August 15, 2025Open Access

Inflammatory Markers are Associated with Ischemic Stroke among Indigenous Africans: Evidence from the SIREN Study

Key Points

Inflammation is associated with increased stroke severity and disability among indigenous Africans, pointing to a potential new area of research.
Differential protein analysis identified 23 up-regulated proteins in stroke cases, with C1qa showing the strongest association with severity.
This observational analysis utilized the SIREN cohort, comparing 90 ischemic stroke participants with 90 matched controls to identify significant biomarkers.
The findings suggest that specific inflammatory biomarkers may aid in predicting stroke outcomes, indicating the need for further validation in clinical settings.

Abstract

Background: Inflammation might predispose to worse outcomes after an ischemic stroke. This has not been characterized among indigenous Africans. Purpose: We investigated the association between inflammatory biomarkers, stroke severity, and outcomes in Africans. Methods: This is a retrospective analysis of a prospective study, including 90 participants with confirmed ischemic stroke selected from the Stroke Investigative Research & Educational Network (SIREN) cohort and 90 controls matched by age, sex, and ethnicity. Plasma concentrations of 368 protein biomarkers were analyzed and compared between cases and controls. Further, we investigated the association between these proteins and stroke severity, lesion volume, and one-month post-stroke disability and fatality. Results: Differential protein expression analysis revealed 23 up-regulated and 14 down-regulated proteins in stroke cases versus controls. Among the up-regulated proteins, agouti-related protein (AgRP) and tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) were the most significantly up-regulated, while interleukin-1 beta (IL-1β) and integrin alpha-11 (ITGA11) were the most down-regulated proteins. Logistic regression analysis identified 72 proteins that were associated with stroke severity independent of age and sex. Among these, complement C1q subcomponent subunit A (C1qa) exhibited the strongest associations. Additionally, 14 proteins including C-C motif chemokine 23 (CCL23) were found to be associated with one-month post-stroke disability. Conclusion: Stroke disability and severity were associated with inflammation in an indigenous African population. The identified biomarkers might be useful for predicting stroke outcome or serve as therapeutic target. Authors' Declaration: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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