{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:43:11Z","timestamp":1785544991636,"version":"3.56.0"},"reference-count":40,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Internet Res"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n 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\u201062, 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\n ICD-9<\/jats:italic>\n \/\n ICD-10<\/jats:italic>\n 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\n P<\/jats:italic>\n <.05.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 (\n P=<\/jats:italic>\n .007). Kaplan-Meier analysis confirmed lower gastrointestinal bleeding-free survival in the highest tertile (log-rank\n P=<\/jats:italic>\n .004). No significant differences were observed for intracranial (\n P=<\/jats:italic>\n .08), other (\n P<\/jats:italic>\n =.58), or composite bleeding (\n P<\/jats:italic>\n =.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\u20101.028;\n P=<\/jats:italic>\n .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\u20101.025;\n P<\/jats:italic>\n =.03), while SBP was not independently significant (\n P<\/jats:italic>\n =.13).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.2196\/93347","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T07:00:10Z","timestamp":1779260410000},"page":"e93347-e93347","source":"Crossref","is-referenced-by-count":0,"title":["Gastrointestinal Bleeding Risk Associated With Pulse Pressure in Patients With Atrial Fibrillation: Retrospective Cohort Study"],"prefix":"10.2196","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2038-7678","authenticated-orcid":false,"given":"Michel","family":"Abou Khalil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-8772","authenticated-orcid":false,"given":"Carlo","family":"El Khoury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2026-2912","authenticated-orcid":false,"given":"Yishi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0148-0080","authenticated-orcid":false,"given":"Maximilian","family":"Moersdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3441-0617","authenticated-orcid":false,"given":"Christian","family":"Massad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5954-3445","authenticated-orcid":false,"given":"Alex","family":"El Darzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4304-603X","authenticated-orcid":false,"given":"Yara","family":"Menassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2046-209X","authenticated-orcid":false,"given":"Mohammad Montaser","family":"Atasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3562-7386","authenticated-orcid":false,"given":"Ghassan","family":"Bidaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-1164","authenticated-orcid":false,"given":"Hadi","family":"Younes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-798X","authenticated-orcid":false,"given":"Ala","family":"Assaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-5419","authenticated-orcid":false,"given":"Mario","family":"Mekhael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2542-941X","authenticated-orcid":false,"given":"Eli","family":"Tsakiris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9998-5601","authenticated-orcid":false,"given":"Chanho","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3179-4398","authenticated-orcid":false,"given":"Charbel","family":"Noujaim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4263-9553","authenticated-orcid":false,"given":"Abboud","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3288-0902","authenticated-orcid":false,"given":"Yingshuo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-3853","authenticated-orcid":false,"given":"Mary Margot M","family":"Maleckar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5957-4637","authenticated-orcid":false,"given":"Rodolfo A","family":"Montiel Quintero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6189-2821","authenticated-orcid":false,"given":"Omar","family":"Kreidieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-7023","authenticated-orcid":false,"given":"Amitabh C","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-8931","authenticated-orcid":false,"given":"Han","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-4584","authenticated-orcid":false,"given":"Qussay","family":"Marashly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0454-0541","authenticated-orcid":false,"given":"Nassir F","family":"Marrouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1010","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"2","key":"R1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euaf027","article-title":"Global, regional, and national burden of atrial fibrillation and atrial flutter from 1990 to 2021: sex differences and global burden projections to 2046-a systematic analysis of the Global Burden of Disease Study 2021","volume":"27","author":"Tan","journal-title":"Europace"},{"issue":"4","key":"R2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euae070","article-title":"Longer and better lives for patients with atrial fibrillation: the 9th AFNET\/EHRA consensus conference","volume":"26","author":"Linz","journal-title":"Europace"},{"issue":"2","key":"R3","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/ehjqcco\/qcaa093","article-title":"Atrial fibrillation in the UK: predicting costs of an emerging epidemic recognizing and forecasting the cost drivers of atrial fibrillation-related costs","volume":"8","author":"Burdett","journal-title":"Eur Heart J Qual Care Clin Outcomes"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5058","article-title":"Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis","volume":"359","author":"L\u00f3pez-L\u00f3pez","journal-title":"BMJ"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.11.025","article-title":"Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study","volume":"254","author":"Chao","journal-title":"Int J Cardiol"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2026.04.001","article-title":"Identifying risk factors for major bleeding in patients with atrial fibrillation using direct oral anticoagulants: a systematic review and meta-analysis","author":"Wang","journal-title":"J Thromb Haemost"},{"issue":"10","key":"R7","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1002\/clc.22294","article-title":"Stroke and bleeding risk in atrial fibrillation: navigating the alphabet soup of risk-score acronyms (CHADS2, CHA2 DS2 -VASc, R2 CHADS2, HAS-BLED, ATRIA, and more)","volume":"37","author":"Dzeshka","journal-title":"Clin Cardiol"},{"issue":"4","key":"R8","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/s0735-1097(01)01108-1","article-title":"Pulse pressure--a review of mechanisms and clinical relevance","volume":"37","author":"Dart","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"R9","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.jtha.2025.07.040","article-title":"A comparative analysis of HAS-BLED, ORBIT, DOAC, and AF-BLEED bleeding-risk scores in anticoagulated patients with atrial fibrillation: a report from the prospective Murcia Atrial Fibrillation Project III (MAFP-III) cohort","volume":"24","author":"Soler-Espejo","journal-title":"J Thromb Haemost"},{"issue":"5","key":"R10","doi-asserted-by":"publisher","DOI":"10.1002\/clc.70315","article-title":"DOAC score versus HAS-BLED and ORBIT for predicting bleeding events in atrial fibrillation on direct oral anticoagulants","volume":"49","author":"Guo","journal-title":"Clin Cardiol"},{"issue":"7","key":"R11","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1001\/jama.281.7.634","article-title":"Increased pulse pressure and risk of heart failure in the elderly","volume":"281","author":"Chae","journal-title":"JAMA"},{"issue":"8","key":"R12","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s00392-016-0972-2","article-title":"Pulse pressure as an independent predictor of stroke: a systematic review and a meta-analysis","volume":"105","author":"Liu","journal-title":"Clin Res Cardiol"},{"issue":"7","key":"R13","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1001\/jama.297.7.709","article-title":"Pulse pressure and risk of new-onset atrial fibrillation","volume":"297","author":"Mitchell","journal-title":"JAMA"},{"issue":"9","key":"R14","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1097\/HJH.0000000000003223","article-title":"Arterial stiffness and atrial fibrillation: shared mechanisms, clinical implications and therapeutic options","volume":"40","author":"Vio","journal-title":"J Hypertens"},{"issue":"3","key":"R15","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.022317","article-title":"Elevated pulse pressure and recurrent hemorrhagic stroke risk in stroke with cerebral microbleeds or intracerebral hemorrhage","volume":"11","author":"Park","journal-title":"J Am Heart Assoc"},{"issue":"11","key":"R16","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1093\/ajh\/hpx135","article-title":"Hypertension and atrial fibrillation: balancing stroke and bleeding risks","volume":"30","author":"Esteve-Pastor","journal-title":"Am J Hypertens"},{"issue":"1","key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.102285","article-title":"Risk scores for major bleeding from direct oral anticoagulants: comparing predictive performance in patients with atrial fibrillation","volume":"8","author":"Campos-Staffico","journal-title":"Res Pract Thromb Haemost"},{"issue":"2","key":"R18","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/s41440-025-02441-3","article-title":"Optimal blood pressure levels for patients with atrial fibrillation who are on undergoing anticoagulant therapy: a large-scale real-world data (F-CREATE project)","volume":"49","author":"Ishida","journal-title":"Hypertens Res"},{"key":"R19","unstructured":"US Department of Health and Human Services, Office for Human Research Protections. Protection of human subjects 45 CFR \u00a746 title 45\u2014public welfare, part 46, subpart a (basic HHS policy for protection of human research subjects). Electronic Code of Federal Regulations. URL: https:\/\/www.ecfr.gov\/current\/title-45\/subtitle-A\/subchapter-A\/part-46\/subpart-A\/section-46.101 [Accessed 12-06-2026]"},{"issue":"5","key":"R20","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1378\/chest.10-0134","article-title":"A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey","volume":"138","author":"Pisters","journal-title":"Chest"},{"issue":"12","key":"R21","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1038\/s41440-023-01361-4","article-title":"Anticoagulant therapy and home blood pressure-associated risk for stroke\/bleeding events in elderly patients with non-valvular atrial fibrillation: the sub-cohort study of ANAFIE registry","volume":"46","author":"Kario","journal-title":"Hypertens Res"},{"issue":"3","key":"R22","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1161\/HYP.0000000000000033","article-title":"Recommendations for improving and standardizing vascular research on arterial stiffness: a scientific statement from the American Heart Association","volume":"66","author":"Townsend","journal-title":"Hypertension"},{"issue":"9","key":"R23","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1016\/j.jacc.2019.07.012","article-title":"Large-artery stiffness in health and disease: JACC state-of-the-art review","volume":"74","author":"Chirinos","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"R24","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.jacc.2015.10.084","article-title":"Pulse pressure and risk for cardiovascular events in patients with atherothrombosis: from the REACH registry","volume":"67","author":"Selvaraj","journal-title":"J Am Coll Cardiol"},{"issue":"21","key":"R25","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1016\/j.jacc.2015.09.024","article-title":"Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF trial","volume":"66","author":"Sherwood","journal-title":"J Am Coll Cardiol"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2021.01.020","article-title":"Frequency, trend, predictors, and impact of gastrointestinal bleeding in atrial fibrillation hospitalizations","volume":"146","author":"Dave","journal-title":"Am J Cardiol"},{"issue":"1","key":"R27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-59932-5","article-title":"Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis","volume":"14","author":"Yamamoto","journal-title":"Sci Rep"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaf300","article-title":"Risk factors associated with gastrointestinal bleeding in patients with cardiovascular disease (INTERBLEED): a case control study","volume":"32","author":"Bosch","journal-title":"Eur J Prev Cardiol"},{"issue":"1","key":"R29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21926\/obm.neurobiol.2201117","article-title":"Arterial elasticity: linking of cardiovascular risks, pulse pressure, dementia, aging, and drug targeting","volume":"06","author":"D\u2019Arrigo","journal-title":"OBM Neurobiol"},{"issue":"3","key":"R30","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/cphy.c150007","article-title":"The gastrointestinal circulation: physiology and pathophysiology","volume":"5","author":"Granger","journal-title":"Compr Physiol"},{"issue":"7","key":"R31","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1161\/STROKEAHA.121.036885","article-title":"Review of long-term blood pressure control after intracerebral hemorrhage: challenges and opportunities","volume":"53","author":"Mullen","journal-title":"Stroke"},{"issue":"1","key":"R32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2025.e00526","article-title":"Individualized autoregulation-guided arterial blood pressure management in neurocritical care","volume":"22","author":"Gomez","journal-title":"Neurotherapeutics"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2021.11.027","article-title":"Cerebral pressure autoregulation in brain injury and disorders\u2014a review on monitoring, management, and future directions","volume":"158","author":"Svedung Wettervik","journal-title":"World Neurosurg"},{"issue":"3","key":"R34","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0002-9610(86)90465-4","article-title":"Colonic vascular ectasias and aortic stenosis: coincidence or causal relationship?","volume":"151","author":"Greenstein","journal-title":"Am J Surg"},{"issue":"5","key":"R35","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s11906-023-01238-4","article-title":"Effect of different classes of antihypertensive drugs on arterial stiffness","volume":"25","author":"Schettini","journal-title":"Curr Hypertens Rep"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.762586","article-title":"Antihypertensive treatment and central arterial hemodynamics: a meta-analysis of randomized controlled trials","volume":"12","author":"Cheng","journal-title":"Front Physiol"},{"issue":"1","key":"R37","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.atherosclerosis.2011.12.005","article-title":"Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials","volume":"221","author":"Shahin","journal-title":"Atherosclerosis"},{"issue":"11","key":"R38","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/s41371-022-00675-z","article-title":"Wearable blood pressure measurement devices and new approaches in hypertension management: the digital era","volume":"36","author":"Konstantinidis","journal-title":"J Hum Hypertens"},{"issue":"3","key":"R39","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1161\/HYPERTENSIONAHA.120.14742","article-title":"Management of hypertension in the digital era: small wearable monitoring devices for remote blood pressure monitoring","volume":"76","author":"Kario","journal-title":"Hypertension"},{"issue":"9","key":"R40","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/s41569-025-01127-0","article-title":"Wearable blood pressure sensors for cardiovascular monitoring and machine learning algorithms for blood pressure estimation","volume":"22","author":"Min","journal-title":"Nat Rev Cardiol"}],"container-title":["Journal of Medical Internet Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jmir.org\/2026\/1\/e93347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:23:44Z","timestamp":1785536624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jmir.org\/2026\/1\/e93347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":40,"URL":"https:\/\/doi.org\/10.2196\/93347","relation":{},"ISSN":["1438-8871"],"issn-type":[{"value":"1438-8871","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"v28i2e93347"}}