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

Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.