title: Impaired platelet nitric oxide response in patients with new onset atrial fibrillation.
abstract: BACKGROUND
  Clinical factors associated with thromboembolic risk in AF patients are well characterized and include new onset AF. Biochemically, AF is associated with inflammatory activation and impairment of nitric oxide (NO) signalling, which may also predispose to thromboembolism: the bases for variability in these anomalies have not been identified. We therefore sought to identify correlates of impaired platelet NO signalling in patients hospitalized with atrial fibrillation (AF), and to evaluate the impact of acuity of AF.
  
  
  METHODS
  87 patients hospitalized with AF were evaluated. Platelet aggregation, and its inhibition by the NO donor sodium nitroprusside, was evaluated using whole blood impedance aggregometry. Correlates of impaired NO response were examined and repeated in a "validation" cohort of acute cardiac illnesses.
  
  
  RESULTS
  Whilst clinical risk scores were not significantly correlated with integrity of NO signalling, new onset AF was associated with impaired NO response (6 ± 5% inhibition versus 25 ± 4% inhibition for chronic AF, p<0.01). New onset AF was a multivariate correlate (p<0.01) of impaired NO signalling, along with platelet ADP response (p<0.001), whereas the associated tachycardia was not. Platelet ADP response was predicted by elevation of plasma thrombospondin-1 concentrations (p<0.01). Validation cohort evaluations confirmed that acute AF was associated with significant (p<0.05) impairment of platelet NO response, and that neither acute heart failure nor acute coronary syndromes were associated with similar impairment.
  
  
  CONCLUSIONS
  Recent onset of AF is associated with marked impairment of platelet NO response. These findings may contribute to thromboembolic risk in such patients.
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Nathan E K
authors.initials: NE
authors.lastname: Procter
authors.affiliation: National Health and Medical Research Council (NHMRC), Centre of Excellence to Reduce Inequality in Heart Disease, Baker IDI Heart and Diabetes Institute, Australian Catholic University, Melbourne, Australia.
authors.forename: Jocasta
authors.initials: J
authors.lastname: Ball
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Saifei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Nicola
authors.initials: N
authors.lastname: Hurst
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of South Australia, Adelaide, Australia.
authors.forename: Vivek B
authors.initials: VB
authors.lastname: Nooney
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goh
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Stafford
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Tamila
authors.initials: T
authors.lastname: Heresztyn
authors.affiliation: National Health and Medical Research Council (NHMRC), Centre of Excellence to Reduce Inequality in Heart Disease, Baker IDI Heart and Diabetes Institute, Australian Catholic University, Melbourne, Australia.
authors.forename: Melinda
authors.initials: M
authors.lastname: Carrington
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Doan T M
authors.initials: DT
authors.lastname: Ngo
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Vascular Medicine Institute, University of Pittsburgh Department of Medicine, Pittsburgh, PA, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Isenberg
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
authors.forename: Yuliy Y
authors.initials: YY
authors.lastname: Chirkov
authors.affiliation: National Health and Medical Research Council (NHMRC), Centre of Excellence to Reduce Inequality in Heart Disease, Baker IDI Heart and Diabetes Institute, Australian Catholic University, Melbourne, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Stewart
authors.affiliation: Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia. Electronic address: 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 / Q000097:blood* / Q000175:diagnosis*; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D010979:Platelet Function Tests / Q000379:methods; D012307:Risk Factors
chemical_list: D009569:Nitric Oxide
keywords: Atrial fibrillation; Nitric oxide; Platelets