Isabella Canavero, MD

Zuurbier CCM, Molenberg R, Mensing LA, Wermer MJH, Juvela S, Lindgren AE, Jääskeläinen JE, Koivisto T, Yamazaki T, Uyttenboogaart M, et al. Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis. Stroke. 2022.

A higher prevalence of both intracranial aneurysms and aneurysmal subarachnoid hemorrhage (aSAH) in women than in men has been reported by many studies. However, female sex has not been identified as an independent risk factor in rupture rate of intracranial aneurysms according to the PHASES score, which is a validated scoring system that takes into account both patient- and aneurysm-related features, including geographic location, hypertension, age, history of aSAH, aneurysm size and location.

By hypothesizing a different prevalence of patient- or aneurysm-related risk factors for rupture (including the PHASES score, smoking, and a positive family history for aSAH) among sexes, Zuurbier and colleagues performed a pooled analysis of individual patient data from nine prospective cohort studies, examining about 10000 patients, to assess if sex is an independent risk factor for rupture.

Of note, the selected studies had low to moderate risk of bias, and patient features were almost completely (98 to 100% of cases) detailed.

Interestingly, the analysis pointed out that although women still exhibit a higher risk of aneurysmal rupture, that seems not explained by differences in the prespecified patient- and aneurysm-related risk factors.

If the strength of the study is fostered by a large sample and many clinical variables, some incomplete information could have affected the interpretation of results: For example, data describing the approach given to modifiable risk factors such as smoking during follow-up were not available, and this could have at least partially impacted sex differences in aneurysmal rupture rate.

The authors correctly suggested the likely existence of additional factors contributing to the female increased risk, which remain to be detected. Potential candidates could be represented by aneurysm morphology, sex-related hormonal and reproductive factors, genetic and environmental factors and life habits. Preliminary evidence offered by this study suggests that considering a more aggressive treatment approach for intracranial aneurysm in women might be justified.