A Systematic Review of Dynamic Cerebral and Peripheral Endothelial Function in Lacunar Stroke Versus Controls

Abstract

The etiology of cerebral small vessel disease is unknown. An association with endothelial dysfunction has been suggested. We systematically assessed all relevant studies of dynamic endothelial function in patients with lacunar stroke as a marker of small vessel disease. We searched for studies of cerebral or peripheral vascular reactivity in patients with lacunar or cortical (ie, large artery atheromatous) ischemic stroke or nonstroke control subjects. We calculated standardized mean difference (SMD) in vascular reactivity+/-95% CIs between small vessel disease and control groups. Sixteen publications (974 patients) were included. In lacunar stroke, cerebrovascular reactivity (n=534) was reduced compared with age-matched normal (SMD -0.94, 95% CI -1.17 to -0.70), but not age+risk factor-matched control subjects (SMD 0.08, 95% CI -0.36 to 0.53) or cortical strokes (SMD -0.29, 95% CI -0.69 to 0.11); forearm flow-mediated dilatation (n=401) was reduced compared with age-matched normal control subjects (SMD -1.04, 95% CI -1.33 to -0.75) and age+risk factor-matched control subjects (SMD -0.94, 95% CI -1.26 to -0.61), but not cortical strokes (SMD -0.23, 95% CI -0.55 to 0.08). Endothelial dysfunction is present in patients with lacunar stroke but may simply reflect exposure to vascular risk factors and having a stroke, because a similar degree of dysfunction is found in cortical (large artery atheromatous) stroke. Current data do not confirm that endothelial dysfunction is specific to small vessel stroke. Future studies should include control subjects with nonlacunar stroke.