Influence of cardiovascular co-morbidities on the in-hospital mortality among patients with sickle cell crisis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Influence of cardiovascular co-morbidities on the in-hospital mortality among patients with sickle cell crisis Sam J. Wu, Muhammad Yousuf, Muhammad Khubaib Gul Khan, Jugraj Singh, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8099349/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 7 You are reading this latest preprint version Abstract Using the US National Inpatient Sample, we analyzed 424,540 adult hospitalizations for sickle cell crisis (SCC) from 2016–2020 to quantify cardiovascular comorbidities and their associations with in-hospital mortality. The cohort (mean age 32.4 years; 55.4% female) was predominantly Black (93.0%) and socioeconomically disadvantaged (51.1% lowest income quartile); most admissions occurred at urban teaching hospitals (82.1%). Age showed a monotonic relation with mortality (multivariable HR per year 1.04, 95% CI 1.03–1.05). In adjusted models, six cardiovascular factors independently predicted higher mortality: systolic heart failure (HR: 2.0; 1.35–2.96), atrial fibrillation/flutter (HR: 1.58; 1.08–2.30), ischemic stroke (HR: 3.25; 1.85–5.71), right ventricular failure (HR: 3.14; 1.46–6.75), pulmonary embolism (HR: 5.61; 3.78–8.33) and acute coronary syndrome (HR: 3.70; 2.30–5.95) (All p<0.01). By contrast, chronic coronary artery disease was inversely associated with mortality (adjusted OR 0.41, 0.23–0.74, p<0.01), a paradoxical pattern that likely reflects index-event (collider) bias, treatment confounding, or differential specialty follow-up and warrants prospective adjudication. Compared with White patients, Black patients had lower adjusted in-hospital mortality (HR 0.44, 0.21–0.94, p = 0.03). Our findings prioritize thrombo-ischemic and rhythm/pump failure phenotypes as high-yield targets for risk stratification and crisis-time management, and they motivate integrated cardio-hematologic strategies and prospective validation. Sickle cell disease sickle cell crisis cardiovascular comorbidities Figures Figure 1 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 28 Jan, 2026 Reviews received at journal 23 Jan, 2026 Reviewers agreed at journal 09 Dec, 2025 Reviewers invited by journal 05 Dec, 2025 Editor assigned by journal 24 Nov, 2025 Submission checks completed at journal 24 Nov, 2025 First submitted to journal 12 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8099349","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":555903232,"identity":"77840bfb-84e5-4a26-be07-aced1c959aa7","order_by":0,"name":"Sam J. 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