Abstract 3710: Dose-Dependent Effects of N-3-Polyunsaturated Fatty Acids on Left Ventricular Function, Endothelial Dysfunction, and Interleukin-6 in Patients With Severe Chronic Heart Failure of Non-Ischemic Origin
Objectives The GISSI-HF trial demonstrated that 1g of n-3 polyunsaturated fatty acids (n-3 PUFA) provides a small survival advantage in patients with chronic heart failure (CHF). However, for triglyceride lowering a dose-response relationship exists and higher doses (2– 4 g/d) are necessary for a significant reduction of elevated levels. A similar dose-efficacy relationship was found for the treatment of rheumatoid arthritis. We evaluated the effects of different doses of n-3 PUFA on left ventricular ejection fraction (LVEF), flow-mediated vasodilation (FMD), and interleukin-6 in patients with severe CHF of non-ischemic origin.
Methods and Results A total of 44 patients with severe CHF of non-ischemic origin were randomly assigned to treatment with 1g n-3 PUFA/day (n=14), or 4g n-3 PUFA/day (n=13), or placebo (n=16) for three months. LVEF significantly increased from 24±8% to 27±8% with 1g n-3 PUFA/day (p=0.02), and from 24±7% to 29±8% with 4g n-3 PUFA/day (p=0.005), but remained unchanged by placebo (25±6% and 26±5%; n.s.). FMD increased in trend from 8.3±5.3% to 10.2±4.3% with 1g n-3 PUFA/day (p=0.07), increased significantly from 8.4±4.8% to 11.6±7.0% with 4g n-3 PUFA/day (p=0.01), but remained unchanged by placebo (8,5±7,6% and 8,4±4,4%; n.s.). Interleukin-6 levels decreased in trend from 4.5±6.6% to 1.6±2.1% with 1g n-3 PUFA/day (p=0.1), decreased significantly from 3.0±2.9% to 0.7±0.8% with 4g n-3 PUFA/day (p=0.03), but remained unchanged by placebo (3.6±6.2% and 3.7±6.4%; n.s.). Differences in LVEF were dose-dependent (p=0.03).
Conclusion Treatment with n-3 PUFA for three months improves LVEF and endothelial function and decreases interleukin-6 levels. The improvement of LVEF was dose-dependent.