Circulating Biomarkers and Mortality in Atrial Fibrillation: The REasons for Geographic And Racial Differences in Stroke Study

Abstract Background and aims Examination of biomarkers associated with mortality among people with atrial fibrillation (AF) may help identify possible preventive interventions in this high-risk population. We aimed to study associations of circulating biomarkers with all-cause and cause-specific mortality in persons with AF in the United States national biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Methods REGARDS enrolled 30,239 Black and White adults aged ≥45 in 2003-7. Candidate biomarkers were measured in all participants with baseline AF and no prior stroke (n=2260), and deaths identified through December 31, 2019. We calculated hazard ratios (HRs) with 95% confidence intervals (CI) for all-cause, cardiovascular-, and cancer-related mortality by biomarker levels. Results The mean baseline age was 67.5 years. Participants were 53.5% female, 35.7% identified as Black, 21.3% were taking an anticoagulant. Over 10.3 years, 1151 participants died (38.7% of cardiovascular disease, 16.1% of cancer). In multivariable-adjusted analyses, all analysed biomarkers except lipoprotein (a) were associated with all-cause mortality (HR, 95% CI for 4th vs 1st quartile): N-terminal pro B-type natriuretic peptide (4.85; 3.70-6.36), galectin-3 (2.03; 1.65-2.51), growth differentiation factor 15 (3.98; 3.00-5.29), cystatin C (2.81; 2.21-3.58), interleukin-6 (2.61; 2.08-3.26), D-dimer (1.74; 1.40-2.15), γ-glutamyltransferase (1.46; 1.21-1.76) and factor VIII antigen (2.03; 1.65-2.50). Most biomarker associations were stronger for cardiovascular than cancer mortality and did not differ by race. Conclusion Several biomarkers were associated with all-cause and cardiovascular mortality in AF, suggesting multiple domains of clinical relevance that support interventions to reduce mortality.