Neuroglial Biomarkers for Risk Assessment of Ischemic Stroke and Other Cardiovascular Events in Patients With Atrial Fibrillation Not Receiving Oral Anticoagulation

Background Cardiac biomarkers improve risk prediction in patients with atrial fibrillation (AF). We recently demonstrated that the NFL (neuron-specific protein neurofilament light chain) was associated with ischemic stroke in patients with AF not receiving oral anticoagulation. The association of other neuroglial biomarkers reflecting brain injury (ie, GFAP [glial fibrillary acidic protein], total tau [tau], and UCHL1 [ubiquitin carboxy-terminal hydrolase L1]) with the risk of stroke and other cardiovascular outcomes in AF is unknown.Methods and Results Baseline plasma samples were available from 967 patients with AF not receiving oral anticoagulation treatment. Concentrations of NFL, GFAP, tau, and UCHL1 were determined with a Single Molecule Array kit (Simoa). Associations between baseline biomarker level, clinical characteristics, and outcomes (ischemic stroke, hospitalization for heart failure, and all-cause death) were analyzed with multivariable Cox regression adjusted for clinical characteristics and other biomarkers. Higher levels of all 4 neuroglial biomarkers were correlated with increasing age and female sex. During a median follow-up of 3.6 years, NFL was associated with increased risk of ischemic stroke (for a doubling in NFL, hazard ratio [HR], 1.27 [95% CI, 1.03-1.56]) and death (HR, 1.46 [95% CI, 1.25-1.70]). In adjusted analyses, GFAP, tau, and UCHL1were not associated with stroke or death. NFL, tau, and UCHL1 were significantly associated with hospitalization for heart failure.Conclusions In patients with AF not receiving oral anticoagulation, NFL was the only neuroglial biomarker significantly and independently associated with the risk of ischemic stroke and death. Further studies evaluating NFL for stroke risk assessment in patients with AF and the impact of contemporary oral anticoagulation treatment are warranted.