Sex-Specific Association between Anatomic Variants of the Circle of Willis and Intracranial Aneurysms in Individuals with a Familial Predisposition.

Abstract

Background and purpose: First-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH) face elevated risks for intracranial aneurysm development and aSAH, which both occur more often in women. Anatomic variants of the circle of Willis (CoW) affect its hemodynamics and are associated with unruptured intracranial aneurysms (UIAs). It is unknown if these findings apply to patients with a familial predisposition for these conditions and if they are sex-specific. We, therefore, assessed if anatomic CoW variants are associated with intracranial aneurysms identified at screening in individuals with a familial predisposition and if these associations are sex-specific.

Materials and methods: Individuals with and without intracranial aneurysms, identified at MRA time-of-flight screening, were compared. CoW arterial diameters were measured to identify anatomic variants and categorized into 6 types for both the anterior and posterior parts. Logistic regression was used for comparison, adjusted for age, hypertension, and the cohorts the individuals were part of, and stratified for sex-specific subgroups.

Results: Of all 1291 included individuals, 94 (7.3%) had aneurysms. A normal anterior variant was less common among individuals with aneurysms (OR 0.59, 95% CI: 0.37-0.93). This effect was only observed in women (OR 0.45, 95% CI: 0.25-0.80) and not in men (OR 1.39, 95% CI: 0.57-3.35). The variant with anterior communicating artery hypoplasia or absence was more common in individuals with aneurysms (OR 1.61, 95% CI: 1.03-2.54). This effect was observed in both women (OR 1.62, 95% CI: 0.95-2.75) and men (OR 1.37, 95% CI: 0.55-3.41). No differences were found for variants of the posterior part of the CoW.

Conclusions: Women with intracranial aneurysms identified at screening less frequently had a normal anterior part of the CoW compared with those without aneurysms. Additionally, individuals with aneurysms more often had anterior communicating artery hypoplasia or absence, which association was not sex-specific. These anatomic variations may enhance the effectiveness of screening for intracranial aneurysms.