Age-related risk of vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis

Abstract: BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) carries major morbidity; delayed cerebral ischemia (DCI) is a key driver. Vasospasm is implicated, but the effect of age is uncertain. We systematically reviewed and meta-analyzed the association between age and radiographic vasospasm (RVS), symptomatic vasospasm (SVS), and DCI. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched through May 2024. We included adult aSAH studies reporting multivariable analyses of continuous age versus RVS, SVS, or DCI. Random-effects odds ratios (ORs) per year were pooled; heterogeneity ( I 2 ) and sensitivity (leave-one-out, Baujat, graphical display of study heterogeneity) were assessed. Risk of bias used ROBINS-I; certainty used GRADE. RESULTS: Of 2,108 records, 23 studies (8,843 patients; 9,934 data points) met criteria. Younger age was associated with higher RVS risk (OR per year 0.97; 95% confidence interval CI: 0.95–0.99; I 2 = 74%), persisting after sensitivity analyses and outlier removal (OR 0.97; 95% CI: 0.95–0.98; I 2 = 0%). Age was not significantly associated with SVS (OR 0.99; 95% CI: 0.98–1.00; I 2 = 79%) or DCI (OR: 1.04; 95% CI: 0.92–1.16; I 2 = 90%), although SVS showed a nonsignificant trend toward greater risk in younger patients. DCI heterogeneity was largely driven by two outlier studies. Overall risk of bias was moderate; certainty was moderate for vasospasm outcomes and low for DCI. CONCLUSIONS: Younger age independently predicts RVS but not DCI after aSAH. These findings underscore that DCI reflects mechanisms beyond large-vessel spasm and support age-tailored risk stratification and investigation of microvascular and inflammatory pathways.