EXPRESS: Inflammatory cytokines, high sensitivity CRP, and risk of 1-year vascular events, death and poor functional outcome after stroke and TIA
Background Inflammation driven by pro-inflammatory cytokines is a new therapeutic target in coronary disease. Few data exist on the association of key upstream cytokines and post-stroke recurrence. In a prospective cohort study, we investigated the association between pivotal cytokines, CRP and 1-year outcomes. Methods BIO-STROKETIA is a multi-centre prospective cohort study of non-severe ischemic stroke (mRSâ¤3) and TIA. Controls were patients with transient symptoms attending TIA clinics with non-ischemic final diagnosis. Exclusion criteria were severe stroke, infection and other pro-inflammatory disease. High-sensitivity serum C-reactive protein (CRP) and cytokines (interleukin [IL] 6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ], tumor-necrosis factor-α [TNF-α]) were measured. The primary outcome was 1-year recurrent stroke/coronary events (fatal and non-fatal). Results 680 patients (439 stroke, 241 TIA) and 68 controls were included. IL-6, IL-1β, IL-8, IFN-γ, TNF-α, and CRP were higher in stroke/TIA cases (pâ¤0.01 for all). On multivariable Cox regression, IL-6, IL-8, and CRP independently predicted 1-year recurrent vascular events (adjusted HRs [aHR] per-quartile increase IL-6 1.31,CI 1.02-1.68, p=0.03; IL-8 1.47, CI 1.15-1.89, p=0.002; CRP 1.28 CI, 1.01-1.62, p=0.04). IL-6 (aHR 1.98, CI 1.26-3.14, p=0.003) and CRP (aHR 1.81, CI 1.20-2.74, p=0.005) independently predicted 1-year fatality. IL-6 and CRP (adjusted OR per-unit increase 1.02, CI 1.01-1.04) predicted poor functional outcome, with a trend for IL-1ï¢ (p=0.054). Conclusion Baseline inflammatory cytokines independently predicted late recurrence, supporting a rationale for randomised trials of anti-inflammatory agents for prevention after stroke and suggesting that targeted therapy to high-risk patients with high baseline inflammation may be beneficial.