.