Article Text

Download PDFPDF
Original research article
B-type natriuretic peptide, disease progression and clinical outcomes in atrial fibrillation
  1. Taku Inohara1,
  2. Sunghee Kim1,
  3. Karen Pieper1,
  4. Rosalia G Blanco1,
  5. Larry A Allen2,
  6. Gregg C Fonarow3,
  7. Bernard J Gersh4,
  8. Michael D Ezekowitz5,
  9. Peter R Kowey5,
  10. James A Reiffel6,
  11. Gerald V Naccarelli7,
  12. Paul S Chan8,
  13. Kenneth W Mahaffey9,
  14. Daniel E Singer10,
  15. James V Freeman11,
  16. Benjamin A Steinberg12,
  17. Eric D Peterson1,
  18. Jonathan P Piccini1
  19. on behalf of the ORBIT AF Patients and Investigators
  1. 1 Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA
  2. 2 Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA
  3. 3 Department of Medicine, University of California, Los Angeles, California, USA
  4. 4 Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
  5. 5 Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, USA
  6. 6 College of Physicians and Surgeons, Columbia University, New York City, New York, USA
  7. 7 School of Medicine, Penn State University, Hershey, Pennsylvania, USA
  8. 8 Department of Cardiovascular Research, St Luke’s Mid America Heart Institute, Kansas City, Missouri, USA
  9. 9 Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California, USA
  10. 10 Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA
  11. 11 Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
  12. 12 University of Utah, Salt Lake City, Utah, USA
  1. Correspondence to Dr Taku Inohara, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA; taku.inohara{at}


Objective The association with B-type natriuretic peptide (BNP), disease progression and outcomes in patients with atrial fibrillation (AF) has not been thoroughly investigated.

Methods We evaluated the association between BNP levels and outcomes, including AF progression, composite outcome of major adverse cardiovascular or neurological events (MACNE) and major bleeding, via pooled logistic regression and Cox frailty models in Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry. AF progression was defined as either paroxysmal becoming persistent or permanent, or persistent becoming permanent at any follow-up.

Results Among 13 375 patients with AF, 2797 with BNP values at baseline (median age (IQR), 72.0 (63.0–80.0) years; 43.0% women; median BNP, 238 (102–502) ng/L; 42.3% prior heart failure) were included in the models evaluating the association between BNP levels and MACNE or major bleeding. Of these, 1282 patients with paroxysmal or persistent AF at baseline were analysed in AF progression model. The likelihood of AF progression (adjusted OR, 1.11 for every 100 ng/mL; 95% CI 1.03 to 1.19) and MACNE (adjusted HR, 1.11 for every doubling in BNP values; 95% CI 1.01 to 1.22) increased with BNP concentration, while the elevated BNP values were not associated with increased risks of major bleeding. BNP values improved the risk prediction of AF progression and MACNE when added to conventional risk estimates.

Conclusions BNP levels are associated with increased risk of AF progression and cardiovascular outcomes in patients with AF. Further studies are required to assess whether biomarker-based risk stratification improves patient outcomes.

Clinical trial registration NCT01701817.

  • atrial fibrillation

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors TI and JPP had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: TI, KP and JPP. Acquisition, analysis or interpretation of data: TI, SK, KP, RGB, LAA, GCF, BJG, MDE, PRK, JAR, GVN, PSC, KWM, DES, JVF, BAS, EDP and JPP. Drafting of the manuscript: TI, SK, KP and JPP. Critical revision of the manuscript for important intellectual content: SK, KP, RGB, LAA, GCF, BJG, MDE, PRK, JAR, GVN, PSC, KWM, DES, JVF, BAS, EDP and JPP. Statistical analysis: SK and KP. Obtained funding: JPP. Administrative, technical or material support: RGB and JPP. Study supervision: KP, EDP and JPP.

  • Funding This project was supported in part by cooperative agreement 1U19 HS021092 from the Agency of Healthcare Research and Quality, and JSPS Overseas Research Fellowship. The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is sponsored by Janssen Scientific Affairs. With the exception of Janssen Scientific Affairs, the funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

  • Competing interests TI: research grant from JSPS Overseas Research Fellowship and Boston Scientific. LAA: contract with Janssen and Novartis. GCF: consultant/advisory board support from Janssen Pharmaceutical. BJG: member of a Data Safety Monitoring Board for Mount Sinai St Lukes, Boston Scientific, Teva Pharmaceutical Industries, St Jude Medical, Janssen Research & Development, Baxter Healthcare and Cardiovascular Research Foundation; consultant/advisory board for Janssen Scientific Affairs, Cipla, Armetheon and Medtronic. MDE: consultant/advisory board for Boehringer Ingelheim, Diachi Sanko, Pfizer, Bristol-Myers Squibb and Janssen Scientific Affairs. PRK: consultant for Johnson & Johnson. JAR: research grant from Janssen Pharmaceuticals; research support from Boehringer Ingelheim Pharmaceuticals and GlaxoSmithKline; consultancies with Sanofi, Gilead Sciences, CV Therapeutics, GlaxoSmithKline, Merck & Co, Cardiome Pharma, Boehringer Ingelheim Pharmaceuticals and Medtronic; speakers’ bureau income from Sanofi and Boehringer Ingelheim Pharmaceuticals. GVN: research grant from Janssen; consultant/advisory board for Janssen and Daiichi Sankyo. PSC: employee of Janssen; consultant for Optum Rx and Johnson & Johnson. KWM: financial disclosures can be viewed at DES: consultant/advisory board for Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Johnson & Johnson, Pfizer and Medtronic; research grants from Boehringer Ingelheim and Bristol-Myers Squibb. JVF: consultant/advisory board for Janssen Scientific. BAS: research support from Boston Scientific and Janssen; consult for Janssen; speakers’ bureau income from Biosense Webster. EDP: research grant from Janssen Pharmaceuticals and Eli Lilly; consultant for Janssen Pharmaceuticals and Boehringer Ingelheim. JPP: research grant from Agency for Healthcare Research and Quality, ARCA Biopharma, Boston Scientific, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, ResMed, Spectranetics and St Jude Medical; consultant/advisory board for BMS/Pfizer, GlaxoSmithKline, Janssen Pharmaceuticals, Johnson & Johnson, Medtronic and Spectranetics. SK, KP, and RGB have no relationship(s) to disclose.

  • Patient consent Not required.

  • Ethics approval The study was approved by the institutional review board at Duke University (the coordinating centre) and each participating centre obtained local institutional review board approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles