title: Platelet hyperaggregability in patients with atrial fibrillation. Evidence of a background proinflammatory milieu.
abstract: OBJECTIVE
  Atrial fibrillation (AF) is a condition where platelet hyperaggregability is commonly present. We examined potential physiological bases for platelet hyperaggregability in a cohort of patients with acute and chronic AF. In particular, we sought to identify the impact of inflammation [myeloperoxidase (MPO) and C-reactive protein (CRP)] and impaired nitric oxide (NO) signaling.
  
  
  METHODS
  Clinical and biochemical determinants of adenosine diphosphate (ADP)-induced platelet aggregation were sought in patients (n = 106) hospitalized with AF via univariate and multivariate analysis.
  
  
  RESULTS
  Hyper-responsiveness of platelets to ADP was directly (r = 0.254, p < 0.01) correlated with plasma concentrations of thrombospondin-1 (TSP-1), a matricellular protein that impairs NO responses and contributes to development of oxidative stress. In turn, plasma TSP-1 concentrations were directly correlated with MPO concentrations (r = 0.221, p < 0.05), while MPO concentrations correlated with those of asymmetric dimethylarginine (ADMA, r = 0.220, p < 0.05), and its structural isomer symmetric dimethylarginine (SDMA, r = 0.192, p = 0.05). Multivariate analysis identified TSP-1 (β = 0.276, p < 0.05) concentrations, as well as female sex (β = 0.199, p < 0.05), as direct correlates of platelet aggregability, and SDMA concentrations (β = - 0.292, p < 0.05) as an inverse correlate.
  
  
  CONCLUSIONS
  We conclude that platelet hyperaggregability, where present in the context of AF, may be engendered by impaired availability of NO, as well as via MPO-related inflammatory activation.
authors.affiliation: Basil Hetzel Institute, Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Cardiology Unit, 28 Woodville Rd, Woodville South, 5011, SA, Australia.
authors.forename: Nathan E K
authors.initials: NE
authors.lastname: Procter
authors.affiliation: National Health and Medical Research Council (NHMRC) Centre of Research Excellence to Reduce Inequality in Heart Disease, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
authors.forename: Jocasta
authors.initials: J
authors.lastname: Ball
authors.affiliation: Basil Hetzel Institute, Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Cardiology Unit, 28 Woodville Rd, Woodville South, 5011, SA, Australia.
authors.forename: Doan T M
authors.initials: DT
authors.lastname: Ngo
authors.affiliation: Basil Hetzel Institute, Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Cardiology Unit, 28 Woodville Rd, Woodville South, 5011, SA, Australia.
authors.forename: Yuliy Y
authors.initials: YY
authors.lastname: Chirkov
authors.affiliation: Heart, Lung, Blood and Vascular Medicine Institute, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Isenberg
authors.affiliation: School of Medicine, Boston University, Boston, MA, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: National Health and Medical Research Council (NHMRC) Centre of Research Excellence to Reduce Inequality in Heart Disease, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.|Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Stewart
authors.affiliation: Basil Hetzel Institute, Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Cardiology Unit, 28 Woodville Rd, Woodville South, 5011, SA, Australia. john.horowitz@adelaide.edu.au.
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood / Q000276:immunology*; D009195:Peroxidase / Q000097:blood / Q000276:immunology; D010974:Platelet Aggregation / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000097:blood / Q000276:immunology*
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D009195:Peroxidase
keywords: Asymmetric dimethylarginine; Atrial fibrillation; Myeloperoxidase; Platelet aggregation; Thrombospondin-1