In African Americans, sickle cell trait (SCT) is not associated with ischemic stroke and should not be relied upon as a sole predictor of stroke in these patients, according to a study published in JAMA Neurology.

Data were pooled from 4 prospective population-based studies that included 19,464 African Americans. A total of 1520 study participants had SCT and 620 had incident ischemic stroke. Studies included in the meta-analysis included the Jackson Heart Study (JHS), MultiEthnic Study of Atherosclerosis (MESA), Reasons for Geographic and Racial Differences in Stroke (REGARDS), and Women’s Health Initiative (WHI).

The presence of the minor allele of the rs334 single-nucleotide polymorphism, which encodes for the HBB p.Glu7Val mutation, defined SCT in this analysis. In addition, the first adjudicated ischemic stroke event that occurred following completion of study enrollment and baseline examination defined incident ischemic stroke.

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In the crude analysis, there was no difference between patients with vs without SCT in terms of ischemic stroke incidence rate (2.9 per 1000 person-years [95% CI, 2.2-4.0 per 1000 person years] vs 3.2 per 1000 person-years [95% CI, 2.7-3.8 per 1000 person-years], respectively).

In addition, the adjusted analysis showed no difference between SCT and non-SCT patients in terms of ischemic stroke incidence rate in all four studies (hazard ratio, 0.80 [95% CI, 0.47-1.35; P =.82).

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Considering almost 50% of the overall cohort was not genotyped for SCT, there is a possibility that misclassification of SCT status occurred in the included studies.

Investigators of this meta-analysis suggest future studies that include patients with “carefully subtyped ischemic stroke events are needed to further elucidate the possible association of SCT with incident ischemic stroke overall and by specific ischemic stroke subtypes.”


Hyacinth HI, Carty CL, Samantha R. Seals, P, et al. Association of sickle cell trait with ischemic stroke among African Americans: A meta-analysis [published online April 23, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2018.0571