FISH AND FISH OIL FOR PREVENTION OF CAD
See also under Ventricular Arrhythmias
Initial interest sprung from low rate of CAD in Greenland
Eskimos who eat lots of seal and fish; rich in
omega-3-polyunsaturated lipids
Animal studies have shown that intimal hyperplasia, an
intermediate step in atheroscleosis, can be decelerated with
cod-liver oil
Studies in humans have shown inconsistent results as of 1999
for either primary or secondary prevention
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)
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, RR of 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)
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)
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 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)
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)
Note--A synthetic preparation of omega-3-acid ethyl
esters is marketed as "Omacor" for treatment of hypertriglyceridemia
at a recommended dose of 4g divided QD-BID; shown to reduce TG and elevate HDL
in small randomized studies