NLRP3 Inflammasome and IL-1–Mediated Inflammation in Human Carotid Atherosclerosis: A Systematic Review of Endarterectomy-Based Evidence

Background: Carotid atherosclerosis and plaque instability are major drivers of ischemic stroke. The NLRP3 inflammasome and interleukin-1 (IL-1) pathway are recognized as key upstream regulators of atherogenesis. This systematic review aims to synthesize the available evidence regarding the impact of NLRP3 and IL-1-mediated inflammation on plaque vulnerability and clinical outcomes in patients undergoing carotid endarterectomy (CEA). Materials and Methods: A systematic search was performed relying on MEDLINE, Scopus, and Web of Science for studies assessing NLRP3 inflammasome and IL-1-mediated biomarkers in adult patients undergoing CEA. Data extraction and risk-of-bias evaluation were independently performed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool. Due to substantial methodological heterogeneity, a narrative synthesis was conducted. Results: Sixteen studies involving 1677 participants were included. Evidence demonstrates that NLRP3 inflammasome components (NLRP3, ASC, Caspase-1) and IL-1 family cytokines (IL-1β, IL-18) are consistently elevated in unstable plaques and in symptomatic patients compared to asymptomatic counterparts. These markers were associated with histological features of instability, such as intraplaque haemorrhage, large lipid cores and extensive macrophage infiltration. While some data suggest a link between these biomarkers and Major Adverse Cardiovascular Events (MACE), most studies were limited by a lack of adjusted multivariable modelling and an overall unclear risk of bias. Conclusions: NLRP3/IL-1/-mediated inflammation is a promising biomarker axis for carotid plaque vulnerability and symptomatic disease. However, small, heterogeneous cohorts and limited adjusted analyses highlight the need for larger, well-designed studies to refine risk stratification and guide targeted anti-inflammatory strategies in carotid atherosclerosis.