Comprehensive assessment of novel cardiovascular biomarkers in AF

Background and aims Biomarkers have the potential to improve risk prediction beyond clinical characteristics. We examined the association of four emerging cardiovascular biomarkers (angiopoietin 2 [Angpt2], bone morphogenetic protein 10 [BMP10], fibroblast growth factor 23 [FGF23], insulin-like growth factor binding protein 7 [IGFBP7]) in comparison with N-terminal pro B-type natriuretic peptide (NTproBNP) across the disease course of atrial fibrillation (AF). Methods We enrolled patients from a prospective cohort of patients at risk of AF or with manifest arrhythmia. The circulating vascular biomarkers were quantified using high-throughput, high-precision precommercial assays (Roche Diagnostics). A combined endpoint comprised: stroke, transient ischemic attack (TIA), myocardial infarction, incident coronary heart disease, heart failure and all-cause mortality. Results Of total N=1,047 individuals, N=527 had prevalent AF, N=507 were free of AF at baseline. Median follow-up was 42 months. A total of N=66 individuals died; the combined endpoint occurred in N=198 individuals. All five biomarkers were significantly associated with the incidence of AF both, in multi-state analysis (MSA) and Cox regression, though the association with FGF23 was only significant in the age and sex adjusted Cox model. AF recurrence was significantly associated with all biomarkers, most strongly with NTproBNP. In prevalent AF, NTproBNP, FGF23 and IGFBP7 were associated with the combined endpoint and all-cause mortality, Angpt2 was associated with all-cause mortality. NTproBNP showed the strongest association for all-cause mortality, IGFBP7 for the combined endpoint in prevalent AF. In incident AF the association with the combined outcome was statistically significant for NTproBNP in multivariable-adjusted models. All-cause mortality in individuals with incident AF was associated with NTproBNP, Angpt2, FGF23 and IGFBP7 both in the MSA and Cox model. Conclusions All novel biomarkers Angpt2, BMP10, FGF23 and IGFBP7 showed predictive value for incident and recurrent AF. Individual biomarkers showed distinct strengths in prediction of outcomes across the disease spectrum of AF.