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.

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.

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