We aim to test the hypothesis that sickle cell trait (SCT) is associated with an increased risk of ischemic stroke (IS) in young adults.

Approximately 8% of African-Americans (AA) have SCT and there have been recent conflicting reports from cohort studies on the association of SCT with IS. All prior studies of SCT as a risk factor for IS focused on older stroke populations, with few data available in young adults.

Through a population-based case-control study in the Baltimore-Washington region, we identified 342 AA cases aged 15-49 years with first IS between 1992-2007 by neurologist referral and discharge surveillance. 333 controls matched for age, race, and gender were identified through random digit dialing. We used genome-wide association study (GWAS) data to impute the single nucleotide polymorphism (SNP) variant encoding SCT with a SNP imputation quality score of 0.80. For analysis, we used χ² tests and logistic regression models adjusted for age, hypertension (HTN), diabetes mellitus (DM), current smoking status, and previous myocardial infarction (MI). 

Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of classic risk factors for IS, including HTN, DM, current smoking status, and previous MI. Stroke cases had increased prevalence in these risk factors compared to controls. We did not find an association between SCT and early-onset IS in either model (unadjusted OR=0.8 [0.5-1.4]; adjusted OR=0.9 [0.5-1.7]). Given our 9.1% rate of SCT among controls and alpha=0.05, our study had 80% power to detect an OR of 1.93.

We did not find evidence of increased risk of early-onset stroke with SCT. This study further questions the association between SCT and stroke, but additional studies of young AA adults are needed to help clarify whether this association exists.