N-3 fatty acids and the risk of sudden cardiac death assessed by 24-hour heart rate variability.

Abstract

Dietary n-3 polyunsaturated fatty acids (PUFA) may reduce the incidence of sudden cardiac death (SCD) in humans possibly due to an antiarrhythmic effect. However, only sparse information exists on such an effect in humans. Therefore, we performed three double-blinded intervention trials with n23 PUFA in three different groups: in patients with a previous myocardial infarction (MI) (1,2), in patients with chronic renal failure and at high risk of SCD (3), and in healthy volunteers (Christensen, J.H., Christensen, M.S., Dyerberg, J., and Schmidt, E.B., unpublished data). The end point in the trials was 24-h heart rate variability (HRV), and the clinically important HRV parameter SDNN [standard deviation of all normal RR intervals during a 24-h electrocardiogram (ECG) recording] was used. HRV is a powerful predictor of mortality and of arrhythmic events in humans. The relationship between fish consumption, the content of n-3 PUFA in platelets, and 24-h HRV was examined in 55 post-MI patients (mean age 63 _+ 7 yr) with left ventricular dysfunction (mean ejection fraction 0.33 _+ 0.05). The patients were divided into three groups: (i) Those who never ate fish, (ii) those who ate fish once a week, and (iii) those eating fish at least twice a week. A close positive correlation was observed between fish intake and the cellular content of n-3 PUFA. HRV tended to be higher among those who consumed one fish meal per week compared to no fish (122 vs. 103 ms, P = 0.07). Furthermore, a significant positive correlation was found between the cellular content of n-3 PUFA and HRV (r = 0.30, P < 0.05). These post-MI patients were now randomly allocated to receive either 5.2 g of n-3 PUFA daily or placebo oil for 12 wk. After dietary supplementation, HRV increased from 115 to 124 ms (significant compared to baseline and to placebo, P = 0.01). The relationship between the cellular content of n-3 PUFA and HRV was also examined in patients with chronic renal failure. Twenty-nine patients (mean age 52 _+ 15 yr) received 5.2 g of PUFA or olive oil daily for 12 wk. After dietary supplementation, a close positive correlation was found between the cellular content of n-3 PUFA and HRV (r = 0.71, P < 0.01). Finally, 60 healthy subjects (25 women, mean age 38 yr; 35 men, mean age 38 yr) were randomized to either (i) 2.0 g of n-3 PUFA daily, or (ii) 6.6 g of n-3 PUFA daily, or (iii) placebo for 12 wk. At baseline, a close positive correlation was found between n-3 PUFA in granulocytes and HRV. Furthermore, the subjects with a low HRV at baseline had a dosedependent increase in HRV after n-3 PUFA supplementation. In conclusion, the results showed a beneficial effect of n-3 PUFA on HRV in three different populations, strongly indicating an antiarrhythmic effect of n-3 PUFA. Our data may explain the findings from other studies, namely that a low occurrence of SCD is observed in subjects with and without coronary heart disease who regularly eat fish.