WMH and long-term outcomes in ischemic stroke A systematic review and meta-analysis

Objective To investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality. Methods Following the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle-Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models. Results We included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72-2.73), cognitive impairment (RR 2.29, 95% CI 1.48-3.54), functional impairment (RR 2.21, 95% CI 1.83-2.67), any recurrent stroke (RR 1.65, 95% CI 1.36-2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26-2.88), all-cause mortality (RR 1.72, 95% CI 1.47-2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44-2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias. Conclusions Presence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials.