Moritz F Sinner1, Katherine A Stepas2, Carlee B Moser2, Bouwe P Krijthe3, Thor Aspelund4, Nona Sotoodehnia5, João D Fontes6, A Cecile J W Janssens3, Richard A Kronmal7, Jared W Magnani8, Jacqueline C Witteman3, Alanna M Chamberlain9, Steven A Lubitz10, Renate B Schnabel11, Ramachandran S Vasan12, Thomas J Wang13, Sunil K Agarwal14, David D McManus15, Oscar H Franco16, Xiaoyan Yin17, Martin G Larson6, Gregory L Burke18, Lenore J Launer19, Albert Hofman3, Daniel Levy20, John S Gottdiener21, Stefan Kääb22, David Couper23, Tamara B Harris19, Brad C Astor24, Christie M Ballantyne25, Ron C Hoogeveen26, Andrew E Arai27, Elsayed Z Soliman28, Patrick T Ellinor10, Bruno H C Stricker29, Vilmundur Gudnason4, Susan R Heckbert30, Michael J Pencina2, Emelia J Benjamin31, Alvaro Alonso32. 1. Department of Medicine I, University Hospital Munich, Ludwig-Maximilians University, 81377 Munich, Germany. 2. Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA. 3. Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands Netherlands Consortium for Healthy Aging (NCHA), 2300 RC Leiden, The Netherlands. 4. Icelandic Heart Association, Research Institute, IS-201 Kopavogur, Iceland The University of Iceland, IS-101 Reykjavik, Iceland. 5. Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA. 6. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA. 7. Department of Biostatistics, University of Washington, Seattle, WA 98195, USA. 8. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. 9. Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. 10. Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MA 02114, USA. 11. Department of General and Interventional Cardiology, University Heart Center, 20246 Hamburg-Eppendorf, Germany. 12. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA. 13. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA Cardiology Division, Massachusetts General Hospital, Boston, MA 02114, USA. 14. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA. 15. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA Departments of Medicine and Quantitative Health Sciences, University of Massachusetts, Worcester, MA 01605, USA Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USA. 16. Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands. 17. Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA. 18. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 19. Laboratory of Epidemiology, Demography, and Biometry, National Institute of Aging, National Institutes of Health, Bethesda, MD 20892, USA. 20. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA Center for Population Studies, NHLBI, Framingham, MA 01702, USA. 21. Division of Cardiology, University of Maryland Medical Center, Baltimore, MD 21201, USA. 22. Department of Medicine I, University Hospital Munich, Ludwig-Maximilians University, 81377 Munich, Germany Deutsches Zentrum für Herz-Kreislauferkrankungen (DZHK), partner site Munich Heart Alliance, 80802 Munich, Germany. 23. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA. 24. University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705, USA. 25. Baylor College of Medicine, Houston, TX 77030, USA Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, USA. 26. Baylor College of Medicine, Houston, TX 77030, USA. 27. Cardiovascular and Pulmonary Branch, NHLBI, Bethesda, MD 20892, USA. 28. Epidemiological Cardiology Research Center (EPICARE), Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. 29. Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands Netherlands Consortium for Healthy Aging (NCHA), 2300 RC Leiden, The Netherlands Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands Inspectorate for Health Care, 3500 GR The Hague, The Netherlands Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands. 30. Department of Epidemiology, University of Washington, Seattle, WA 98195, USA. 31. National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA alonso@umn.edu emelia@bu.edu. 32. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA alonso@umn.edu emelia@bu.edu.
Abstract
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 [C-statistic, 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, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 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. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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 [C-statistic, 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, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 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. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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