Biomarkers for Prediction of Atrial Fibrillation in European Cohorts

Introduction: Blood-based biomarkers are objective tools to assess susceptibility for atrial fibrillation (AF). Hypothesis: Whether novel biomarkers improve risk prediction based on clinical risk factors and N-terminal pro B-type natriuretic peptide (Nt-proBNP) remains to be shown. Methods: In individuals from two European community studies (N=32,318) we examined 11 circulating biomarkers representing lipids (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein A1, apolipoprotein B), inflammation (C-reactive protein), renal function (cystatin C), myocardial damage (high sensitivity assayed troponin I (hsTnI)), and vitamin D in relation to incidence of AF in addition to clinical risk factors and Nt-proBNP. Multivariable-adjusted Cox regression models were computed for models comprising classical cardiovascular risk factors and biomarkers. Net reclassification improvement (NRI) was computed. Results: The median age was 53.2 (interquartile range 44.0, 62.9) years, age range 24.1-97.6 years, 51.9% women. Over a median follow-up of 4.9 years N=893 AF cases occurred. In multivariable-adjusted models there was evidence for an association between one standard deviation increase in biomarker for total cholesterol (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.83-0.97;P=0.0042), LDL cholesterol (HR 0.89, 95% CI 0.82-0.96; P=0.0015), apolipoprotein B (HR 0.89, 95% CI 0.83-0.96; P=0.0033), cystatin C 1/3 (HR 1.19, 95% CI 1.11-1.28; P 1/3 (HR 1.09, 95% CI 1.04-1.13;P Conclusions: Several known and novel biomarkers including blood lipids (total and LDL cholesterol, lipoprotein B), hsTnI and cystatin C are related to incident AF in large European cohorts. None proved to be superior to Nt-proBNP in C-statistic and net reclassification analyses. A possible benefit in the clinical application of Nt-proBNP for AF risk prediction needs to be shown.