Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease

Epidemiologic and clinical studies suggest that elevated triglyceride levels are a biomarker of cardiovascular (CV) risk. Consistent with these findings, recent genetic evidence from mutational analyses, genome-wide association studies, and Mendelian randomization studies provide robust evidence that triglycerides and triglyceride-rich lipoproteins are in the causal pathway for atherosclerotic CV disease, indicating that they may play a pathogenic role, much like low-density lipoprotein cholesterol (LDL-C). Although statins are the cornerstone of dyslipidemia management, high triglyceride levels may persist in some patients despite statin therapy. Several triglyceride-lowering agents are available, including fibrates, niacin, and omega-3 fatty acids, of which prescription omega-3 fatty acids have the best tolerability and safety profile. In clinical studies, omega-3 fatty acids have been shown to reduce triglyceride levels, but products containing both eicosapentaenoic acid and docosahexaenoic acid may increase LDL-C levels. Icosapent ethyl, a high-purity eicosapentaenoic acid-only product, does not raise LDL-C levels and also reduces triglyceride, non-high-density lipoprotein cholesterol, and triglyceride-rich lipoprotein levels. In conclusion, omega-3 fatty acids are currently being evaluated in large CV outcome studies in statin-treated patients; these studies should help to elucidate the causative role of triglycerides in atherosclerotic CV disease.