title: Genetic and clinical risk prediction model for postoperative atrial fibrillation.
abstract: BACKGROUND
  Postoperative atrial fibrillation (PoAF) is common after coronary artery bypass grafting. We previously showed that atrial fibrillation susceptibility single nucleotide polymorphisms (SNPs) at the chromosome 4q25 locus are associated with PoAF. Here, we tested the hypothesis that a combined clinical and genetic model incorporating atrial fibrillation risk SNPs would be superior to a clinical-only model.
  
  
  RESULTS
  We developed and externally validated clinical and clinical/genetic risk models for PoAF. The discovery and validation cohorts included 556 and 1164 patients, respectively. Clinical variables previously associated with PoAF and 13 SNPs at loci associated with atrial fibrillation in genome-wide association studies were considered. PoAF occurred in 30% and 29% of patients in the discovery and validation cohorts, respectively. In the discovery cohort, a logistic regression model with clinical factors had good discrimination, with an area under the receiver operator characteristic curve of 0.76. The addition of 10 SNPs to the clinical model did not improve discrimination (area under receiver operator characteristic curve, 0.78; P=0.14 for difference between the 2 models). In the validation cohort, the clinical model had good discrimination (area under the receiver operator characteristic curve, 0.69) and addition of genetic variables resulted in a marginal improvement in discrimination (area under receiver operator characteristic curve, 0.72; P<0.0001).
  
  
  CONCLUSIONS
  We developed and validated a model for the prediction of PoAF containing common clinical variables. Addition of atrial fibrillation susceptibility SNPs did not improve model performance. Tools to accurately predict PoAF are needed to risk stratify patients undergoing coronary artery bypass grafting and identify candidates for prophylactic therapies.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kolek
authors.affiliation: Department of Anesthesiology, Perioperative & Pain Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA.
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Muehlschlegel
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN.
authors.forename: William S
authors.initials: WS
authors.lastname: Bush
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Babar
authors.initials: B
authors.lastname: Parvez
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.|Department of Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Murray
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.|Department of Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: M Benjamin
authors.initials: MB
authors.lastname: Shoemaker
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blair
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: Kaylen C
authors.initials: KC
authors.lastname: Kor
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.|Department of Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Department of Anesthesiology, Vanderbilt University, Nashville, TN.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Donahue
authors.affiliation: Department of Anesthesiology & Pain Management, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Fox
authors.affiliation: Department of Anesthesiology, Perioperative & Pain Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA.
authors.forename: Stanton K
authors.initials: SK
authors.lastname: Shernan
authors.affiliation: Department of Anesthesiology, Texas Heart Institute, St. Luke's Hospital, Houston, TX.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Collard
authors.affiliation: Department of Anesthesiology, Perioperative & Pain Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Body
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D016002:Discriminant Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012372:ROC Curve; D012042:Registries; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States
keywords: atrial fibrillation; cardiac surgery; genetics; postoperative complication arrhythmia; risk model