Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: A double-blind, placebo-controlled, 3-arm study

Background Supplementation with 1 g/d omega-3-polyunsaturated fatty acids (n3-PUFAs) demonstrated a small survival advantage in patients with chronic heart failure (CHF) in the GISSI-HF trial. However, a dose-efficacy relationship was postulated for the beneficial effects of n3-PUFA before. Therefore, we evaluated dose-dependent effects of n3-PUFA in patients with severe CHF. Methods In a double-blind, randomized, controlled pilot trial, 43 patients with severe, nonischemic heart failure received 1 g/d n3-PUFA (n = 14), 4 g/d n3-PUFA (n = 13), or placebo (n = 16) for 3 months. Changes in left ventricular ejection fraction (LVEF), flow-mediated vasodilation, plasma high-sensitive interleukin 6 and high-sensitive tumor necrosis factor a, and exercise peak oxygen consumption were assessed. Results Left ventricular ejection fraction increased in a dose-dependent manner (P = .01 for linear trend) in the 4 (baseline vs 3 months [mean +/- SD]: 24% +/- 7% vs 29% +/- 8%, P = .005) and 1 g/d treatment groups (24% +/- 8% vs 27% +/- 8%, P = .02). Flow-mediated vasodilation increased significantly with high-dose 4 g/d n3-PUFA (8.4% +/- 4.8% vs 11.6% +/- 7.0%, P = .01) but only trendwise with low-dose 1 g/d (8.3% +/- 5.3% vs 10.2% +/- 4.3%, P = .07). Interleukin 6 significantly decreased with 4 g/d n3-PUFA (3.0 +/- 2.9 pg/mL vs 0.7 +/- 0.8 pg/mL, P = .03) but only trendwise with 1 g/d (4.5 +/- 6.6 pg/mL to 1.6 +/- 2.1 pg/mL, P = .1). High-sensitive tumor necrosis factor a decreased trendwise with 4 g/d n3-PUFA but remained unchanged with 1 g/d. In patients with maximal exercise effort, only 4 g/d increased the peak oxygen consumption. No changes in any investigated parameters were noted with placebo. Conclusion Treatment with n3-PUFA for 3 months exerts a dose-dependent increase of LVEF in patients with CHF. In parallel, a significant improvement of endothelial function and decrease of interleukin 6 is found with high-dose n3-PUFA intervention. (Am Heart J 2011;161:915.e1-915.e9.)