Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men

Background - Consumption of polyunsaturated fatty acids (PUFAs) may reduce coronary heart disease (CHD) risk, but n-6 PUFAs may compete with n-3 PUFA metabolism and attenuate benefits. Additionally, seafood-based, long-chain n-3 PUFAs may modify the effects of plant-based, intermediate-chain n-3 PUFAs. However, the interactions of these PUFAs in relation to CHD risk are not well established. Methods and Results - Among 45 722 men free of known cardiovascular disease in 1986, usual dietary intake was assessed at baseline and every 4 years by using validated food-frequency questionnaires. CHD incidence was prospectively ascertained. Over 14 years of follow-up, participants experienced 218 sudden deaths, 1521 nonfatal myocardial infarctions (MIs), and 2306 total CHD events ( combined sudden death, other CHD deaths, and nonfatal MI). In multivariate-adjusted analyses, both long-chain and intermediate-chain n-3 PUFA intakes were associated with lower CHD risk, without modification by n-6 PUFA intake. For example, men with greater than or equal to median long-chain n-3 PUFA intake ( greater than or equal to 250 mg/d) had a reduced risk of sudden death whether n-6 PUFA intake was below ( < 11.2 g/d; hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.34 to 0.79) or above ( >= 11.2 gd; HR = 0.60; 95% CI = 0.39 to 0.93) the median compared with men with a < median intake of both. In similar analyses, greater than or equal to median intake of intermediate-chain n-3 PUFAs ( greater than or equal to 1080 mg/d) was associated with a reduced total CHD risk whether n-6 PUFA intake was lower (HR = 0.88; 95% CI = 0.78 to 0.99) or higher (HR = 0.89; 95% CI = 0.79 to 0.99) compared with a < median intake of both. Intermediate-chain n-3 PUFAs were particularly associated with CHD risk when long-chain n-3 PUFA intake was very low ( < 100 mg/d); among these men, each 1 g/d of intermediate-chain n-3 PUFA intake was associated with an approximate to 50% lower risk of nonfatal MI ( HR = 0.42; 95% CI = 0.23 to 0.75) and total CHD ( HR = 0.53; 95% CI = 0.34 to 0.83). Conclusions - n-3 PUFAs from both seafood and plant sources may reduce CHD risk, with little apparent influence from background n-6 PUFA intake. Plant-based n-3 PUFAs may particularly reduce CHD risk when seafood-based n-3 PUFA intake is low, which has implications for populations with low consumption or availability of fatty fish.