Sickle Cell Trait May Not Contribute to Stroke Risk

Be careful out there.

Sickle Cell Trait May Not Contribute to Stroke Risk

• by Judy George, Contributing Writer, MedPage Today April 23, 2018
• This article is a collaboration between MedPage Today® and:

Action Points

• No association was found between sickle cell trait and the incidence of ischemic stroke among African Americans, in a meta-analysis of four studies with 19,464 African-American participants.
• Note that these data suggest that when a patient with sickle cell trait presents with stroke and no apparent traditional risk factors, a more thorough work-up should be done instead of assuming that the stroke is due to sickle cell trait.

Sickle cell trait may not be an independent genetic risk factor for ischemic stroke among African Americans, a new meta-analysis suggests.

In a review of four studies with more than 19,000 African-American participants, Hyacinth I. Hyacinth, MD, PhD, MPH, of Emory University School of Medicine in Atlanta, and colleagues reported no association between heterozygosity for the sickle cell mutation or sickle cell trait and incidence of ischemic stroke in JAMA Neurology.

"Sickle cell trait was not associated with a higher risk of ischemic stroke among African Americans," Hyacinth told MedPage Today. "This negative study and its findings are important as we attempt to develop more targeted approaches for stroke prevention."

"Significant stroke disparity exists between African Americans and non-Hispanic whites," he said. "Because this disparity is not explained by traditional risk factors such as access to healthcare, identifying biological factors that account for the differences is an important strategy for stroke prevention."

This negative result tells neurologists to dig deeper, Hyacinth added: "When a patient with sickle cell trait presents with stroke and no apparent traditional risk factors, a more thorough work-up should be done, instead of just pinning the stroke on the fact that the patient has sickle cell trait."

Case reports have suggested that sickle cell trait, a genetic variant that is present almost exclusively in African Americans, and ischemic stroke are linked. A prospective, population-based study also reported an association between sickle cell trait and incident stroke in African Americans.

The meta-analysis included four prospective studies that evaluated cardiovascular disease risk factors in U.S. populations: the Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis (MESA), Reasons for Geographic and Racial Differences in Stroke (REGARDS), and Women's Health Initiative.

The four studies examined 19,464 African Americans with an average age of 60; 27% were men and 73% women. In total, 1,520 people had sickle cell trait and 620 people had incident ischemic stroke. Sickle cell trait prevalence ranged from 7.7% to 9% and averaged 7.8%, consistent with estimates in the African American population.

In each cohort, the distribution of risk factors, number of strokes, and age at ischemic stroke event was similar between patients with and without sickle cell trait.

In the meta-analysis, the crude incident rate for ischemic stroke did not vary between individuals who had sickle cell trait (2.9 per 1,000 person years) and those who did not (3.2 per 1,000 person-years). After adjusting for stroke risk factors, the hazard ratio of incident ischemic stroke independently associated with sickle cell trait was 0.80 (95% CI 0.47-1.35, P=0.82). Meta-analysis results were similar to those of individual cohorts.

"We know ischemic stroke is increased in individuals with sickle cell disease, but prior studies looking for an association with sickle cell trait have been mixed," observed Sarah Lee, MD, of the Stanford University School of Medicine, who was not involved in the study.

"This large meta-analysis confirms our suspicion that sickle cell trait does not seem to confer an increased risk of stroke, and will be helpful when counseling patients and considering stroke prevention in this population," Lee told MedPage Today.

Hyacinth and co-authors noted that previous evidence of an association between sickle cell trait and ischemic stroke included the longitudinal Atherosclerosis Risk in Communities (ARIC) study of 3,497 African Americans that reported a 1.4-fold increased risk of ischemic stroke in sickle cell trait carriers.

Several factors could explain why those results vary from this meta-analysis. In the meta-analysis, the number of people with sickle cell trait in age groups with greater risk of stroke in each cohort was relatively small, so differences may have been caused by chance. It's also possible different covariates were used.

In the meta-analysis, researchers adjusted for left ventricular hypertrophy; the ARIC study did not make that adjustment. But adjusting for left ventricular hypertrophy did not change the direction of estimate effects, the authors noted.

One limitation of the meta-analysis was possible misclassification, as about 48% of the sample were not genotyped directly. However, effect estimates and lack of association were similar in studies with and without direct genotyping. The researchers also could not test the association of sickle cell trait with ischemic stroke subtypes, so it remains possible that a link exists between sickle cell trait and one or more stroke subtype.

This work was supported in part by the National Cancer Institute and the Intramural Research Program of the NIH.

The researchers reported no conflicts of interest.

• Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 04.24.2018

• Primary Source

  JAMA Neurology

  Source Reference: Hyacinth H, et al "Association of sickle cell trait with ischemic stroke among African Americans: A meta-analysis" JAMA Neurology 2018; DOI:10.1001/jamaneurol.2018.0571.