Risk of Vascular Events after Nondisabling Small and Large Vessel Cerebral Ischemia

Abstract

Background: Small- and large-vessel disease (SVD and LVD, respectively) might have a different pathogenesis and prognosis but the long-term risk of death and recurrent stroke appears to be similar in previous studies. In this study, we investigated the long-term vascular prognosis of patients with LVD and SVD in a large cohort of well-documented patients. Methods: We included 971 patients with transient ischemic attack (TIA) or nondisabling ischemic stroke of atherosclerotic origin referred to a university hospital in the Netherlands between 1994 and 2005 and followed them for the occurrence of vascular events or death. The primary outcome was a composite of stroke, myocardial infarction and vascular death, whichever happened first. Classification of SVD/LVD was primarily based on brain imaging. We used regression analyses to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were performed in subsets of the population, i.e. patients with subtype classification based on imaging, excluding TIA patients, first-ever stroke patients and LVD patients without a symptomatic carotid stenosis. Results: During a mean follow-up of 6.3 years, new vascular events occurred in 56 of 312 SVD patients (3.3%/year) and in 128 of 659 LVD patients (2.9%/year). These were ischemic strokes in 33 of the 56 events in SVD patients (2.0%/year) and 54 of the 128 events in LVD patients (1.2%/year). The corresponding age- and sex-adjusted HR for all new vascular events for LVD versus SVD was 0.76 (95% CI 0.56-1.05) for the total follow-up period. When this risk was split into early risk (<1 year) and late risk (>1 year), it was not significantly different for the 1-year risk of vascular events (HR 1.04, 95% CI 0.57-1.91); however, after 1 year of follow-up, LVD patients had fewer outcome events compared with SVD patients (HR 0.66, 95% CI 0.46-0.96). For ischemic strokes, the overall HR was 0.60 (95% CI 0.39-0.94). As with the primary outcome, here also the 1-year risk was not significantly different from >1-year risk (HR 1.31, 95% CI 0.62-2.81, and HR 0.36, 95% CI 0.21-0.63, respectively). The sensitivity analyses showed virtually the same results. Conclusion: In patients with nondisabling cerebrovascular disease, we found, despite no differences at baseline in terms of vascular risk factors, a better long-term prognosis for patients with LVD for all vascular events, especially for recurrent strokes. Our observations support a different pathogenesis in SVD and LVD patients, and optimal prevention is indicated for patients with what was formerly regarded as ‘benign' SVD stroke.