title: Extensive white matter changes predict stroke recurrence up to 5 years after a first-ever ischemic stroke.
abstract: BACKGROUND
  White matter changes (WMCs), a surrogate for small-vessel disease (SVD), have been shown to be associated with a major negative influence on cognition, mood and functioning in daily life. We aimed to investigate whether severe WMCs are a risk factor for recurrent ischemic stroke in a long-term follow-up.
  
  
  METHODS
  320 consecutive patients admitted to hospital with a first-ever ischemic stroke were included in the study and followed up for 12 years using extensive national registers. Patients were aged between 55 and 85 years, with a mean age of 70.8 years. WMCs were rated using MRI and stratified into two grades: absent to moderate WMCs versus severe WMCs. Univariate analysis was performed using binary logistic regression analysis, Kaplan-Meier log rank analysis and life table function. To control for factors such as age, education and cardiovascular risk factors, a multivariate Cox regression proportional hazards analysis was made with forced entry.
  
  
  RESULTS
  At least one recurrent stroke, nonfatal or fatal, was diagnosed in 76 (23.8%) patients at 5 years and in 127 (39.7%) patients at 12 years. In univariate analysis, only advancing age was associated with WMCs. The cumulative 5-year recurrence risk was 24.5% [95% confidence interval (95% CI) 23.8-25.2] for patients with absent to moderate WMCs and 39.1% (95% CI 38.1-40.1) for patients with severe WMCs. The cumulative 12-year recurrence risk was 48.1% (95% CI 45.5-50.7) for patients with absent to moderate WMCs and 60.9% (95% CI 56.7-65.1) for patients with severe WMCs. In Cox regression proportional hazards analysis, independent predictors of recurrent stroke at 5 years were severe WMCs [hazard ratio (HR) 1.80, 95% CI 1.11-2.95], atrial fibrillation (HR 1.81, 95% CI 1.09-3.02), hypertension (HR 1.69, 95% CI 1.05-2.71) and peripheral arterial disease (HR 1.89, 95% CI 1.06-3.38). At 12 years, only increasing age remained as an independent predictor (HR 1.04, 95% CI 1.02-1.07). In receiver operating characteristic analysis, the area under the curve for severe WMCs was 0.58 (95% CI 0.51-0.65) for the prediction of stroke recurrence within 5 years.
  
  
  CONCLUSIONS
  In our well-defined cohort of poststroke patients, the presence of severe WMCs was an indicator of stroke recurrence up to 5 years after a first-ever ischemic stroke. WMCs can be considered as an SVD marker that summarizes the effects of several classical risk factors on the small-vessel brain network and therefore can be used as a score for risk stratification of stroke recurrence. Our findings further underline the poor long-term prognosis of cerebral SVD.
authors.affiliation: Department of Neurological Sciences, University of Helsinki, and Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. susanna.melkas@hus.fi
authors.forename: S
authors.initials: S
authors.lastname: Melkas
authors.forename: G
authors.initials: G
authors.lastname: Sibolt
authors.forename: N K J
authors.initials: NK
authors.lastname: Oksala
authors.forename: J
authors.initials: J
authors.lastname: Putaala
authors.forename: T
authors.initials: T
authors.lastname: Pohjasvaara
authors.forename: M
authors.initials: M
authors.lastname: Kaste
authors.forename: P J
authors.initials: PJ
authors.lastname: Karhunen
authors.forename: T
authors.initials: T
authors.lastname: Erkinjuntti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*