Risk factors for saccular unruptured intracranial aneurysms: a systematic review and meta-analysis

INTRODUCTION: Intracranial aneurysms are often unruptured and two-thirds of patients with unruptured intracranial aneurysms (UIAs) are women. Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage (aSAH). While risk factors for aSAH have been extensively studied, those for UIA remain less well understood. We performed a systematic review and meta-analysis to identify risk factors for the presence of saccular UIAs and assess potential sex differences. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies on risk factors for UIA up to March 2024. Assessed risk factors included smoking, hypertension, alcohol use, diabetes, hypercholesterolaemia, physical activity, and body mass index. We performed random-effects meta-analyses to calculate pooled odds ratios (ORs) and 95% CIs for each risk factor. RESULTS: We identified 21 studies reporting on overall 347 907 participants and 8698 UIA cases. Hypertension (OR 1.72, 95% CI, 1.42-2.09) and smoking (OR 1.47, 95% CI, 1.11-1.95) were associated with the presence of UIAs. No statistically significant associations were found for the other assessed risk factors. Among 18 studies that included both sexes, only one provided sex-stratified results, preventing us from assessing potential sex differences. DISCUSSION: Future research should consistently report sex-stratified results to enable investigation of potential sex differences in UIA risk factors and further explore female-specific risk factors that may contribute to the high female preponderance in UIA. CONCLUSION: Hypertension and smoking are associated with an increased risk of UIAs. The lack of sex-stratified data limits conclusions about sex-specific risk profiles.