Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis

Abstract

Background and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. Methods: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. Results: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89–1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58–0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07–1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02–1.90). Conclusions: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Procedural Outcome Following Stent-Assisted Coiling for Wide-Necked Aneurysms Using Three Different Stent Models: A Single-Center Experience

“…Interestingly, even in our cohort that only consisted of wide-necked aneurysms, these findings were stable and may be considered a priori as negative prognostic predictors for complete occlusion in patients treated with SAC for wide-necked aneurysms. Furthermore, female sex was independently associated with aneurysm obliteration, which is most likely biased by the fact that aneurysm cohorts are likely to include higher numbers of women than men because female sex is a common risk factor for developing intracranial aneurysms and rupture [ 24 , 25 , 26 ].…”

Screening and Management for Intracranial Aneurysms in Japanese Patients With ADPKD

“…This rate was potentially higher than the previous report. 9 This finding in this study suggests that magnetic resonance angiography should be repeated for all patients with ADPKD without ICA at regular intervals.…”

“…In addition, it is recently reported that female was associated with ICA rupture though the pathophysiology remains unclear. 9 Although no ICA had not been ruptured in all female ADPKD patients during followup in our study probably because the study size was small and regular follow-up of magnetic resonance angiography prevented and detected ICA at high risk of rupture, physicians should take more care over female patients.…”

DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males

“…Sex dichotomous effects and age are implicated in the risk factors of IA and many gene methylation rates (Vlak et al, 2011 ; Unnikrishnan et al, 2019 ; Li and Liu, 2021 ). The prevalence of IA and the risk of aneurysmal rupture in females are higher than those in males (Zuurbier et al, 2022 ). DNA methylation also shows strong sex-specific differences when individuals are exposed to harsh environments (Curtis et al, 2020 ).…”