title: Relations of biomarkers of distinct pathophysiological pathways and atrial fibrillation incidence in the community.
abstract: BACKGROUND
  Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial.
  
  
  RESULTS
  In 3120 Framingham cohort participants (mean age 58.4+/-9.7 years, 54% women), we related 10 biomarkers that represented inflammation (C-reactive protein and fibrinogen), neurohormonal activation (B-type natriuretic peptide [BNP] and N-terminal proatrial natriuretic peptide), oxidative stress (homocysteine), the renin-angiotensin-aldosterone system (renin and aldosterone), thrombosis and endothelial function (D-dimer and plasminogen activator inhibitor type 1), and microvascular damage (urinary albumin excretion; n=2673) to incident AF (n=209, 40% women) over a median follow-up of 9.7 years (range 0.05 to 12.8 years). In multivariable-adjusted analyses, the biomarker panel was associated with incident AF (P<0.0001). In stepwise-selection models (P<0.01 for entry and retention), log-transformed BNP (hazard ratio per SD 1.62, 95% confidence interval 1.41 to 1.85, P<0.0001) and C-reactive protein (hazard ratio 1.25, 95% confidence interval 1.07 to 1.45, P=0.004) were chosen. The addition of BNP to variables recently combined in a risk score for AF increased the C-statistic from 0.78 (95% confidence interval 0.75 to 0.81) to 0.80 (95% confidence interval 0.78 to 0.83) and showed an integrated discrimination improvement of 0.03 (95% confidence interval 0.02 to 0.04, P<0.0001), with 34.9% relative improvement in reclassification analysis. The combined analysis of BNP and C-reactive protein did not appreciably improve risk prediction over the model that incorporated BNP in addition to the risk factors.
  
  
  CONCLUSIONS
  BNP is a predictor of incident AF and improves risk stratification based on well-established clinical risk factors. Whether knowledge of BNP concentrations may be used to target individuals at risk of AF for more intensive monitoring or primary prevention requires further investigation.
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Study, Framingham, Mass, USA.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Yamamoto
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sullivan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Tofler
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011237:Predictive Value of Tests; D012111:Residence Characteristics; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain