Ali, Meher

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.