BACKGROUND:Aortocoronary vein bypass grafts are vulnerable to late atherosclerotic occlusion. Conventional platelet inhibitor therapy provides early but not persistent protection against graft failure. Evidence suggests that consumption of marine foods may reduce cardiovascular disease, possibly because of the unique long-chain unsaturated omega-3 fatty acids present in these foods. We hypothesized that dietary fish-oil supplementation would protect against atherosclerosis in vein bypass grafts. METHODS AND RESULTS:Thirty-three moderately hypercholesterolemic cynomolgus macaques were divided into four groups: control, control+aspirin, fish oil, and fish oil+aspirin. Each control group received olive oil as placebo to equalize calorie and fat consumption with that of the fish-oil groups. Both oils were in ethyl ester form, with the fish oil providing 0.88 g/d eicosapentaenoic acid. The aspirin dose was 40 mg/d. Cephalic vein grafts were interposed bilaterally in the carotid arteries and excised for analysis at 4 years. Bleeding time was significantly prolonged in all groups receiving fish oil or aspirin (P<.05). Plasma cholesterol levels were similar among groups, averaging 6.9+/-2.4 mmol/L (267+/-94 mg/dL). The extent of atherosclerosis in vein grafts did not differ among groups as evaluated both by Sudan IV staining of intimal lipid lesions (27+/-21% of total surface area, P=.89) and analysis of cholesterol content (236+/-203 nmol/mg, 9.1+/-7.8 microg/mg, P=.85). Vein graft connective tissue composition was also unaffected by treatment. CONCLUSIONS: Our findings do not support the use of concentrated dietary fish-oil supplements or aspirin for the prevention of atherosclerosis in long-term vein bypass grafts. Consumption of fish flesh or less refined oil preparations could have effects different from those of the purified fish-oil ethyl esters we used.
RCT Entities:
BACKGROUND: Aortocoronary vein bypass grafts are vulnerable to late atherosclerotic occlusion. Conventional platelet inhibitor therapy provides early but not persistent protection against graft failure. Evidence suggests that consumption of marine foods may reduce cardiovascular disease, possibly because of the unique long-chain unsaturated omega-3 fatty acids present in these foods. We hypothesized that dietary fish-oil supplementation would protect against atherosclerosis in vein bypass grafts. METHODS AND RESULTS: Thirty-three moderately hypercholesterolemic cynomolgus macaques were divided into four groups: control, control+aspirin, fish oil, and fish oil+aspirin. Each control group received oliveoil as placebo to equalize calorie and fat consumption with that of the fish-oil groups. Both oils were in ethyl ester form, with the fish oil providing 0.88 g/d eicosapentaenoic acid. The aspirin dose was 40 mg/d. Cephalic vein grafts were interposed bilaterally in the carotid arteries and excised for analysis at 4 years. Bleeding time was significantly prolonged in all groups receiving fish oil or aspirin (P<.05). Plasma cholesterol levels were similar among groups, averaging 6.9+/-2.4 mmol/L (267+/-94 mg/dL). The extent of atherosclerosis in vein grafts did not differ among groups as evaluated both by Sudan IV staining of intimal lipid lesions (27+/-21% of total surface area, P=.89) and analysis of cholesterol content (236+/-203 nmol/mg, 9.1+/-7.8 microg/mg, P=.85). Vein graft connective tissue composition was also unaffected by treatment. CONCLUSIONS: Our findings do not support the use of concentrated dietary fish-oil supplements or aspirin for the prevention of atherosclerosis in long-term vein bypass grafts. Consumption of fish flesh or less refined oil preparations could have effects different from those of the purified fish-oilethyl esters we used.