Sex-specific association between anatomical variants of the circle of Willis and intracranial aneurysms in individuals with a familial predisposition

BACKGROUND AND PURPOSE: First-degree relatives of aneurysmal subarachnoid hemorrhage patients face elevated risks for intracranial aneurysm development and aneurysmal subarachnoid hemorrhage, which both occur more often in women. Anatomical variants of the circle of Willis affect its hemodynamics and are associated with unruptured intracranial aneurysms. 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 anatomical circle of Willis 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-TOF screening, were compared. Circle of Willis arterial diameters were measured to identify anatomical variants, categorized into six 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 1,291 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 circle of Willis.

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

ABBREVIATIONS: ACA = anterior cerebral artery; Acom = anterior communicating artery; ADPKD = autosomal dominant polycystic kidney disease; aSAH = aneurysmal subarachnoid hemorrhage; CoW = circle of Willis; PCA = posterior cerebral artery; Pcom = posterior communicating artery; UIA = unruptured intracranial aneurysm; UMCU = University Medical Center Utrecht.