title: A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.
abstract: OBJECTIVE
  To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk.
  
  
  METHODS
  A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed.
  
  
  RESULTS
  Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event.
  
  
  CONCLUSIONS
  Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.
authors.affiliation: Department of Epidemiology, EpidStat Institute, Ann Arbor, MI. Electronic address: dalexander@epidstat.com.
authors.forename: Dominik D
authors.initials: DD
authors.lastname: Alexander
authors.affiliation: Nutrition and Food Services, Edward Hines Jr VA Hospital, Hines, IL.
authors.forename: Paige E
authors.initials: PE
authors.lastname: Miller
authors.affiliation: Scientific and Regulatory Affairs, Van Elswyk Consulting, Inc, Longmont, CO.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Van Elswyk
authors.affiliation: Scientific Affairs, Kuratko Nutrition Research, Ellicott City, MD.
authors.forename: Connye N
authors.initials: CN
authors.lastname: Kuratko
authors.affiliation: Department of Epidemiology, EpidStat Institute, Ann Arbor, MI.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Bylsma
mesh_terms: D003327:Coronary Disease / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
chemical_list: D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid