High long-chain n-3 fatty acid intake attenuates the effect of high resting heart rate on cardiovascular mortality risk: A 24-year follow-up of Japanese general population

Background: Increased resting heart rate (RHR) independently predicts cardiovascular mortality. Meanwhile, long-chain n-3 fatty acids (LCn3FAs) have a cardioprotective effect. Our aim was to evaluate whether higher LCn3FAs intake attenuates the elevated risk of cardiovascular mortality associated with increased RHR. Methods: We conducted a population-based 24-year prospective cohort study of Japanese, whose LCn3FAs intake is relatively high. Study participants included 8807 individuals aged 30-95 years from randomly selected areas across Japan without cardiovascular diseases and anti-hypertensive drugs at baseline. The primary endpoint was cardiovascular mortality, and the secondary endpoints were cardiac and stroke mortality during 24 years of follow-up. Individual dietary LCn3FAs intake was estimated from household-based 3-day weighed food records. RHR was obtained from 3 consecutive R-wave intervals on 12-lead electrocardiography. Cox models were used to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for possible confounders. Results: During the follow-up period, 617 cardiovascular deaths were observed. The median daily intake of LCn3FAs was 0.37% kcal (0.86. g/day). The interaction between dietary LCn3FAs intake and RHR in the risk of cardiovascular mortality was statistically significant (p= 0.033). The risk of cardiovascular mortality was significantly higher in the low-intake group (<0.37%. kcal) with an RHR >85. beats/min (bpm) [hazard ratio (HR), 1.67; 95% confidence interval (CI), 1.15-2.43], but not in the high-intake group (≥0.37%. kcal) with an RHR >85. bpm (HR, 0.92; 95% CI, 0.61-1.38), compared with those in the high-intake group with an RHR <70. bpm. Similar results were observed with stroke mortality, but not with cardiac mortality. Conclusions: The risk of cardiovascular mortality associated with increased RHR is elevated in participants with low dietary LCn3FAs intake, but not in participants with high dietary LCn3FAs intake in a representative Japanese general population. These results suggest that high dietary LCn3FAs intake may prevent cardiovascular mortality associated with increased RHR.