Classical Risk Factors for Ischemic Stroke are not Associated with Inpatient Post-Stroke Mortality in Sickle Cell Disease

https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106089Get rights and content

Abstract

Objectives

Sickle cell disease is a common haemoglobinopathy that significantly increases the risk of ischemic stroke. Because the risk factors for ischemic stroke onset and mortality in non-sickle cell disease patients have been largely elucidated, this paper aims to analyze risk factors for ischemic stroke mortality in sickle cell disease patients, which remain largely unknown.

Materials/Methods

The National Inpatient Sample database (2016–2017) was used to develop a multivariable regression model for risk quantification of known ischemic stroke risk factors for in-hospital mortality in ischemic stroke patients with and without sickle cell disease.

Results

Classical risk factors for ischemic stroke onset, including ischemic heart disease, carotid artery disease, lipidemias, hypertension, obesity, tobacco use, atrial fibrillation, personal or family history of stroke, congenital heart defects, congestive heart failure, cardiac valve disorder, peripheral vascular disease, and diabetes mellitus are associated with in-hospital mortality in non-sickle cell patients (p < 0.05). However, no significant association was found between these stroke risk factors and in-hospital mortality in sickle cell disease patients presenting with ischemic stroke (p > 0.05).

Conclusions

While the classical risk factors for stroke onset are associated with in-hospital mortality in non-sickle cell stroke patients, they are not associated with in-hospital mortality in sickle cell stroke patients.

Introduction

Ischemic strokes are a common complication in Sickle cell disease (SCD) patients, contributing to 7–11% of SCD-related deaths.1 The Cooperative Study of Sickle Cell Disease (CSSCD), the largest longitudinal study of SCD patients,2 found that children (ages 0–15) with SCD have a 333 times greater risk for ischemic stroke than children without SCD or heart disease.3 CSSCD also reported that potential risk factors for ischemic stroke among SCD patients include TIA, steady state Hb concentration, acute chest syndrome and systolic blood pressure.2,4

Because of the varied nature of stroke outcomes, in-hospital mortality is often used as a consistent and objective metric for disease severity.5 Recognized predictors of ischemic stroke, including age, history of stroke, Transient Ischemic Attack (TIA), ischemic heart disease, atrial fibrillation, diabetes mellitus, hypertension, hyperlipidemia, and smoking, have been shown to be prognostic of in hospital mortality among ischemic stroke patients.5, 6, 7 However, whether or not these same factors are predictive of in hospital mortality in SCD patients with ischemic stroke as well has yet to be well investigated.

Platt et al. named the following risk factors for stroke onset in SCD patients: fetal hemoglobin levels, renal insufficiency, acute chest syndrome, seizures and white blood cell count.8 However, whether those risk factors for ischemic stroke onset or other classical risk factors for ischemic stroke onset were predictive of in hospital mortality in SCD patients as well is not established. Hence, we conducted a large-scale analysis using the National Inpatient Sample (NIS) and American Stroke Association ischemic stroke risk factors9 to assess if SCD patients presenting with stroke have the same risk factors for in-hospital mortality as do non-SCD stroke patients.

Section snippets

Methods

Data was collected from the National Inpatient Sample (NIS) database for the years 2016 and 2017 and analyzed using Statistical Package for the Social Sciences (SPSS) version 25. Descriptive statistics such as means, standard deviations, medians and interquartile ranges were calculated to describe both independent and continuous variables. Variables selected for the multivariable regression model for risk estimation were based on the top stroke risk factors cited by the American Stroke

Results

During the two-year period between January 1, 2016 and December 31, 2017, a total of 260,189 in-hospital admissions were coded with ischemic stroke as a diagnosis in the NIS database. 504 (0.2%) of them were also coded during their admission for SCD. Of the 504 SCD patients, 60.3% (n = 304) were female vs. 50.3% (n = 121,688) for non-SCD patients. The Kolmogorov-Smirnov test for normality demonstrated that age lacked a normal distribution (p < 0.001) in both groups. The Shapiro-Wilk test for

Discussion

Classical risk factors for ischemic stroke onset, as described by the American Stroke Association,9 include age, history of stroke, TIA, ischemic heart disease, atrial fibrillation, diabetes mellitus, hypertension, hyperlipidemia, and smoking. These factors have previously been shown to be predictive of in hospital mortality among ischemic stroke patients as well. However, whether they are predictive of in-hospital mortality among ischemic stroke patients with concurrent SCD disease is unknown.

Summary

Sickle cell disease is a common hemoglobinopathy that significantly increases risk for ischemic stroke and its associated pathologic outcomes, including in-hospital mortality; however, the variables that are associated with mortality outcomes in these patients have not been well elucidated. Our multivariable analysis shows that while classical risk factors for ischemic stroke onset are associated with in-hospital mortality in non-sickle cell ischemic stroke patients, they are not associated

Sources of Funding

Montefiore Davidoff Department of Neurosurgery and Albert Einstein College of Medicine Office of Student Research

Declarations of Competing Interest

None

Acknowledgements

None

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  • Cited by (0)

    Grant Support

    Montefiore Davidoff Department of Neurosurgery and Albert Einstein College of Medicine Office of Student Research

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