Gastrointestinal Bleeding Risk Associated With Pulse Pressure in Patients With Atrial Fibrillation: A Retrospective Cohort Study (Preprint)

Background: Anticoagulated patients with atrial fibrillation (AF) face significant bleeding risks, which current risk scores inadequately predict. Pulse pressure (PP), a marker of arterial stiffness, may offer additional prognostic value. Objective: This study aimed to evaluate whether elevated PP independently predicts major bleeding events. Methods: We conducted a retrospective cohort study using electronic health records from 4,935 AF patients on oral anticoagulation (2010–2019) in the REACHnet network. PP was calculated from outpatient blood pressure readings and analyzed in tertiles and as a continuous variable. Kaplan-Meier curve and log-rank test were conducted to assess the association between PP and clinical outcomes. Cox regression models further adjusted for demographics, comorbidities, systolic blood pressure, medications, and the ORBIT bleeding score. Results: Over a median 5-year follow-up, 677 patients (13.7%) experienced major bleeding. GI bleeding was significantly more frequent in the highest PP tertile (p = 0.007), while intracranial and other bleeding types showed no significant differences. Each 10 mmHg increase in PP was associated with a 15% higher risk of GI bleeding (HR: 1.014; p = 0.042), and this association remained significant after adjusting for systolic blood pressure and the ORBIT score (OR: 1.013 per mmHg; p = 0.028). PP was not significantly associated with intracranial, other, or overall bleeding. Conclusions: Pulse pressure independently predicts gastrointestinal bleeding in anticoagulated AF patients, even after accounting for traditional bleeding risk factors. These findings support the inclusion of PP in future risk stratification models and clinical monitoring strategies. Clinical Trial: N/A