Interaction between vertebral artery hypoplasia and circle of Willis variants in posterior circulation stroke and TIA

Background: The clinical relevance of posterior Circle of Willis (CoW) variants remains controversial, particularly in the presence of vertebral artery hypoplasia (VAH). We aimed to evaluate whether posterior CoW configuration modifies the risk of posterior circulation stroke (PCS) or transient ischemic attack (TIA) depending on vertebral artery anatomy. Methods: In this retrospective case-control study, 1,339 participants were included, comprising 269 patients with PCS/TIA and 1,070 asymptomatic controls. All subjects underwent magnetic resonance or computed tomography angiography; extracranial vertebral arteries were additionally assessed by duplex ultrasonography. VAH was defined as a vertebral artery (VA) diameter < 2.5 mm along its entire course. Posterior CoW configuration was categorized as adult-type with both posterior communicating arteries (PComAs) present, adult-type with one or both PComAs absent, or fetal-type Circle of Willis. Multivariable logistic regression, stratified and interaction analyses were performed adjusting for age, sex, and classical vascular risk factors. Results: In the overall cohort, posterior CoW configuration was not independently associated with PCS/TIA after multivariable adjustment. Stratified analyses revealed marked effect modification by VAH. Among participants with VAH, adult-type configuration with both PComAs absent was associated with higher odds of PCS/TIA (OR 2.2, 95% CI 1.3-3.6), whereas fetal-type CoW was associated with a significantly lower risk (OR 0.35, 95% CI 0.17-0.70). In contrast, among participants without VAH, fetal-type CoW was associated with increased PCS/TIA risk (OR 1.76, 95% CI 1.04-2.9). Interaction analyses confirmed significant interactions between VAH and both absent PComAs and fetal-type CoW configurations. Conclusion: The clinical impact of posterior Circle of Willis variants is strongly context dependent. Fetal-type configuration appears protective in the presence of vertebral artery hypoplasia but may increase ischemic vulnerability in individuals with normal vertebral arteries, highlighting the importance of integrating vertebral artery anatomy when interpreting posterior Circle of Willis variants.