Is Sickle Cell Trait a Risk Factor for Stroke and Cerebral Small Vessel Disease? Public Deposited

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  • March 19, 2019
  • Caughey, Melissa
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • We have recently shown an association between sickle cell trait (SCT) and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. The etiology of stroke in this population is unclear, however. Though not considered a hematological disorder, the SCT phenotype is nonetheless associated with hypercoagulability, vasculopathy, and possibly hypoperfusion. To further understand the cerebrovascular pathophysiology, we examined a subset of African Americans in the ARIC study (N=844, mean age=62, female=64%) who were prospectively imaged by cerebral MRI in 1993-1995, and 470 (56%) who returned for a follow up MRI in 2004-2006. White matter lesions (WML) and subclinical brain infarctions (SBI) in participants with no prior history of stroke were detected by cerebral MRI. Associations between SCT and WML prevalence and severity were analyzed using ordinal logistic and linear regression. Similarly, associations between SCT and the prevalence and progression of SBI were analyzed using logistic regression. Models were adjusted for age, sex, cerebrovascular risk factors, and 10 principal components of ancestry. SCT was identified in 56 (6.6%) participants at the first MRI. Individuals with SCT had more prevalent (86% vs. 79%), and more severe (mean score 1.5 vs. 1.3) WML than individuals without SCT. SCT was also associated with a 20% increased odds of WML prevalence (POR 1.2, 95% CI: 0.7 - 2.0), and an adjusted mean severity score that was 0.2 (-0.1 - 0.5) points higher; however neither of these estimates was statistically significant. Likewise, SCT was not associated with prevalent SBI (POR = 0.7; 95% CI: 0.3 - 1.8), or incidence of new infarctions by the follow up exam (OR = 1.4; 95% CI: 0.6 - 3.1). In conclusion, we observed no statistically significant associations between SCT and cerebral small vessel disease. There was a trend for greater WML prevalence and severity among those with SCT, as well as a higher 11-year incidence of SBI; however, the estimates were imprecise and inconclusive.
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  • In Copyright
  • Heiss, Gerardo
  • Gottesman, Rebecca
  • Loehr, Laura
  • Key, Nigel
  • North, Kari
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
Place of publication
  • Chapel Hill, NC
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