Author + information
- Received January 10, 2010
- Revision received April 12, 2010
- Accepted May 3, 2010
- Published online November 16, 2010.
- J. Gustav Smith, MD*,†,‡,* (, )
- Christopher Newton-Cheh, MD, MPH‡,§∥,
- Peter Almgren, MSc*,
- Joachim Struck, PhD¶,
- Nils G. Morgenthaler, MD, PhD¶,
- Andreas Bergmann, PhD¶,
- Pyotr G. Platonov, MD, PhD†,
- Bo Hedblad, MD, PhD*,
- Gunnar Engström, MD, PhD*,
- Thomas J. Wang, MD∥ and
- Olle Melander, MD, PhD*
- ↵*Reprint requests and correspondence:
Dr. J. Gustav Smith, Department of Clinical Sciences, Lund University, 221 85 Lund, Sweden
Objectives The purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways.
Background Heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals are limited.
Methods In 5,187 individuals from the community-based MDCS (Malmö Diet and Cancer Study), we studied the performance of conventional risk factors and 6 biomarkers including midregional pro-atrial natriuretic peptide (MR-proANP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein (CRP), and copeptin.
Results During a mean follow-up of 14 years, 112 individuals were diagnosed with heart failure and 284 individuals with atrial fibrillation. NT-proBNP (hazard ratio [HR]: 1.63 per SD, 95% confidence interval [CI]: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p < 0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted incident heart failure independently of conventional risk factors and other biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR: 1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial fibrillation. Addition of biomarkers to conventional risk factors improved c-statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for atrial fibrillation and the integrated discrimination improvement for both diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification.
Conclusions Conventional cardiovascular risk factors predict incident heart failure and atrial fibrillation with reasonable accuracy in middle-age individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve risk classification for heart failure.
Continuing Medical Education (CME) is available for this article.
The Malmö Diet and Cancer study was made possible by grants from the Malmö city council. Biomarker measurements were performed and funded by BRAHMS AGand Siemens Diagnostics. Drs. Smith, Platonov, Hedblad, Engström, and Melander were supported by the Swedish Heart-Lung Foundation. Dr. Newton-Cheh was supported by National Institutes of Health(NIH) grant K23-HL-080025, a Doris Duke Charitable Foundation Clinical Scientist Development Award, a Burroughs Wellcome Fund Career Award for Medical Scientists, and served on the advisory board for Merck. Dr. Platonov was supported by the governmental funding of clinical research within the Swedish NHS. Dr. Wang was supported by NIHgrants R01-HL-086875, R01-HL-083197, and R01-DK-081572and by a grant from the American Heart Association. Drs. Hedblad and Melander were supported by the Swedish Medical Research Council. Dr. Engström is employed by AstraZeneca R&D. Dr. Melander was supported by grants from the Medical Faculty of Lund University, Malmö University Hospital, the Albert Påhlsson Research Foundation, the Crafoord Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Fund, the Lennart Hanssons Memorial Fund, and the Wallenberg Foundation. Drs. Struck, Morgenthaler, and Bergmann are employees of Brahms AG, which holds patent rights on the assays used for MR-proADM, MR-proANP, and Copeptin. Drs. Wang and Melander contributed equally to this work.
- Received January 10, 2010.
- Revision received April 12, 2010.
- Accepted May 3, 2010.
- American College of Cardiology Foundation