Elevation of triglycerides (hypertriglyceridemia) is an independent risk factor for atherosclerosis-related cardiovascular disease. Similar to low-density lipoproteins (LDLs), triglyceride-rich lipoproteins (TRLs) accumulate in atherosclerotic plaques. Hypertriglyceridemia is associated with an overproduction of very low density lipoprotein (VLDL) particles or delayed catabolism of TRLs, their remnants, and apolipoprotein B (ApoB)–containing lipoproteins. (An apolipoprotein is a protein that combines with a lipid (fat) to form a lipoprotein.)

The delayed catabolism of TRLs and their remnants is a direct consequence of reduced lipoprotein lipase activities, hepatic (liver) remnant receptors, and increased apolipoprotein C-III (ApoC-III) levels. ApoC-III resides on a broad distribution of ApoB lipoproteins, including chylomicrons (very large lipoproteins rich in triglycerides, found in blood after the ingestion of fat), VLDLs, LDLs, and high-density lipoproteins (HDLs). It is the major regulator of lipolysis (the enzyme-catalyzed hydrolysis (removal) of fatty acids from triglycerides), noncompetitively inhibiting endothelial-bound lipoprotein lipase, which is the enzyme that hydrolyzes triacylglycerols in TRLs. ApoC-III can also inhibit hepatic lipase as well as the uptake of triacylglycerol-rich lipoprotein remnants by hepatic lipoprotein receptors. In addition, it has direct cellular effects that can contribute to cardiovascular disease.