Abstract
Background Peripheral microvascular endothelial dysfunction (PMED) has been linked to an increased risk of cardiovascular events, but there is a lack of information characterizing the predictive value of PMED for future risk of ischemic stroke (IS). Methods and Results This retrospective observational cohort study enrolled 637 patients who underwent non-invasive microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry. Reactive hyperemia peripheral arterial tonometry index ≤2 was defined as PMED. Of 280 patients with PMED, 12 (4.3%) patients developed IS, compared with only 4 (1.1%) of 357 patients without PMED during a median follow-up of 5.3 years. Patients with PMED had lower IS-free survival compared with patients without PMED (log-rank P=0.03). Cox proportional hazard ratio (HR) analyses showed that PMED predicted the incidence of IS, with a HR of 3.43, 95% CI, 1.10-10.63 (P=0.03); adjusted HR of 3.70, 95% CI, 1.18-11.59 (P=0.02) after adjusting for sex, smoking history, and atrial fibrillation; adjusted HR of 3.45, 95% CI, 1.11-10.72 (P=0.03) after adjusting for CHA(2)DS(2)-VASc score; adjusted HR of 5.70, 95% CI, 1.40-23.29 (P=0.02) after adjusting for revised Framingham Stroke Risk Score. Reactive hyperemia peripheral arterial tonometry index improved discrimination of risk for IS after adding reactive hyperemia peripheral arterial tonometry index to CHA(2)DS(2)-VASc score and revised Framingham Stroke Risk Score. Conclusions PMED was associated with a >3-fold increased risk of IS. These findings underscore the concept of the systemic nature of endothelial dysfunction, which could act as a potential marker to predict future risk of IS.