Inflammatory cytokines and ischemic stroke risk
The REGARDS cohort
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Abstract
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.
Glossary
- CI=
- confidence interval;
- CRP=
- C-reactive protein;
- CV=
- coefficient of variation;
- CVD=
- cardiovascular disease;
- HR=
- hazard ratio;
- IL=
- interleukin;
- REGARDS=
- Reasons for Geographic and Racial Differences in Stroke
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* Deceased.
CME Course: NPub.org/cmelist
- Received May 29, 2018.
- Accepted in final form January 17, 2019.
- © 2019 American Academy of Neurology
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