LIPIDS: Edited by Dan StrejaTriglycerides and residual riskVallejo-Vaz, Antonio J.a; Corral, Pablob; Schreier, Laurac; Ray, Kausik K.aAuthor Information aImperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK bPharmacology Department, School of Medicine, FASTA University, Mar del Plata cDepartamento de Bioquímica Clínica, Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Laboratorio de Lípidos y Aterosclerosis, INFIBIOC-UBA, Buenos Aires, Argentina Correspondence to Dr Antonio J. Vallejo-Vaz, MD, PhD, Department of Primary Care and Public Health, Imperial College Charing Cross Campus, St Dunstan's Road, W6 8RP London, UK. E-mail: [email protected] Current Opinion in Endocrinology & Diabetes and Obesity: April 2020 - Volume 27 - Issue 2 - p 95-103 doi: 10.1097/MED.0000000000000530 Buy Metrics Abstract Purpose of review To review the recent evidence from observational/genetic/interventional studies addressing triglycerides and residual cardiovascular risk (CVRisk). Recent findings Large population-based and secondary prevention studies consistently show an association of higher triglycerides with increased CVRisk. This is compounded by genetic studies demonstrating an independent relationship between triglyceride raising or lowering genetic variants affecting triglyceride-rich lipoproteins (TRL) metabolism and CVRisk. Mendelian randomization analysis suggests the benefit of genetic lowering of triglycerides and LDL-cholesterol is similar per unit change in apolipoprotein-B. Among cholesterol-lowering trials, more intensive statin therapy produced greater CVRisk reductions in patients with higher TRL-cholesterol or triglycerides; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition led to similar triglycerides reduction but greater non-HDL-C or apolipoprotein-B reductions than fibrates or fish oils. Regarding n-3 fatty acids, A Study of Cardiovascular Events in Diabetes (ASCEND) and Vitamin D and Omega-3 Trial (VITAL) primary prevention trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid failed to demonstrate cardiovascular benefits, Conversely, Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) using high-dose icosapent-ethyl (purified EPA) in primary (diabetes) and secondary prevention with hypertriglyceridemia showed significant cardiovascular events reductions (greater than expected by the observed triglycerides or apolipoprotein-B reductions, suggesting potential benefits through non-lipid pathways). Summary Evidence suggests higher triglycerides are a marker of CVRisk and may help identify patients who benefit from intensification of therapy. Moreover, genetic studies support a causal link between TRL/triglycerides and cardiovascular disease. Treatment with high-dose EPA may be of benefit in high-risk patients with hypertriglyceridemia to reduce CVRisk. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.