General points

Population studies regarding fish consumption and cardiovascular disease:

  • Prospective population studies have shown lower risk of CAD among men and women with even low (1-2 servings/wk) dietary fish intake (RR 0.83 for coronary death with any amount of fish vs. little-or-no fish (sig.) in a meta-analysis of 19 cohort and case-control studies; Am. J. Cardiol. 93:1119, 2004--AFP)
  • US Physicians' Health Study looked prospectively at 20,000 men 40-84yo, free of MI, cerebrovascular disease, and Ca at baseline followed x 11y & incidence of sudden cardiac death; after controlling for age, ASA and beta-carotene use, and CAD risk factors, men who consumed fish 1 or more times per week had RR of sudden cardiac death of 0.48 (95% CI 0.24-0.96) c/w men who consumed fish less than Qmo; no sig. diff. with increasing intake. Also ass'd with decrease in total mortality (RR 0.70, 95% CI 0.55-0.89 for same comparison groups) (JAMA 279:23, 1997--abst)
  • Randomized studies of fish oil/omega-3 supplementation for mixed primary & secondary prevention of cardiovascular events:

  • In an open-label trial involving 18,645 pts with dyslipidemia randomized to eicosapentaenoic acid (EPA) 1.8g/d or no EPA in addition to statin therapy, over mean 4.6y f/u, incidence of the primary endpoint (major adverse coronary events), was sig. lower with combination than with statin therapy alone (2.8% vs. 3.5%); no sig. diff. in incidence of sudden death or coronary death. Difference in primary endpoint was sig. for subgroup who had prior h/o major coronary events (8.7% vs. 10.7%) but not for those with no such history ("JELIS" Trial; Lancet 369:1090, 2007--JW)
  • Randomized studies of fish oil/omega 3 supplementation for secondary prevention of cardiovascular events

  • 11,324 pts with MI in previous 3mos randomized to 1g/d of fish-oil, 300IU/d of vit. E, both, or neither. All were on antiplatelet agents, beta-blockers, and ACEIs. Over avg. 3.5y f/u, overall mortality was 9.2% in fish oil group c/w 11.4% in placebo group (sig.); addition of vit. E conferred no additional benefit (see Antioxidants for Prevention of CAD for that data) (Lancet 354:441, 1999--JW, AFP)
  • In a study in 4,837 pts with h/o MI in last 10y (86% were on lipid-lowering agents) randomized eicosapentaenoic acid/docosahexaeonic acid 400mg/d to alpha-linolenic acid 2g/d (both in a margarine substrate), both, or placebo, over median 40.8 mo f/u, incidence of incidence of (fatal or nonfatal cardiovascular disease, percutaneous coronary intervention, or CABG) was not sig. any of the groups ("Alpha Omega Trial"; NEJM 8/29/2010, e-pub ahead of printing; at:
  • Randomized studies of fish oil/omega-3 supplementation for prevention of progression of coronary stenoses:

  • 223 pts with coronary stenosis > 20% who had undergone or been scheduled for revascularization of one coronary artery were randomized to omega-3-fatty acids vs. placebo; after 2y, % of pts with increased luminal size in affected coronary artery was sig. higher in omega-3-fatty acid group, but overall comparisons of angiograms between groups did not show statistically sig. differences. Omega-3-fatty acid group had nonsig. fewer cardiovascular events than the placebo group (Ann. Int. Med. 130:554, 1999--JW)
  • Meta-analyses of both primary and secondary prevention studies:

  • In a Cochrane meta-analysis of 48 randomized studies (which combined primary and secondary prevention cases) involving over 30,000 patients, there was no sig. diff. in overall mortality, incidence of cardiovascular events, or incidence of cancer with use of either fish oil supplements (either with long-chain or short-chain omega-3 fatty acids) or instructions to eat more oily fish (BMJ 332:752, 2006--AFP)
  • In a meta-analysis of 12 randomized trials involving nearly 33,000 pts of fish oil supplements, fish oil use was associated with a sig. reduction in cardiac death (RR 0.8) but no sig. reduction in all-cause mortality (BMJ 338:a2931, 2008-JW)
  • In a meta-analysis in 20 randomized trials of omega-3-poly-unsaturated fatty acids vs. placebo involving 68,680 patients, there was no sig. diff. in incidence of all-cause mortality, cardiac death, sudden death, MI, or CVA (JAMA 308:1024, 2012-abst)
  • Note-Omega-3-fatty acid proparations have been approved for treatment of severe hypertriglyceridemia: