Gastrointestinal Bleeding Risk Associated With Pulse Pressure in Patients With Atrial Fibrillation: Retrospective Cohort Study.

Background: Patients with atrial fibrillation (AF) face significant bleeding risks, particularly those receiving oral anticoagulation; however, existing risk scores such as HAS-BLED and ORBIT demonstrate limited predictive accuracy. Pulse pressure (PP), calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure, is a noninvasive marker of arterial stiffness that has been associated with cardiovascular outcomes. However, PP has not been evaluated as a predictor of bleeding in this population. Objective: This study evaluated whether elevated PP independently predicts major bleeding events, overall and by subtype, in patients with AF after adjusting for established clinical risk factors. Methods: We conducted a retrospective cohort study using electronic health records from REACHnet, a PCORnet-affiliated clinical data network in Louisiana. A total of 4935 adults (mean age 63.7, SD 11.0 y; n=1606, 32.5% female) with AF between 2010 and 2019 were included via consecutive sampling of all eligible patients. PP was derived from outpatient blood pressure measurements closest to AF diagnosis and analyzed in tertiles (low: <46, middle: 46-62, high: >62 mm Hg) and continuously per 10 mm Hg. The primary outcome was time to the first bleeding event, a composite of gastrointestinal bleeding, intracranial hemorrhage, and other clinically significant bleeding, identified using ICD-9/ICD-10 codes. Kaplan-Meier survival curves with log-rank testing were used for univariable analysis. Multivariable Cox proportional hazards regression was adjusted for age, sex, race, comorbidities, medications, and the ORBIT score. A sensitivity analysis applied multivariable logistic regression additionally incorporating SBP. Statistical significance was set at P<.05. Results: Over a 5-year follow-up, 677 out of 4935 (13.7%) patients experienced a bleeding event (intracranial hemorrhage: n=60, 1.2%; gastrointestinal bleeding: n=195, 4.0%; and other bleeding: n=149, 3.0%). Gastrointestinal bleeding differed significantly across PP tertiles (P=.007). Kaplan-Meier analysis confirmed lower gastrointestinal bleeding-free survival in the highest tertile (log-rank P=.004). No significant differences were observed for intracranial (P=.08), other (P=.58), or composite bleeding (P=.22). In multivariable Cox regression, each 1 mm Hg increase in PP was independently associated with a 1.4% higher gastrointestinal bleeding risk (hazard ratio 1.014, 95% CI 1.001-1.028; P=.04), approximately 15% per 10 mm Hg. This remained significant after adjusting for SBP and ORBIT score (odds ratio 1.013/mm Hg, 95% CI 1.001-1.025; P=.03), while SBP was not independently significant (P=.13). Conclusions: PP independently predicts gastrointestinal bleeding risk in patients with AF beyond established clinical risk factors and validated bleeding risk scores. Unlike prior investigations that examined SBP or diastolic blood pressure components in isolation, this is the first study to identify PP as a predictor of gastrointestinal bleeding in this population. As a readily available, low-cost hemodynamic parameter derived from routine clinical measurements, PP could enhance existing risk stratification tools and inform more personalized bleeding risk management strategies in patients with AF.