Systemic Inflammatory Markers and Intracranial Atherosclerosis: Road to Nowhere? A Meta-analysis

Background and purpose: Intracranial atherosclerosis (ICAS) is a major cause of stroke worldwide, highly prevalent in Asian populations. While systemic inflammation plays a well-established role in the onset and progression of extracranial atherosclerosis, its relevance to ICAS remains poorly defined. This meta-analysis aimed to evaluate the association between systemic inflammatory markers and ICAS presence and progression. Methods: The meta-analysis was performed with a comprehensive literature search that identified 292 studies, of which 12 met inclusion criteria, encompassing 19674 patients. After stratification by three biomarkers (hs-CRP, CRP, NLR), the analysis assessed the association with ICAS presence using random-effects models to estimate effect sizes. ICAS progression analysis could not be performed due to insufficient data. Results: A negligible effect size magnitude was found between ICAS presence and both hs-CRP (Cliff's Delta = 0.090, 95% CI: 0.043-0.137) and NLR (Cliff's Delta = 0.151, 95% CI 0.104-0.198). Uncertainty about effect size existence or direction was found for CRP (Cohen's d = 0.145, 95% CI: -0.072-0.361). Heterogeneity was low for NLR (I² = 39.7%), but high for hs-CRP and CRP (I² = 98.5% and 71.9%, respectively). Conclusions: Increased inflammatory biomarkers do not lead to increased ICAS presence, raising concern about the actual role of systemic inflammation in ICAS pathophysiology. Despite substantial heterogeneity, the direction and magnitude of effect sizes were consistent across biomarkers. Future multicenter, prospective studies are further needed to define the role of inflammation in ICAS progression.