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Dose-dependent decrease of platelet activation and tissue factor by omega-3 polyunsaturated fatty acids in patients with advanced chronic heart failure

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH11-03-0169
Issue: 2011: 106/3 (Sep) pp. 389–565
Pages: 457-465

Dose-dependent decrease of platelet activation and tissue factor by omega-3 polyunsaturated fatty acids in patients with advanced chronic heart failure

Online Supplementary Material

D. Moertl (1, 2), R. Berger (1), A. Hammer (3), R. Hutuleac (1), R. Koppensteiner (3), C. W. Kopp (3), S. Steiner (3)

(1) Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; (2) Department of Internal Medicine III (Cardiology), Landesklinikum St. Poelten, St. Poelten, Austria; (3) Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

Summary

Chronic heart failure (CHF) is characterised by activation of neuroendocrine and inflammatory pathways, and both are linked to a prothrombotic state. Treatment with omega-3 polyunsaturated fatty acids (n3-PUFA) showed significant benefits including mortality reduction in CHF, but exact mechanisms of action are still unclear. We investigated the effects of n3-PUFA on markers of platelet activation and thrombogenesis in patients with severe CHF. Thirty-six patients with non-ischaemic CHF (LVEF<35%, NYHA class>2) under optimised therapy were randomised to supplementation with 1g/day or 4g/day n3-PUFA, or placebo for 12 weeks. Using whole-blood flow cytometry, monocyte-platelet aggregates characterised by CD14+/CD42b+ co-expression and monocytic tissue factor (TF) were determined. Plasma levels of P-selectin, sCD40L, fibrinogen, prothrombin fragment F1.2, TF and pro-inflammatory markers (high sensitive[hs] interleukin-6, hsCRP, hsTNF-alpha, monocyte chemotactic protein-1) were measured by immunoassay. Supplementation with 1g/day and 4g/day n3-PUFA but not placebo significantly reduced monocyte-platelet aggregates in a dose-dependent manner (p for trend=0.02 across the groups). A dose of 4g/day but not 1g/day n3-PUFA significantly decreased P-selectin (p=0.03). Plasma TF decreased dose-dependently upon n3-PUFA supplementation (p for trend=0.02), paralleled by a significant decrease of TF+-monocytes (p for trend=0.01). The amount of 4g/day n3-PUFA exhibited modest anti-inflammatory effects with a significant reduction of hs interleukin-6 (p<0.01) and a trend-wise reduction of hsTNF-alpha (p=0.09). No changes were seen for sCD40L, fibrinogen, hsCRP and monocyte chemotactic protein-1, while F1.2 was decreased by 4g/day n3-PUFA (P=0.03). In patients with severe non-ischaemic CHF, treatment with n3-PUFA leads to a dose-dependent decrease of platelet activation and TF. Higher dosage exhibits also anti-inflammatory effects.

Keywords

fatty acids, inflammation, Heart failure, Platelets, Tissue factor

DOI

http://dx.doi.org/10.1160/TH11-03-0169

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