Circulating biomarkers and ischemic stroke risk in adults with atrial fibrillation taking anticoagulation: the Reasons for Geographic And Racial Differences in Stroke study

Abstract

Background: Anticoagulation reduces ischemic stroke risk in atrial fibrillation (AF), but "breakthrough" stroke occurs. Blood biomarkers might help identify patients at risk for this, but existing studies are limited in examining few biomarkers in select populations.

Objectives: To determine whether established biomarkers of ischemic stroke risk will be associated with ischemic stroke risk in people with AF on anticoagulation sampled from the general population.

Methods: The REasons for Geographic and Racial Differences in Stroke study is a prospective cohort study of 30 239 Black or White adults aged ≥45 years at enrollment in 2003 to 2007 monitored for stroke. Nine biomarkers were measured at baseline in participants with AF, no prior stroke, and who were taking oral anticoagulation at baseline. Hazard ratios of ischemic stroke were estimated by Cox models adjusted for demographics and stroke risk factors.

Results: Among 713 participants with AF on warfarin (median age 76, 36% female, 17% Black), 67 (9%) developed a first-time ischemic stroke over 12 years. Adjusting for confounders, each SD higher N-terminal pro-B-type natriuretic peptide (NTproBNP), factor VIII, D-dimer, and growth differentiation factor 15 (GDF-15) were positively associated with incident stroke, with hazard ratios ranging from 1.49 (95% CI, 1.11-2.02) for NTproBNP to 1.28 (95% CI, 0.92-1.77) for GDF-15. Associations for D-dimer and GDF-15 did not meet statistical significance.

Conclusion: Biomarkers of atriopathy, coagulation, and vascular inflammation were associated with higher ischemic stroke risk in people with AF on anticoagulation at baseline. Findings highlight new avenues for reducing stroke risk in AF, but a larger study is needed for validation.

Keywords: anticoagulant; atrial fibrillation; biomarkers; cohort study; ischemic stroke.