Plasma S100A8/A9 Concentrations and Clinical Outcomes of Ischemic Stroke in 2 Independent Multicenter Cohorts

S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts.

Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events.

Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66-2.68) for the primary outcome and 1.62 (95% CI, 1.27-2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10-8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38-3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%-39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations.

High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.