Implication of white matter hyperintensity on the long-term mortality in patients with cryptogenic stroke

Abstract

Background: Etiology of a quarter to fifth of ischemic strokes is unknown despite extensive evaluations. Although mortality rate is substantially high in cryptogenic strokes (CS), little is known regarding the factors associated with long-term mortality in patients with CS. The white matter hyperintensity (WMH) is prevalent in ischemic stroke. The risk of death is increased when the patients have WMH. We investigated the association of WMH with the long-term mortality in patients with CS.

Methods: During a 6.5-year period (January 2001-June 2007), consecutive patients with CS were enrolled and followed up until December 2013. Long-term mortality and causes of death were identified using death certificates from the Korean National Statistical Office, medical records, or interview. The presence of WMH was determined in the fluid attenuation inversion recovery magnetic resonance imaging (MRI) by two independent investigators who were blinded to the clinical information. The WMH was categorized into three groups according to Fazekas’ scale; Fazekas 0 (no WMH), Fazekas 1 to 2 (mild WMH), and 3 to 6 (severe WMH). The total Fazekas scale was calculated by adding the periventricular WMH and deep WMH scores.

Results: During the study period, 2732 consecutive patients with first-ever ischemic stroke were registered to the Yonsei Stroke Registry. Among them, 599 (21.9%) patients were classified as CS. After excluding 104 patients who underwent MRI in other hospitals, 495 patients were finally enrolled and followed-up for a median of 8.1 years (IQR, 6.6-9.5). Severe WMH was found in 192 (38.8%) patients. During the follow-up period, 158 (31.9%) patients died. The Kaplan-Meier survival analysis showed that the CS patients with severe WMH showed higher long-term mortality compared to those without. The Cox regression analysis revealed that severe WMH along with age, diabetes mellitus, initial stroke severity were independent predictors for long-term mortality. The CS patients with severe WMH had a higher death rate compared to those without (HR 1.62, 95% CI, 1.14-2.31). Subgroup analysis according to age revealed the younger patients (age < 65) with severe WMH were associated with higher death rate compared to younger patients with no or mild WMH (HR 3.45, 95% CI, 1.82-6.55).

Conclusion: In this study, we demonstrated that severe WMH was independently associated with long-term mortality in CS patients, especially in younger patients.