Inflammatory cytokines and ischemic stroke risk: The REGARDS cohort
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Published on: March 1, 2011
Nancy Swords Jenny1, Peter W Callas1, Suzanne E Judd1
1From the Departments of Pathology and Laboratory Medicine (N.S.J., N.A.Z., M.C.) and Medicine (N.A.Z., M.C.), University of Vermont Larner College of Medicine, Burlington; Department of Biometry (P.W.C.), University of Vermont, Burlington; Department of Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Epidemiology and Biostatistics (L.A.M.), Dornsife School of Public Health, Drexel University, Philadelphia, PA; and Department of Neurology and Rehabilitation Medicine (B.K.), University of Cincinnati College of Medicine, OH.
Insights
Interleukin-6 (IL-6) is linked to higher ischemic stroke risk and explains racial disparities in stroke incidence among Black individuals, mediated by inflammatory risk factors.
Area of Science:
- Cardiovascular Science
- Immunology
- Epidemiology
Background:
- Stroke incidence disproportionately affects the Black population.
- Inflammatory markers, such as interleukins, are implicated in cardiovascular disease pathogenesis.
- Understanding the role of specific cytokines in racial disparities is crucial for targeted interventions.
Purpose of the Study:
- To investigate the association between circulating interleukin-6 (IL-6), IL-8, and IL-10 levels and incident ischemic stroke risk.
- To determine if these cytokines mediate the observed racial disparity in stroke incidence between Black and White individuals.
Main Methods:
- A case-cohort study design was employed within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
- Baseline IL-6, IL-8, and IL-10 concentrations were measured in a cohort of 30,237 Black and White adults (≥45 years).
- Incident stroke cases (n=557) and a subcohort (n=951) were analyzed over a 5.4-year follow-up period.
Main Results:
- Elevated IL-6 levels were significantly associated with incident stroke risk (HR for highest vs. lowest quartile: 2.4) and remained significant after adjusting for risk factors (HR: 2.0).
- IL-8 and IL-10 showed weaker associations with stroke risk.
- IL-6 mediated the racial disparity in stroke risk, primarily through its association with inflammatory risk factors.
Conclusions:
- Interleukin-6 is a significant independent predictor of incident ischemic stroke in a biracial population.
- IL-6 plays a mediating role in the racial disparity of stroke incidence, linked to inflammatory pathways of risk factors.
- Further research into the clinical utility of IL-6 for stroke risk assessment is warranted.
Objective:
We studied circulating interleukin (IL)-6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population.
Methods:
The Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case-cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample.
Results:
IL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; p < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2-3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black-white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors.
Conclusions:
In this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful.
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