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

BACKGROUND: Intracranial atherosclerosis accounts for about 8% of all strokes in Western societies but the influence of arterial calcification on plaque instability is a topic on ongoing debate.

PURPOSE: 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: Adhering to PRISMA guidelines, studies from PubMed and Embase were analyzed up to May 2024.

STUDY SELECTION: Adult populations undergoing CT/CTA scans for symptomatic and asymptomatic atherosclerosis among intracranial vessels.

DATA ANALYSIS: Statistical analyses were performed to identify the impact of calcium presence and relative burden on stroke incidence or recurrence. Risk of bias was evaluated with QUADAS-2 criteria while GRADE system was used to assess quality of evidence.

DATA SYNTHESIS: The study synthesized data from 8 longitudinal studies, creating two different models: Calcium presence (heterogeneity: Q 9.19; I² 42.61%) and calcium burden (heterogeneity: Q 6.01; I² 0.01%). As for calcium presence and stroke events, 6839 patients were considered, and two statistical models were made. Our analysis established a significant association between the presence of calcium and stroke events. [OR= 1.54, 95% CI 1.06, 2.24, p=0.001]. A subsequent effect size analysis showed a similar correlation’s strength [OR = 1.56, 95% CI 1.11, 2.19, p = 0.001]. As for calcium burden and stroke events, 4885 patients were considered with effect size analysis establishing a positive correlation [OR = 1.31, 95% CI, 1.17, 1.46, p =< 0.001). A decrease in correlation strength was found between calcium presence [OR = 1.56] and burden [OR = 1.31] with stroke events.

LIMITATIONS: Despite strict exclusion criteria, heterogeneity across studies and between different statistical models of the present study persisted. Valuable data loss among excluded studies could have affected the findings of this meta-analysis. Unified calcium scoring pattern and individual arterial segment analysis was not widely adopted by included literature.

CONCLUSIONS: Our meta-analysis showed a weak, yet present association between presence and burden of calcification among intracranial arterial vessels and clinical or silent stroke events. Considering the high prevalence of intracranial calcification in the general population, widespread intracranial calcium assessment for stroke prediction has currently poor evidence. Investigation on specific intracranial vessels or exploration of newer calcium patterns could be essential to enhance the predictive accuracy of calcification in stroke incidence or recurrence.

ABBREVIATIONS: IAC = Intracranial Arterial Calcification; HU = Hounsfield Unit; RE = Random Effect.