B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: The CHARGE-AF Consortium of community-based cohort studies

Moritz F. Sinner, Katherine A. Stepas, Carlee B. Moser, Bouwe P. Krijthe, Thor Aspelund, Nona Sotoodehnia, João D. Fontes, A. Cecile J.W. Janssens, Richard A. Kronmal, Jared W. Magnani, Jacqueline C. Witteman, Alanna M. Chamberlain, Steven A. Lubitz, Renate B. Schnabel, Ramachandran S. Vasan, Thomas J. Wang, Sunil K. Agarwal, David D. McManus, Oscar H. Franco, Xiaoyan YinMartin G. Larson, Gregory L. Burke, Lenore J. Launer, Albert Hofman, Daniel Levy, John S. Gottdiener, Stefan Kääb, David Couper, Tamara B. Harris, Brad C. Astor, Christie M. Ballantyne, Ron C. Hoogeveen, Andrew E. Arai, Elsayed Z. Soliman, Patrick T. Ellinor, Bruno H.C. Stricker, Vilmundur Gudnason, Susan R. Heckbert, Michael J. Pencina, Emelia J. Benjamin, Alvaro Alonso

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Aims: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain.We sought to improve risk stratification for AF using biomarker information. Methods and results: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon).We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [Cstatistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56- 1.76], P < 0.0001 and 1.18 (95% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022-0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion: B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. Published by Oxford University Press on behalf of the European Society of Cardiology 2014.

Original languageEnglish (US)
Pages (from-to)1426-1433
Number of pages8
Issue number10
StatePublished - Oct 2014


  • Atrial fibrillation
  • B-type natriuretic peptide
  • Biomarker
  • C-reactive protein
  • Epidemiology
  • Risk prediction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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