Abstract 54: Circulating Biomarkers and Anticoagulation Breakthrough Stroke Risk in Atrial Fibrillation: The REGARDS Study

Introduction: Anticoagulation reduces ischemic stroke risk in atrial fibrillation (AF), but “breakthrough” stroke occurs. Blood biomarkers might help identify patients at risk for anticoagulation breakthrough stroke, but existing studies are limited by examining few biomarkers in select populations. Hypotheses: Established biomarkers of ischemic stroke risk will also be associated with ischemic stroke risk in people with AF on anticoagulation sampled from the general population. Methods: REGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 on enrollment in 2003-7 monitored for stroke. Nine established blood biomarkers of ischemic stroke risk were measured at baseline in participants with AF and with no prior stroke 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 anticoagulation (median age 76, 36% female, 17% Black, all taking vitamin K antagonists), 67 (9%) developed a first-time ischemic stroke over 12 years. In models adjusted for demographics, there were positive associations of all biomarkers with stroke risk except for galectin-3, lipoprotein(a), and cystatin C which had inverse or null associations (Figure). Adjustment for risk factors minimally impacted interpretation of results. The greatest associations were with higher N-terminal pro-B type natriuretic peptide, factor VIII, D-dimer, and growth differentiation factor 15; associations for D-dimer and growth differentiation factor 15 were not statistically significant. Hazards for galectin-3, gamma glutamyl transferase, interleukin 6, and lipoprotein (a) were modest and not statistically significant. Conclusion: Biomarkers of cardiac strain (specifically atriopathy), coagulation, and 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.