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 = 1.54; 95% CI 1.06–2.24, P < .001). The strength of this association was found to be similar (OR = 1.56; 95% CI 1.11–2.19, P < .001). A positive correlation was also found for calcium burden (OR = 1.31; 95% CI, 1.17–1.46; P < .001). Heterogeneity was moderate for calcium presence (Q = 13.16 and 9.19; I² = 62% and 42.61%, respectively); negligible for burden analysis (Q = 6.01; I² = 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. Future studies may focus on specific arterial segments and emerging calcification patterns to improve predictive accuracy