Comprehensive cardiovascular outcomes in patients with sickle cell disease: real life evidence from a large collaborative network

Sickle cell disease (SCD) significantly reduces life expectancy. While cardiovascular disease (CVD) is a major contributor, comprehensive contemporary cardiovascular risk assessment remains understudied. This retrospective cohort study utilized the TrinetX US Collaborative Research Network- a large multisystem database comprising over 100 million patients, analyzing data from adults aged 30–60. Propensity score matching (PSM) was employed to compare cardiovascular outcomes in SCD patients with a matched non-SCD cohort. The primary outcome examined was comparing the prevalence of ischemic heart disease (IHD). Secondary outcomes included aortic stenosis, aortic insufficiency, mitral and tricuspid insufficiency, arrhythmias including atrial fibrillation, atrial flutter, and ventricular tachycardia. After performing propensity score matching, our study included 33,249 patients in each group of both the SCD and non-SCD cohorts. Both cohorts were predominantly composed of Black and female patients, with a mean age of 34.6 in the SCD cohort and 35.2 in the non-SCD cohort. The cohorts were well-matched for demographics and traditional CVD risk factors. The SCD cohort had a significantly higher risk of the primary outcome, ischemic heart disease (IHD) (RR 1.7; 95% CI 1.6–1.8). Secondary outcomes with elevated risk in the SCD cohort included heart failure (RR 2.1; 95% CI 2.0–2.3), tricuspid regurgitation (RR 2.7; 95% CI 2.4–3.0), pulmonary hypertension (RR 5.3; 95% CI 4.8–5.8), stroke (RR 3.2; 95% CI 2.9–3.6), ventricular tachycardia (RR 1.6; 95% CI 1.3–1.9), mitral valve stenosis (RR 2.1; 95% CI 1.5–3.1), aortic insufficiency (RR 1.7; 95% CI 1.5–2.1), atrial fibrillation (RR 1.5; 95% CI 1.4–1.6), atrial flutter (RR 1.4; 95% CI 1.1–1.7), and dilated cardiomyopathy (DCM) (RR 1.5; 95% CI 1.2–1.8). Survival analysis: At the end of the study period, the SCD cohort had a lower survival probability (75.37%) compared to the non-SCD cohort (87.83%), with 1757 deaths in the SCD group versus 1121 in the non-SCD group (risk ratio for death: 1.6; 95% CI 1.5–1.7). This study provides strong evidence for an elevated CVD burden in SCD patients. The results underscore the need for further research to elucidate the mechanisms underlying these increased cardiovascular risks and to develop targeted prevention and intervention strategies for this patient population.