title: Dose-dependent decrease of platelet activation and tissue factor by omega-3 polyunsaturated fatty acids in patients with advanced chronic heart failure.
abstract: 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 4 g/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 4 g/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 4 g/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 4 g/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 4 g/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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. deddo.moertl@meduniwien.ac.at
authors.forename: Deddo
authors.initials: D
authors.lastname: Moertl
authors.forename: Rudolf
authors.initials: R
authors.lastname: Berger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hammer
authors.forename: Raisa
authors.initials: R
authors.lastname: Hutuleac
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Kopp
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D023201:CD40 Ligand / Q000097:blood; D002469:Cell Separation; D002908:Chronic Disease; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005434:Flow Cytometry; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D023201:CD40 Ligand; D013925:Thromboplastin