Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease risk: current status and treatments

PURPOSE OF REVIEW: The role of triglyceride-rich lipoproteins (TRLs) in the development of atherosclerotic cardiovascular disease (ASCVD) is at the forefront of current research and treatment development programs. Despite extreme lowering of LDL-cholesterol there remains a high risk of cardiovascular disease and mortality. Recent large epidemiological, genomic wide association studies and Mendelian randomization studies have identified novel mechanisms and targets regulating TRL. This review will focus on recent and ongoing clinical trials that aim to reduce cardiovascular risk by decreasing plasma levels of TRL. RECENT FINDINGS: Ongoing efforts of basic and clinical scientist have described novel TRL regulating mechanism. The concentration on lifestyle changes is key to prevention and treatment guidelines. There is continue evidence that supports previous guidelines using fibrates alone and in combination with niacin to reduce TRLs, in special cases. The recent results from the REDUCE-IT study support the use of eicosapentaenoic acid (EPA) for risk reduction and ASCVD, but recently presented data from the Long-Term Outcome Study to Assess Statin Residual Risk Reduction With Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia and Omega-3 Fatty Acids in Elderly Patients With Acute Myocardial Infarction studies do not support the use of combination EPA/docosahexaenoic acid. The latter highlights the need for further studies into the pathways regulating ASCVD risk reduction after EPA administration. The identification of novel targets, such as apolipoprotein C3 and angiopoietin-like protein-3, are driving the development of novel treatments, and is the focus of this review. SUMMARY: The current management of elevated triglyceride levels and the effect on cardiovascular outcomes is an emerging area of research. New data from fish oil studies suggest differences in EPA vs. EPA/docosahexaenoic acid cardio protection outcomes. The preliminary data from ongoing clinical trials of novel triglyceride-lowering therapeutics are promising. These programs will ultimately provide foundations for future triglyceride-lowering guidelines.