The Importance of Hypertriglyceridemia: Risk of Atherosclerosis and Available Treatments

Abstract

Serum triglycerides are derived from both exogenous and endogenous sources. Exogenous triglycerides are obtained through the diet and circulate post prandially within large, intestinally-derived chylomicron particles, which are normally cleared within 3 to 4 hours after eating. Endogenous triglycerides are hepatically produced and circulate in smaller very low density lipoprotein (VLDL) particles, which are remodelled in plasma to form even smaller triglyceride-depleted low density lipoprotein (LDL) particles.  While the atherogenic impact of LDL and its cholesterol content are well appreciated, the atherogenic role of triglyceride-rich lipoprotein particles, including VLDL and various remnant lipoprotein species, had only recently come into focus.

Approximately 25% of the population has mild-to-moderate hypertriglyceridemia, characterized by triglyceride levels ranging from 2 to 9.9 mmol/L, while approximately 1 in 500 has severe hypertriglyceridemia, defined as triglyceride levels >10 mmol/L. Pathogenic DNA variants within the gene encoding the triglyceride clearing enzyme lipoprotein lipase (LPL) or one of its co-factors (APOC2, APOA5, GPIHBP1 or LMF1) can cause severe hypertriglyceridemia, that presents in childhood. Adults with milder forms of genetic predisposition in combination with secondary factors, can also express triglyceride levels this high.