Systemic inflammatory factors combined with HR-VWI-based plaque vulnerability discriminate ischemic phenotypes and predict prognosis in patients with intracranial atherosclerosis

Abstract

Abstract Background The relationship between systemic inflammation, plaque vulnerability, and stroke phenotypes in intracranial atherosclerotic stenosis (ICAS) is unclear. This study investigated inflammatory markers’ association with high-risk plaques and their value in differentiating stroke phenotypes and predicting prognosis. Materials and methods 298 symptomatic ICAS patients were classified into acute ischemic stroke (AIS, n = 207) and delayed perfusion (DP, n = 91) groups using multimodal MRI. Plaque vulnerability was graded based on high-resolution vessel wall imaging, inflammatory indices calculated, and associations assessed using regression and mediation analysis. Results AIS patients had higher systemic inflammation and more high-risk plaques (all p < 0.05). Each Systemic Inflammation Response Index (SIRI) unit increase was associated with 32.4% higher AIS risk ( p = 0.027) and nearly threefold increased 90-day poor outcome risk ( p < 0.001). In an exploratory mediation analysis aimed at understanding how these markers jointly differentiate the two phenotypes, the association between SIRI and AIS was partially (25.9%) statistically accounted for by high-risk plaque features. A comprehensive model integrating clinical, inflammatory, and imaging markers effectively differentiated AIS from DP (AUC = 0.794). In an exploratory prognostic analysis with a small number of poor outcomes, adding SIRI improved the AUC from 0.610 to 0.959, with internal validation supporting robustness (mean cross-validated AUC: 0.919–0.939), p < 0.05. Associations were more pronounced in males. Conclusions Systemic inflammation is associated with ischemic phenotype in ICAS, and this association may be partially explained by plaque vulnerability. Combined assessment effectively differentiates stroke phenotypes and predicts prognosis, particularly in males, supporting multi-parametric models for early identification of at-risk patients. Key Points Question : Can systemic inflammatory markers combined with high-risk plaque features discriminate acute ischemic stroke from delayed perfusion and predict prognosis in patients with intracranial atherosclerotic stenosis? Findings : Systemic inflammation response index was independently associated with acute ischemic phenotypes and poor prognosis. Multi-parametric models improved phenotype discrimination (AUC = 0.794) and prognosis prediction (cross-validated AUC: 0.919–0.939). Critical relevance statement : Systemic inflammation response index is associated with acute ischemic stroke in intracranial atherosclerotic stenosis, an association partially mediated by high-risk plaque features. Combined assessment of inflammatory and imaging biomarkers improves stroke phenotyping and prognosis prediction, particularly in male patients.