Cracking the Code of Calcification: How Presence and Burden among Intracranial Arteries Influence Stroke Incidence and Recurrence

BACKGROUND: Intracranial atherosclerosis accounts for approximately 8% of all strokes in Western societies but the influence of arterial calcification on plaque instability is a topic of ongoing debate. PURPOSE: Our purpose is to explore the association between the presence and burden of calcium in atherosclerotic plaques among intracranial arteries with the risk of clinical or silent stroke events through a systematic review and meta-analysis. DATA SOURCES: Studies from PubMed and Embase investigating intracranial vessel calcification and stroke events were reviewed from inception through May 2024, adhering to PRISMA guidelines. STUDY SELECTION: Eight longitudinal studies involving 7297 adult patients undergoing CT or CTA scans for symptomatic or asymptomatic intracranial atherosclerosis were included. DATA ANALYSIS: Pooled odds ratios were calculated to assess the relationship between stroke events and either the presence or burden of intracranial arterial calcification. Quality assessment was conducted using QUADAS-2; overall evidence was established using GRADE system. Meta-analysis was performed using random-effects models. DATA SYNTHESIS: After adjusting for confounding factors, the presence of intracranial arterial calcification was significantly associated with stroke incidence or recurrence (OR ¼ 1.54; 95% CI 1.06–2.24, P, .001). The strength of this association was found to be similar (OR ¼ 1.56; 95% CI 1.11–2.19, P, .001). A positive correlation was also found for calcium burden (OR ¼ 1.31; 95% CI, 1.17–1.46; P, .001). Heterogeneity was moderate for calcium presence (Q ¼ 13.16 and 9.19; I² ¼ 62% and 42.61%, respectively); negligible for burden analysis (Q ¼ 6.01; I² ¼ 0.01%). LIMITATIONS: Despite strict inclusion criteria, heterogeneity and variability in calcium scoring methods across studies were observed. The lack of segment-specific analysis may have limited clinical interpretation. CONCLUSIONS: This meta-analysis demonstrates a weak yet present association between intracranial arterial calcification and stroke events. However, given the high prevalence of calcification in the general population, its role for stroke prediction has limited evidence.