Adults with sickle cell trait had no significant difference in all-cause mortality (HR 0.88; 95% CI 0.70-1.11) or cardiopulmonary outcomes compared with propensity-matched controls.
Cohort (n=5,274)
Yes
Does sickle cell trait increase the risk of mortality and major cardiopulmonary events in adults?
In a large real-world cohort, sickle cell trait was not associated with increased cardiopulmonary morbidity or mortality, reinforcing its largely benign nature despite higher healthcare utilization.
Effect estimate: HR 0.88 (95% CI 0.70-1.11)
Abstract Rationale Sickle cell trait (SCT) affects up to 10% of African Americans and is often considered benign. However, recent data suggest increased vascular susceptibility, including risk for chronic kidney disease and venous thromboembolism. Unlike sickle cell disease (SCD), which is associated with cardiopulmonary complications and early mortality, the long-term impact of SCT on cardiovascular and pulmonary health remains poorly defined. This study aimed to evaluate cardiopulmonary outcomes in adults with SCT. Methods We conducted a retrospective cohort study using the TriNetX Research Network. Adults aged 18 years and older with SCT confirmed by hemoglobin electrophoresis were identified. Patients with SCD or pregnancy were excluded. After 1:1 propensity score matching for demographics and comorbidities, 2,637 patients were included in each group. Primary outcomes were all-cause mortality and major cardiopulmonary events (heart failure, pulmonary hypertension, myocardial infarction, stroke, arrhythmias, and respiratory failure). Secondary outcomes included renal events (acute kidney injury and end-stage renal disease), thromboembolic events (venous thromboembolism, pulmonary embolism, and deep vein thrombosis), and healthcare utilization (emergency department, hospitalization, and outpatient visits). Outcomes were analyzed using Kaplan-Meier survival estimates and Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Results There was no difference in all-cause mortality between SCT and controls (HR 0.88, 95% CI 0.70-1.11). Cardiopulmonary outcomes were comparable, including heart failure (0.99 0.84-1.16), stroke (0.98 0.77-1.25), pulmonary hypertension (0.87 0.68-1.11), right heart failure (0.86 0.47-1.57), myocardial infarction (0.92 0.71-1.20), atrial fibrillation (0.89 0.71-1.10), and ventricular tachycardia (1.08 0.73-1.60). Renal outcomes showed no difference for acute kidney injury (1.10 0.95-1.29) or end-stage renal disease (0.88 0.72-1.09). Thromboembolic risk was unchanged for venous thromboembolism (1.00 0.80-1.26), pulmonary embolism (1.20 0.91-1.58), and deep vein thrombosis (0.98 0.75-1.29). Hospitalizations were similar (0.97 0.88-1.08), though SCT carriers had higher emergency department visits (1.15 1.05-1.25) and outpatient visits (1.12 1.06-1.19). Conclusion In this large, real-world propensity-matched analysis, adults with SCT did not exhibit increased risk of cardiopulmonary morbidity, thromboembolic events, or mortality compared with controls. Despite stable physiologic outcomes, SCT carriers showed higher healthcare utilization, which may reflect subclinical morbidity, heightened patient vigilance, or provider bias in evaluation. These findings reinforce the largely benign nature of SCT in the general population but highlight the need for prospective studies to validate long-term outcomes. This abstract is funded by: None
Chaaban et al. (Fri,) conducted a cohort in Sickle cell trait (n=5,274). Sickle cell trait vs. Propensity-matched controls was evaluated on All-cause mortality (HR 0.88, 95% CI 0.70-1.11). Adults with sickle cell trait had no significant difference in all-cause mortality (HR 0.88; 95% CI 0.70-1.11) or cardiopulmonary outcomes compared with propensity-matched controls.
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