Effect of White Matter Hyperintensity on Hemorrhagic and Ischemic Stroke Recurrence

brain scan MRI
brain scan MRI
Increasing white matter hyperintensity volume load may be associated with recurrent stroke after ischemic or hemorrhagic stroke, and with 1-year mortality after ischemic stroke.

Increasing white matter hyperintensity (WMH) volume load may be associated with recurrent stroke after ischemic or hemorrhagic stroke, and with 1-year mortality after ischemic stroke, according to study results published in Neurology.

Previous studies have shown that WMH, the most common brain abnormality in the elderly, is associated with intracerebral hemorrhage, with conflicting results concerning the association between WMH and stroke recurrence. The goal of the current study was to assess the effect of WMH on 1-year recurrence of hemorrhagic or ischemic stroke, as well as the mortality risk.

The prospective multicenter study involved 11 stroke centers in Korea that were participating in the Korean Nationwide Image-Based Stroke Database Project. Of the 8294 patients with ischemic stroke admitted within 7 days of symptom onset, 7101 patients were included in the analysis.

Within 1 year of index stroke, 345 patients experienced recurrent stroke (6.7% per year), including 286 patients (5.6% per year) with ischemic stroke, 28 patients (0.6% per year) with hemorrhagic stroke, 6 patients (0.1% per year) with unspecified stroke, and 25 patients (0.5% per year) with a transient ischemic attack.

For both ischemic and hemorrhagic strokes, the relative risk for stroke recurrence increased with WMH load, with relative risk rising most steeply for hemorrhagic stroke. Compared with the lowest quartile, adjusted subdistribution hazard ratios for recurrent hemorrhagic stroke were 7.32 (95% CI, 0.85-62.95) for the second quartile, 14.12 (95% CI, 1.53-130.30) for the third quartile, and 33.52 (95% CI, 3.69-304.37) for the fourth quartile (P for trend =.003). The respective adjusted HRs for recurrent ischemic stroke were 1.03 (95% CI, 0.69-1.52), 1.37 (95% CI, 0.93-2.04), and 1.61 (95% CI, 1.08-2.39).

Although the association between WMH volume and recurrent stroke was stronger for hemorrhagic stroke, the absolute risk for recurrent stroke was highest for ischemic stroke, regardless of WMH load. The absolute incidence of recurrence of ischemic stroke by quartile was higher (3.8%, 4.5%, 6.3%, and 8.2% per year by quartiles) compared with the recurrence of hemorrhagic stroke (0.1%, 0.4%, 0.6%, and 1.3% per year by quartiles).

Mortality rate 1 year after the index ischemic stroke was 10.5% (747 patients), including 204 vascular deaths and 540 nonvascular deaths. WMH volume was higher in patients who died than in those who survived (median volume percentage, 1.30 compared with 0.79; HR per 1 log unit, 1.58; 95% CI, 1.46-1.71; P <.001).

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Multivariable analysis showed that WMH volume was not related to 1-year vascular death after ischemic stroke, but only to nonvascular deaths. Adjusted HRs for nonvascular death for the third and fourth quartiles were 1.45 (95% CI, 1.05-1.99) and 1.59 (95% CI, 1.16-2.19; P for trend <.001) compared with the first quartile of WMH.

The researchers acknowledged several study limitations, including the retrospective analyses, limited generalizability (as all the participating centers were university hospitals), and missing information on history, adherence to medications, and specific causes of death.

“We found an association between increasing WMH and recurrent stroke, particularly hemorrhagic stroke, after ischemic stroke in a large image-based cohort,” concluded the researchers. They do note that although “increasing WMH [is] independently associated with 1-year mortality,” this association “appears to be related to nonvascular rather than vascular causes of death.”


Ryu WS, Schellingerhout D, Hong KS, et al. White matter hyperintensity load on stroke recurrence and mortality at 1 year after ischemic stroke. Neurology. 2019;93(6):e578-e589.