# Circulating biomarkers and mortality in atrial fibrillation: the REasons for Geographic And Racial Differences in Stroke study

## TL;DR

This study identifies several biomarkers linked to higher mortality in people with atrial fibrillation, highlighting potential targets for reducing risk.

## Contribution

The study provides novel evidence on circulating biomarkers associated with mortality in atrial fibrillation patients.

## Key findings

- Multiple biomarkers, such as N-terminal pro B-type natriuretic peptide and interleukin-6, were strongly associated with all-cause mortality in AF patients.
- Most biomarkers showed stronger associations with cardiovascular mortality compared to cancer mortality.
- Biomarker associations were consistent across racial groups in the study population.

## Abstract

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 US national biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

REGARDS enrolled 30 239 Black and White adults aged ≥45 in 2003–07. Candidate biomarkers were measured in all participants with baseline AF and no prior stroke (n = 2260) and deaths identified through 31 December 2019. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause, cardiovascular-, and cancer-related mortality by biomarker levels. The mean baseline age was 67.5 years. Participants were 53.5% female, 35.7% identified as Black, and 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 fourth vs. first 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.

Several biomarkers were associated with all-cause and cardiovascular mortality in AF, suggesting multiple domains of clinical relevance that support interventions to reduce mortality.