ABSTRACT NUMBER: ESOC2026A294 LARGE ARTERY PHENOTYPES, CEREBROVASCULAR FUNCTION, AND PROGRESSION OF CEREBRAL SMALL VESSEL DISEASE

Abstract Background and aims Cranial artery stenosis and dilatation are distinct large artery phenotypes that often coexist with cerebral small vessel disease (cSVD), yet their downstream microvascular functional correlates remain poorly characterized. Methods In the prospective Mild Stroke Study, we recruited patients with lacunar or mild non-lacunar stroke. Large artery stenosis (LAS), basilar artery dolichoectasia (BADE), and intracranial arterial diameters were assessed. Multimodal MRI quantified cerebrovascular reactivity (CVR), blood-brain barrier (BBB) permeability, plasma volume fraction, and intracranial pulsatility. cSVD markers were assessed at baseline and 1 year. Associations between large artery phenotypes and vascular function were examined with multivariable regression adjusted for risk factors, and mediation analyses tested whether vascular dysfunction linked large artery pathology to cSVD progression. Results A total of 224 participants (66.0 ± 11.2 years; 66.5% men) were included. BADE (n=36, 16.1%) was independently associated with lower CVR in normal-appearing white matter (NAWM; β −0.01, 95% CI −0.016 to −0.004, P=0.003). Larger mean intracranial arterial diameter was associated with lower CVR, but not with pulsatility. Arterial diameter showed a U-shaped association with BBB permeability. LAS (n=46, 20.5%) was was associated with higher plasma volume in WMH. CVR in NAWM partially mediated the association between BADE and both baseline cSVD burden and 1-year progression. Conclusions Large artery dilatation may serve as a macroscopic signal of small-vessel dysfunction, being associated with lower CVR and altered BBB permeability. Reduced CVR in NAWM partially mediated the impact of dolichoectasia on cSVD progression and may represent a potential therapeutic target to slow disease progression. Conflict of interest Nothing to disclose