Contribution of the NLRP3 rs10754558 (C>G) variant and inflammatory and hemostatic biomarkers to acute ischemic stroke outcome

Abstract

The interaction between inflammation, hemostatic pathways, and genetic susceptibility in acute ischemic stroke (AIS), particularly involving the NLRP3 inflammasome, remains incompletely understood. We investigated whether the NLRP3 rs10754558 (C>G) variant and inflammatory and hemostatic biomarkers are associated with AIS outcomes. The prospective study included 134 AIS patients stratified using a composite clinical outcome index (PC outcome) integrating baseline National Institute of Health Stroke Scale (NIHSS), 3-month modified Rankin Scale, and 3-month mortality. An Inflammation Index was derived from C-reactive protein, white blood cell count, and inverse albumin levels. NLRP3 rs10754558 (C>G) genotypes and inflammatory and hemostatic biomarkers were assessed. Patients with worse outcomes were older, had lower body mass index (BMI), and showed higher systemic inflammation and von Willebrand factor levels. Factor VIII activity, NLRP3 GG genotype in a recessive genetic model (GG vs. GC + CC), Protein C, and sex emerged as significant predictors, explaining 24.1% of the variance in the outcome variable. Baseline NIHSS and the Inflammation Index predicted 3-month mortality, while lower BMI and higher inflammation predicted worse clinical outcomes. The effects of NLRP3 genotype, Factor VIII, and Protein C on clinical outcome were mediated by inflammation. Systemic inflammation was independently associated with mortality and unfavorable clinical outcomes after AIS and may partially explain a potential link between hemostatic alterations, the NLRP3 rs10754558 variant, and prognosis. These findings may suggest an inflammation–coagulation–genetic interaction in AIS and that inflammation may be a useful target for prognostic stratification and future therapeutic intervention.