TY - JOUR
AU - Tavazzi L.
AU - Marchioli R.
AU - Wu J.
AU - Mozaffarian D.
AU - Brown N.
AU - Masson S.
AU - Simon C.
AU - Lombardi F.
AU - Silletta M.
AU - Sellke F.
AU - Libby P.
AU - Milne G.
AU - Damiano R. Jr.
AU - Marsala J.
AU - Rinaldi M.
AU - Domenech A.
AB - <p>
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. METHODS AND 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 &gt;/=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&lt;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. CLINICAL TRIAL REGISTRATION: URL: Clinicaltrials.gov Unique identifier: NCT00970489.
</p>

AD - George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.Y.W.).<br/>Hematology-Oncology Therapeutic Delivery Unit, Quintiles, Milan, Italy (R.M.).<br/>Laboratory of Clinical Epidemiology of Cardiovascular Disease, Fondazione Mario Negri Sud, Santa Maria Imbaro, Italy (M.G.S.).<br/>Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy (S.M.).<br/>Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI (F.W.S.).<br/>Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.L.).<br/>Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (G.L.M.).<br/>Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (N.J.B.).<br/>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.).<br/>Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, MO (R.J.D., J.M.).<br/>Division of Cardiac Surgery, Citta'della Salute e della Scienza, University of Turin, Italy (M.R.).<br/>Department of Cardiovascular Surgery, Italian Hospital of Buenos Aires, Argentina (A.D.).<br/>Cardiovascular Department, Cardiac Surgery, Ospedali Riuniti di Bergamo, Italy (C.S.).<br/>Maria Cecilia Hospital, GVM Care & Research-E.S. Health Science Foundation, Cotignola, Italy (L.T.).<br/>Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
AN - 25994442
BT - Journal of the American Heart Association
DA - -45414416051
DP - NLM
ET - 2015/05/23
LA - eng
LB - AUS<br/>FP<br/>FY16
M1 - 5
N1 - Wu, Jason H Y<br/>Marchioli, Roberto<br/>Silletta, Maria G<br/>Masson, Serge<br/>Sellke, Frank W<br/>Libby, Peter<br/>Milne, Ginger L<br/>Brown, Nancy J<br/>Lombardi, Federico<br/>Damiano, Ralph J Jr<br/>Marsala, Joann<br/>Rinaldi, Mauro<br/>Domenech, Alberto<br/>Simon, Caterina<br/>Tavazzi, Luigi<br/>Mozaffarian, Dariush<br/>1 RC2 HL101816/HL/NHLBI NIH HHS/United States<br/>R01HL085710/HL/NHLBI NIH HHS/United States<br/>RC2 HL101816/HL/NHLBI NIH HHS/United States<br/>Research Support, N.I.H., Extramural<br/>Research Support, Non-U.S. Gov't<br/>England<br/>J Am Heart Assoc. 2015 May 20;4(5). pii: e001886. doi: 10.1161/JAHA.115.001886.
N2 - <p>
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. METHODS AND 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 &gt;/=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&lt;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. CLINICAL TRIAL REGISTRATION: URL: Clinicaltrials.gov Unique identifier: NCT00970489.
</p>

PY - 2015
SN - 2047-9980 (Electronic)<br/>2047-9980 (Linking)
T2 - Journal of the American Heart Association
TI - Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Trial
VL - 4
Y2 - FY16
ER -