Introduction: Sickle cell disease (SCD) is one of the most common genetic disorders, it not only has hematological pathophysiological consequences, but also has systemic pathological manifestations such as vascular events. It is characterized by structurally abnormal hemoglobin (HbS) that polymerizes to "sickle" red blood cells under stress, most commonly due to hypoxia. SCD can lead to hemolysis and in turn causes endothelial dysfunction and sequestration of sickled cells which can result in cardiovascular or cerebrovascular events (VEs). Furthermore, increased expression of adhesion cellular signaling pathways of red blood cells and endothelial cells and endothelial damage further enhance vascular thrombotic events. Prior studies have described that VEs are associated with poor outcomes in the short term and decreased quality of life in patients over the long term. Data has been lacking in regards to the burden of these VEs in SCD from a population based study. We sought to estimate the trends, predictors and outcomes of VEs in SCD patients from a nationally representative database of the USA.

Methods: In this cross-sectional study, cohort on hospitalisations among SCD patients was extracted using International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM) from the National Inpatient Sample (NIS) for the years 2008-2017. We then identified the prevalence of cardiovascular events (ischemic heart disease) and cerebrovascular events (Ischemic and Hemorrhagic) by previously validated ICD-9/10-CM codes. We then created a composite variable of any VEs which included both cardiovascular and cerebrovascular events. Our primary objective was to delineate temporal trends, outcomes and predictors of VEs in SCD patients. We utilized Cochran Armitage trend test and multivariable survey logistic regression models to analyze the trends, predictors and outcomes.

Results: Out of a total 1,250,424 hospitalizations among SCD patients, 44,358 (3.6%) had any VEs. Prevalence of any VEs increased from 2.6% in 2008 to 4.3% in 2017 (pTrend<0.001) with yearly increment of 3% (OR 1.03; 95%CI 1.01-1.04; p<0.0001) after taking into account the changes in demographics and comorbidities. Patients who developed any VEs were older (48 vs 28-years; p<0.001), more likely in male (47% vs 44%; p<0.001). Furthermore, in multivariable regression analysis, increasing age (OR 1.7; 95%CI 1.7-1.8; p<0.0001); males (OR 1.4; 95%CI 1.3-1.5;p<0.0028); Caucacian (OR 1.7; 95%CI 1.5-2.0;p<0.001); hypertension (OR 2.2; 95%CI 2.1-2.4; p<0.0001); Obesity (OR 1.4; 95%CI 1.3-1.6; p<0.0001); psychiatric disorders (OR 1.5; 95%CI 1.3-1.7; p<0.0001) and diabetes (OR 1.7; 95%CI 1.6-1.9; p<0.0001) were associated with higher odds of VEs. Additionally, VEs were associated with higher in-hospital mortality (aOR 3.1; 95%CI 2.6-3.7; p<0.001) and discharge to facility (aOR 2.3; 95%CI 2.0-2.4; p<0.001) after adjusting with confounders and trends remained stable over the years.

Conclusion: We observed the incremental prevalence of VEs amongst SCD patients. We were able to identify the patients susceptible to VEs, most commonly occurring in older and male gender. VEs were associated with significantly poor outcomes as noted by higher in-hospital mortality and discharge to facility centers. Further studies are required to delineate the strategies for early identification, better risk stratifications and prevention in order to improve the quality of life in SCD patients and decrease mortality. We should also vigorously control other independent factors such as HTN, DM and obesity to decrease vascular events.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.