White Matter Hyperintensities and Recurrent Stroke Risk in Stroke Patients With Small-Vessel Disease Burden

Abstract

Background and Purpose: Although white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are linked to an increased risk of infarct growth, the impact of WMH severity on the long-term risk of recurrent stroke is currently unknown. This study aimed to evaluate the association between WMH severity and the risk of recurrent vascular events among ischemic stroke patients with small-vessel disease (SVD). Methods: Data from participants (n = 1,454) in the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral HemOrrhage trial were reviewed. The severity of WMH in baseline brain MRI scans was assessed using the Fazekas scale. The association between WMH severity and stroke (ischemic or hemorrhagic) and major vascular events (MVEs, a composite of stroke, myocardial infarction, or vascular death) was assessed. Results: Study patients were having significant burden of SVD; Fazekas score 0 (n=2), 1 (n = 426), 2 (n = 650), and 3 (n = 376) and median Fazekas scale was 2 (mean follow-up 1.9 ± 1.3 years). The stroke incidence rate per 100 person-years was 2.6% in the Fazekas 0-1 group, 3.6% in Fazekas 2, and 7.0% in Fazekas 3, and the rates for MVEs were 3.3%, 4.3%, and 7.6%, respectively. Compared with the Fazekas 0-1 group, the Fazekas 3 group was associated with a higher risk of stroke (adjusted hazard ratio, 2.69; 95% confidence interval, 1.61–4.50; P < 0.001), ischemic stroke (2.56; 1.44–4.55; P = 0.001), hemorrhagic stroke (3.26; 1.04–10.25; P = 0.043), and MVEs (2.27; 1.43–3.61; P = 0.001). Conclusions: In this study of Asian patients with SVD who had experienced a non-cardioembolic stroke or transient ischemic attack, advanced WMH (Fazekas 3) was independently associated with a greater than 2-fold increased risk of recurrent stroke during the 2-year follow-up period, when compared with the milder WMH group (Fazekas ≤ 1). Increasing WMH severity may, therefore, be a useful prognostic indicator of patients at high risk of recurrent vascular events.