Cerebral Small Vessel Disease and Risk of Death, Ischemic Stroke, and Cardiac Complications in Patients With Atherosclerotic Disease

Background and Purpose— Cerebral small vessel disease may be related to vascular and nonvascular pathology. We assessed whether lacunar infarcts and white matter lesions on MRI increased the risk of vascular and nonvascular death and future vascular events in patients with atherosclerotic disease. Methods— Brain MRI was performed in 1309 patients with atherosclerotic disease from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Infarcts were scored visually and volumetric assessment of white matter lesion was performed. Patients were followed for a median of 4.5 years (range, 0.2 to 7.1 years) for death, ischemic stroke, and ischemic cardiac complications. Results— Cox regression models showed that presence of lacunar infarcts (n=229) increased the risk of vascular (hazard ratio, 2.6; 95% CI, 1.4 to 4.9) and nonvascular death (hazard ratio, 2.7; 95% CI, 1.3 to 5.3), adjusted for age, sex, vascular risk factors, nonlacunar infarcts, and white matter lesion. These risks were similar for patients with silent lacunar infarcts. White matter lesion volume (relative to total intracranial volume) increased the risk of vascular death (hazard ratio per milliliter increase, 1.03; 95% CI, 1.01 to 1.05) and white matter lesions in the upper quintile compared with lower quintiles increased risk of ischemic stroke (hazard ratio, 2.6; 95% CI, 1.3 to 4.9). Conclusions— Cerebral small vessel disease, with or without a history of cerebrovascular disease, is associated with increased risk of death and ischemic stroke in patients with atherosclerotic disease.