Multiple biomarkers and atrial fibrillation in the general population

PLoS One. 2014 Nov 17;9(11):e112486. doi: 10.1371/journal.pone.0112486. eCollection 2014.


Background: Different biological pathways have been related to atrial fibrillation (AF). Novel biomarkers capturing inflammation, oxidative stress, and neurohumoral activation have not been investigated comprehensively in AF.

Methods and results: In the population-based Gutenberg Health Study (n = 5000), mean age 56 ± 11 years, 51% males, we measured ten biomarkers representing inflammation (C-reactive protein, fibrinogen), cardiac and vascular function (midregional pro adrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [Nt-proBNP], sensitive troponin I ultra [TnI ultra], copeptin, and C-terminal pro endothelin-1), and oxidative stress (glutathioneperoxidase-1, myeloperoxidase) in relation to manifest AF (n = 161 cases). Individuals with AF were older, mean age 64.9 ± 8.3, and more often males, 71.4%. In Bonferroni-adjusted multivariable regression analyses strongest associations per standard deviation increase in biomarker concentrations were observed for the natriuretic peptides Nt-proBNP (odds ratio [OR] 2.89, 99.5% confidence interval [CI] 2.14-3.90; P<0.0001), MR-proANP (OR 2.45, 99.5% CI 1.91-3.14; P<0.0001), the vascular function marker MR-proADM (OR 1.54, 99.5% CI 1.20-1.99; P<0.0001), TnI ultra (OR 1.50, 99.5% CI 1.19-1.90; P<0.0001) and. fibrinogen (OR 1.44, 99.5% CI 1.19-1.75; P<0.0001). Based on a model comprising known clinical risk factors for AF, all biomarkers combined resulted in a net reclassification improvement of 0.665 (99.3% CI 0.441-0.888) and an integrated discrimination improvement of >13%.

Conclusions: In conclusion, in our large, population-based study, we identified novel biomarkers reflecting vascular function, MR-proADM, inflammation, and myocardial damage, TnI ultra, as related to AF; the strong association of natriuretic peptides was confirmed. Prospective studies need to examine whether risk prediction of AF can be enhanced beyond clinical risk factors using these biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Fibrillation / epidemiology*
  • Atrial Fibrillation / metabolism*
  • Biomarkers
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Statistical
  • Population Surveillance
  • Risk Factors


  • Biomarkers

Grants and funding

The Gutenberg Health Study is funded through the government of Rheinland-Pfalz (“Stiftung Rheinland Pfalz für Innovation”, contract number AZ 961-386261/733), the research programs “Wissenschafft Zukunft” and “Schwerpunkt Vaskuläre Prävention” of the Johannes Gutenberg-University of Mainz and its contract with Boehringer Ingelheim and PHILIPS Medical Systems including an unrestricted grant for the Gutenberg Health Study. This work was further supported by research grants from the Brandenburg Ministry of Economics, Germany, and the European Regional Development Fund (EFRE/ERDF). The test kits for Copeptin, Ct-pro-endothelin-1, MR-proADM, and MR-proANP were provided by B.R.A.H.M.S, Hennigsdorf, and for Nt-proBNP by Roche Diagnostics, Mannheim at no cost. Dr. Schnabel is supported by Deutsche Forschungsgemeinschaft (German Research Foundation) Emmy Noether Program SCHN 1149/3-1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.