Association between large artery stenosis, cerebral small vessel disease and risk of ischemic stroke.

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.