title: NT-proBNP is a powerful predictor for incident atrial fibrillation - Validation of a multimarker approach.
abstract: BACKGROUND
  Biomarkers may be of value to identify individuals at risk of developing atrial fibrillation (AF). Using a multimarker approach, this study investigated if the biomarkers; NT-proBNP, high-sensitivity cardiac troponin (hs-cTn), growth differentiation factor-15 (GDF-15), cystatin C and high-sensitivity C-reactive protein (CRP) are independent predictors for incident AF.
  
  
  METHODS
  Blood samples were collected from 883 individuals in the Uppsala Longitudinal Study of Adult Men (ULSAM) and 978 individuals in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Participants were followed for 10-13years with n=113 incident AF cases in ULSAM and n=148 in PIVUS. The associations between biomarkers and incident AF were analysed in Cox proportional hazards regression models.
  
  
  RESULTS
  The hazard ratio (HR) for incident AF was significant for all five biomarkers in unadjusted analyses in both cohorts. Only NT-proBNP remained significant when adjusting for cardiovascular risk factors and the other biomarkers (HR (1SD) 2.05 (1.62-2.59) (ULSAM) and 1.56 (1.30-1.86) (PIVUS), both p<0.001). The C-index improved from 0.64 to 0.69 in ULSAM and from 0.62 to 0.68 in PIVUS, by adding NT-proBNP to cardiovascular risk factors (both p<0.001). The C-index of the CHARGE-AF risk score increased from 0.62 to 0.68 (ULSAM) and 0.60 to 0.66 (PIVUS) by addition of NT-proBNP (p<0.001).
  
  
  CONCLUSIONS
  Using a multimarker approach NT-proBNP was the strongest predictor of incident AF in two cohorts, and improved risk prediction when added to traditional risk factors. NT-proBNP significantly improved the predictive ability of the novel CHARGE-AF risk score, although the predictive value remained modest.
authors.affiliation: Karolinska Institutet, Dept. of Clinical Sciences, Cardiology Unit, Danderyd's University Hospital, Stockholm, Sweden. Electronic address: emma.svennberg@ds.se.
authors.forename: Emma
authors.initials: E
authors.lastname: Svennberg
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Lindahl
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Berglund
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Kai M
authors.initials: KM
authors.lastname: Eggers
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.affiliation: Department of Public Health/Geriatrics, Uppsala University and Medical Products Agency/Scientific Support, Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Zethelius
authors.affiliation: Karolinska Institutet, Dept. of Clinical Sciences, Cardiology Unit, Danderyd's University Hospital, Stockholm, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Rosenqvist
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Hijazi
mesh_terms: D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D055316:Cystatin C / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein
keywords: Atrial fibrillation; Biomarkers; C-reactive protein; Cystatin C; Growth differentiating factor 15; Natriuretic peptide; Troponin