title: History and future of omega-3 fatty acids in cardiovascular disease.
abstract: OBJECTIVE
  Epidemiological, diet-based, and some interventional outcomes studies suggest that polyunsaturated omega-3 fatty acids (OM3FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), confer cardiovascular protection in some patient populations. This review examines the historical context of OM3FAs in cardiovascular disease and future perspectives on the place of OM3FA products in reducing cardiovascular risk.
  
  
  METHODS
  Relevant articles were identified via PubMed/Medline and Google Scholar searches through 2015 and through reference lists of selected publications. Articles determined by the authors to be relevant to the topic of this review were included.
  
  
  RESULTS
  Review of the identified articles indicated that inconsistent results among interventional outcomes studies have been attributed to use of low doses of OM3FAs, patient cohorts with non-elevated triglyceride (TG) levels, differential use of concomitant statin therapy, and study designs with insufficient statistical power. Several prescription OM3FA products are now approved as an adjunct to diet to reduce TG levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. Most formulations contain both EPA and DHA; one formulation contains purified EPA. In randomized controlled trials, these products significantly reduced TG levels in patients with very high TG levels (≥500 mg/dL [≥13.0 mmol/L]) and in statin-treated patients with high TG levels (200-499 mg/dL [5.2-12.9 mmol/L]). The DHA-containing products raised LDL-C levels in these studies, whereas the EPA-only product had no effect on LDL-C, suggesting that all OM3FA prescription products are not therapeutically equivalent. Besides lowering TG levels, OM3FAs (particularly EPA) exert anti-inflammatory effects and may slow multiple atherogenic processes. Two well designed interventional outcomes studies (REDUCE-IT and STRENGTH) are evaluating prescription-strength, high-dose OM3FAs (4 g/day) in statin-treated patients with persistently high TG levels.
  
  
  CONCLUSIONS
  The results of the ongoing prescription-strength, high-dose OM3FA interventional trials will help define the potential role of OM3FAs in addressing residual cardiovascular risk despite statin therapy.
authors.affiliation: a a Emory University School of Medicine and Rollins School of Public Health at Emory University , Atlanta , GA , USA.
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Sperling
authors.affiliation: b b UCSF School of Medicine, Fresno-Medicine Residency Program-Volunteer , Fresno , CA , USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Nelson
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015228:Hypertriglyceridemia / Q000188:drug therapy; D012307:Risk Factors
chemical_list: D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: Atherosclerosis; Docosahexaenoic acid; Eicosapentaenoic acid; Omega-3 fatty acids; Triglycerides