Prediabetes and Risk of Recurrent Ischemic Stroke in Atrial Fibrillation: A Propensity-Matched Cohort Study

<ns3:p>Background Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, yet the independent contribution of prediabetes to recurrent ischemic stroke risk in AF patients with prior cerebrovascular events remains poorly defined. Prior cross-sectional studies have yielded conflicting results, and no large propensity-matched investigation has examined longitudinal time-to-event outcomes in this population. Methods Using the TriNetX US Collaborative Network (67 healthcare organizations), adults with AF and prior ischemic stroke or transient ischemic attack were classified as having prediabetes (hemoglobin A1c 5.7%–6.4% or ICD-10 R73.03) or normoglycemia (hemoglobin A1c ≤5.6%). Patients with any form of diabetes mellitus were excluded. One-to-one propensity score matching balanced demographics and comorbidities. The primary outcome was recurrent ischemic stroke. Secondary outcomes included all-cause mortality, gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH). Cumulative risk and Kaplan-Meier survival analyses were performed. Results After matching, 80,335 patients per cohort were analyzed (mean age 70 years; 54.7% male; all standardized mean differences &lt;0.02). Cumulative recurrent stroke risk did not differ between groups (60.0% vs 60.4%; risk ratio 0.993, 95% CI 0.982–1.005; P = 0.264). Time-to-recurrence was significantly longer in the prediabetes cohort (median 1,794 vs 1,695 days; hazard ratio [HR] 0.960, 95% CI 0.943–0.978; P &lt; 0.001). Prediabetes was associated with lower all-cause mortality (HR 0.891, 95% CI 0.873–0.910; P &lt; 0.001) and lower GI bleeding (HR 0.918, 95% CI 0.889–0.947; P = 0.003). ICH did not differ significantly (HR 0.961, 95% CI 0.917–1.007; P = 0.065). Conclusions Prediabetes was not associated with increased recurrent stroke risk in AF patients with prior cerebrovascular events. The observed longer time-to-recurrence and lower mortality may reflect a metabolic surveillance effect warranting prospective confirmation.</ns3:p>