Hypertriglyceridemia: Causes, Consequences, Diagnosis, and Management

Managing hypertriglyceridemia (HTG) requires more than lowering triglyceride (TG) levels. Two related but clinically distinct risk domains often guide management: residual atherosclerotic cardiovascular disease (ASCVD) risk and acute pancreatitis (AP) risk. Their relative importance varies among patients and may change over time. Residual ASCVD risk is driven in part by the burden of atherogenic apolipoprotein B (apoB)-containing particles, particularly TG-rich lipoproteins and their cholesterol-enriched remnants, whereas AP risk increases with severe HTG and rises further in extreme HTG, in which chylomicron accumulation, free fatty acid-mediated lipotoxicity, and inflammation contribute to pancreatic injury. Because similar TG values can arise from different combinations of genetic susceptibility, metabolic dysfunction, and other secondary factors, TG alone may not fully characterize clinical risk or provide a sufficient basis for treatment selection. In this review, we examine the genetic and metabolic determinants of HTG and consider how TG, apoB, remnant cholesterol, chylomicronemia, and secondary causes can be integrated into clinical assessment. We also evaluate established treatments and emerging therapies targeting apolipoprotein C-III, angiopoietin-like protein 3, and related pathways. This risk-based framework can help clinicians tailor treatment to each patient's ASCVD and pancreatitis risk profile.