Abstract

Objective: Inward and outward remodeling of cerebral vessels may represent alternate pathological vascular phenotypes. Our aim was to test whether extremes of brain arterial diameters increase risk of death and vascular events. Methods: Cerebral large artery diameters were measured in 1,034 stroke-free participants from Northern Manhattan. Arteries from the Circle of Willis (8) and posterior circulation (5) were measured in regions free of stenosis, adjusted for head size, standardized, and added to create a global measure of diameters in each person. Participants were categorized into the top 5% of the diameter distribution (“outward remodelers”) and bottom 5% (“inward remodelers”), as well as an intermediate referent category (90% of population). We used logistic regression to calculate associations with risk factors and Cox models to calculate risks of outcomes after adjusting for demographic and vascular risk factors. Results: Mean follow-up was 5 ± 2 years. Inward remodelers were more likely to be men (OR 3.3, 95%CI 1.8-6.1) and less likely to be hypertensive (OR 0.5, 95%CI 0.3-0.9) or Hispanic (OR 0.3, 95%CI 0.2-0.6), while outward remodelers were more likely to be women (OR 14.6, 95%CI 3.5-60.5) and Hispanic (OR 8.7, 95%CI 1.2-65.0) compared to participants with less extreme diameters. Inward remodelers had a higher risk of death (HR 1.8, 95%CI 1.1-3.0), vascular death (HR 2.8, 95%CI 1.4-5.7), myocardial infarction (HR 2.5, 95%CI 1.0-6.4) and ischemic stroke (HR 3.4, 95%CI 1.0-10.2). Outward remodelers were not at increased risk of death or vascular events. Compared to those with less extreme diameters, risk of cardioembolic stroke was higher among inward remodelers (11.3 vs. 1.4%, HR 13.9, 95%CI 4.4-44.0) while strokes due to large or small artery disease were more frequent in outward remodelers (3.8 vs 1.8 %, HR 3.4, 95%CI 0.7-16.3). Conclusions: Individuals with the smallest brain arterial diameters are at greater risk of death, myocardial infarction, and ischemic stroke, while those with the largest brain arterial diameters were not. Cerebral arterial phenotypes might identify people at greater risk of cardiac disease and stroke, and direct targeting of primary preventive measures at likely stroke subtypes.

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