Background:

Sickle cell crisis (SCC) remains a leading cause of emergency hospitalization and acute morbidity in patients with sickle cell disease (SCD). With improved survival in SCD, long-term complications such as cardiovascular disease are emerging as critical determinants of morbidity and mortality. While right-sided heart failure has been adequately explored in SCD, the specific contribution of the other cardiovascular conditions to in-hospital mortality during sickle cell crisis remains unclear. This study evaluates the independent impact of cardiovascular comorbidities on in-hospital mortality among adults hospitalized for SCC using a large, nationally representative database.

Methods:

This is a retrospective analysis involving adult hospitalizations (≥ 18 years old) for SCC in the United States (U.S) using 2016-2020 National Inpatient Sample (NIS). The study was exempt from institutional review board approval as the NIS database contains deidentified patient information. ICD-10 codes used for SCC were: D570, D5721, D5741, D5743, D5745, D5781. Regarding cardiovascular co-morbidities, the study considered age, race (African American, Hispanic and Caucasian), dyslipidemia, hypertension, diabetes mellitus (both type 1 and type 2), systolic and diastolic heart failure, rheumatic valvular heart disease, atrial fibrillation/flutter, pulmonary hypertension, chronic coronary artery disease and ischemic stroke. Univariable Cox regression was performed to identify independent predictors associated with in-hospital mortality among patients admitted for SCC. All factors from the univariable analysis with p<0.20 were included in a multivariable Cox regression model. All the outcomes were adjusted for age, sex, and Charlson Comorbidity Index. P-value of ≤0.05 was used to determine statistical significance.

Results:

The current study analyzed 424,540 SCD patients admitted for SCC (mean age 32.4 years, 55.4% females), from 2016 to 2020. Each additional year of age beyond 18 was associated with a linearly increasing in-hospital mortality among study patients hospitalized for SCC. This observation was confirmed in both univariate (HR: 1.06, 95% CI: 1.05–1.07, p<0.001) and multivariate (HR: 1.05, 95% CI: 1.04–1.06, p<0.001) analyses.

On univariable analysis of cardiovascular co-morbidities in patients admitted for SCC, a higher in-hospital mortality was conferred by: hypertension (HR: 2.40; 1.95 – 2.94, p <0.01) dyslipidemia (HR: 2.38; 1.54 – 3.65, p <0.01), diabetes mellitus (HR: 2.15; 1.51 – 3.04, p <0.01, systolic (HR: 5.20; 3.70 – 7.31, p <0.01) and diastolic heart failure (HR: 2.11; 1.44 – 3.08, p <0.01), atrial fibrillation/flutter (HR: 5.43; 4.04 – 7.32, p <0.01), pulmonary hypertension (HR: 2.34; 1.75 – 3.13, p <0.01) and ischemic stroke (HR: 5.75; 3.30 – 10.03, <0.01); a lower in-hospital mortality was associated with the African American race (HR: 0.43; 0.20 – 0.91, p = 0.027).

In multivariable analysis of cardiovascular comorbidities that demonstrated nominal significance (p < 0.20) in univariable analysis, only the following remained significantly associated with in-hospital mortality: systolic heart failure (HR: 2.65; 1.77 – 3.98, p <0.01), atrial fibrillation/flutter (HR: 2.01; 1.41 – 2.8), p <0.01) and ischemic stroke (HR: 3.25; 1.85 – 5.71, p <0.01). Although not statistically significant in univariable analysis (p = 0.065), chronic coronary artery disease (CAD) emerged as a significant predictor of reduced in-hospital mortality in the multivariable analysis (HR: 0.52; 0.29–0.91, p = 0.021).

Conclusions:

Among adults hospitalized for sickle cell crises, select cardiovascular comorbidities, including systolic heart failure, atrial fibrillation/flutter, and ischemic stroke, were independently associated with significantly increased in-hospital mortality. Interestingly, CAD was linked to reduced mortality in adjusted models. This may be attributed to closer medical surveillance and management in patients with established CAD, along with the potential protective mechanism(s) in SCD that limit atherosclerotic progression — warranting further investigation

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2025
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