hypertriglyceridemia

Triglycerides are transported in chylomicrons (dietary fat) and VLDL (endogenous synthesis in liver). Hypertriglyceridemia results from either overproduction of VLDL or impaired clearance of triglyceride-rich lipoproteins, often due to lipoprotein lipase (LPL) or apolipoprotein C-II deficiency/dysfunction. Primary causes include familial hypertriglyceridemia (type IV hyperlipoproteinemia, autosomal dominant), familial combined hyperlipidemia, and familial chylomicronemia syndrome (LPL or ApoC-II deficiency, type I), which presents in childhood with eruptive xanthomas, lipemia retinalis, and recurrent pancreatitis due to extremely high chylomicron levels. Secondary causes are more common clinically and include poorly controlled diabetes mellitus, obesity, excessive alcohol intake, hypothyroidism, nephrotic syndrome, pregnancy, and medications (thiazides, non-selective beta-blockers, estrogens, corticosteroids, protease inhibitors, tamoxifen). Clinically, hypertriglyceridemia is a well-established cause of acute pancreatitis when triglycerides exceed 1000 mg/dL, likely due to hydrolysis of triglycerides by pancreatic lipase generating free fatty acids that cause capillary injury and ischemia. It is also associated with increased risk of coronary artery disease, though the relationship is less direct than LDL cholesterol. Management includes lifestyle modification (diet, exercise, alcohol cessation, glycemic control) as first-line therapy. Pharmacologic options include fibrates (fenofibrate, gemfibrozil) as first-line for severe hypertriglyceridemia, omega-3 fatty acids, niacin, and statins for those with concurrent elevated LDL. Severe cases (>1000 mg/dL) may require urgent lowering to prevent pancreatitis, sometimes with insulin or plasmapheresis in acute settings.