title: Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Trial.
abstract: BACKGROUND
  Animal study results point to oxidative stress as a key mechanism triggering postoperative atrial fibrillation (PoAF), yet the extent to which specific biomarkers of oxidative stress might relate to PoAF risk in humans remains speculative.
  
  
  RESULTS
  We assessed the association of validated, fatty acid-derived oxidative stress biomarkers (F2-isoprostanes, isofurans, and F3-isoprostanes) in plasma and urine, with incident PoAF among 551 cardiac surgery patients. Biomarkers were measured at enrollment, the end of surgery, and postoperative day 2. PoAF lasting ≥30 seconds was confirmed with rhythm strip or electrocardiography and centrally adjudicated. Outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Urine level of each oxidative stress biomarker rose at the end of surgery (2- to 3-fold over baseline, P<0.001) and subsequently declined to concentrations comparable to baseline by postoperative day 2. In contrast, plasma concentrations remained relatively stable throughout the perioperative course. Urine F2-isoprostanes and isofurans at the end of surgery were 20% and 50% higher in subjects who developed PoAF (P≤0.009). While baseline biomarker levels did not associate significantly with PoAF, end of surgery and postoperative day 2 isoprostanes and isofurans demonstrated relatively linear associations with PoAF. For example, the end of surgery extreme quartile multivariate adjusted OR (95% CI) for urine isofurans and F3-isoprostanes were 1.95 (1.05 to 3.62; P for trend=0.01) and 2.10 (1.04 to 2.25, P for trend=0.04), respectively. The associations of biomarkers with PoAF varied little by demographics, surgery type, and medication use (P≥0.29 for each).
  
  
  CONCLUSIONS
  These novel results add to accumulating evidence supporting the likely key pathogenic role of elevated oxidative stress in PoAF.
  
  
  BACKGROUND
  URL: Clinicaltrials.gov Unique identifier: NCT00970489.
authors.affiliation: George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.Y.W.).
authors.forename: Jason H Y
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Hematology-Oncology Therapeutic Delivery Unit, Quintiles, Milan, Italy (R.M.).
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchioli
authors.affiliation: Laboratory of Clinical Epidemiology of Cardiovascular Disease, Fondazione Mario Negri Sud, Santa Maria Imbaro, Italy (M.G.S.).
authors.forename: Maria G
authors.initials: MG
authors.lastname: Silletta
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy (S.M.).
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI (F.W.S.).
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (G.L.M.).
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (N.J.B.).
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.affiliation: U.O.C. di Malattie Cardiovascolari, Fondazione IRCCS Ospedale Maggiore Policlinico, Dipartimento di Scienze Cliniche e di Communita, Universita degli Studi di Milano, Italy (F.L.).
authors.forename: Federico
authors.initials: F
authors.lastname: Lombardi
authors.affiliation: Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, MO (R.J.D., J.M.).
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Damiano
authors.affiliation: Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, MO (R.J.D., J.M.).
authors.forename: Joann
authors.initials: J
authors.lastname: Marsala
authors.affiliation: Division of Cardiac Surgery, Citta'della Salute e della Scienza, University of Turin, Italy (M.R.).
authors.forename: Mauro
authors.initials: M
authors.lastname: Rinaldi
authors.affiliation: Department of Cardiovascular Surgery, Italian Hospital of Buenos Aires, Argentina (A.D.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Domenech
authors.affiliation: Cardiovascular Department, Cardiac Surgery, Ospedali Riuniti di Bergamo, Italy (C.S.).
authors.forename: Caterina
authors.initials: C
authors.lastname: Simon
authors.affiliation: Maria Cecilia Hospital, GVM Care & Research-E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.affiliation: Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
mesh_terms: D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood*; D004042:Dietary Fats, Unsaturated / Q000627:therapeutic use; D004562:Electrocardiography; D028441:F2-Isoprostanes / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D028421:Isoprostanes / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011183:Postoperative Complications / Q000178:diet therapy / Q000517:prevention & control*; D011184:Postoperative Period; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004042:Dietary Fats, Unsaturated; D028441:F2-Isoprostanes; D015525:Fatty Acids, Omega-3; D028421:Isoprostanes
keywords: atrial fibrillation; cardiac surgery; isofurans; isoprostanes; oxidative stress