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

Stroke. 2022 Feb;53(2):362-369. doi: 10.1161/STROKEAHA.121.035187. Epub 2022 Jan 5.

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.

Keywords: intracranial aneurysm; prevalence; risk factor; sex; subarachnoid hemorrhage.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aneurysm, Ruptured / epidemiology*
  • Cohort Studies
  • Female
  • Humans
  • Intracranial Aneurysm / complications*
  • Intracranial Aneurysm / epidemiology*
  • Male
  • Middle Aged
  • Prevalence
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Smoking / epidemiology
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / epidemiology