Association of White Matter Hyperintensity Markers on MRI and Long-term Risk of Mortality and Ischemic Stroke: The SMART-MR Study

Rashid Ghaznawi, Mirjam I Geerlings, Myriam Jaarsma-Coes, Jeroen Hendrikse, Jeroen de Bresser, UCC-Smart Study Group, Rashid Ghaznawi, Mirjam I Geerlings, Myriam Jaarsma-Coes, Jeroen Hendrikse, Jeroen de Bresser, UCC-Smart Study Group

Abstract

Objective: To determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke.

Methods: We included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease.

Results: We included 999 patients (59 ± 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2-16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26-1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01-2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05-1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03-1.42) and ischemic stroke (HR 1.28, 95% CI 1.05-1.55).

Conclusions: WMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. White Matter Hyperintensities (WMH) on…
Figure 1. White Matter Hyperintensities (WMH) on Fluid-Attenuated Inversion Recovery (FLAIR) Images With Corresponding Visualizations in the Automated Algorithm
Examples of confluent (A), periventricular (B), and deep (C) WMH on FLAIR images with the corresponding visualizations in our algorithm shown below. The deep WMH lesion (arrow) is reconstructed in the coronal view, while the periventricular and confluent WMH are viewed from a transverse perspective. Note that the coronal reconstruction of the deep WMH lesion (C) may be influenced by the slice thickness and the lesion may be more punctiform. The confluent WMH lesion in (A) showed a volume of 11.57 mL with an accompanying deep WMH volume of 0.25 mL. The periventricular WMH lesion in (B) showed a volume of 4.98 mL without any accompanying deep WMH lesions. The deep WMH lesion in (C) showed a volume of 0.02 mL with an accompanying periventricular and deep WMH volume of 2.12 and 0.49 mL, respectively.
Figure 2. Risk of Mortality and Ischemic…
Figure 2. Risk of Mortality and Ischemic Stroke in Relation to Quartiles of Periventricular or Confluent White Matter Hyperintensity (WMH) Volume at Baseline
Associations between quartiles of periventricular or confluent WMH volume and risk of all-cause death, vascular death, nonvascular death, and ischemic stroke. Results adjusted for age, sex, intracranial volume, large infarcts on MRI, lacunes on MRI, diastolic blood pressure, systolic blood pressure, diabetes mellitus, body mass index, and smoking pack-years at baseline. The lowest quartile (doi.org/10.5061/dryad.qv9s4mwd3). CI = confidence interval.
Figure 3. Risk of Mortality and Ischemic…
Figure 3. Risk of Mortality and Ischemic Stroke in Relation to Quartiles of Deep White Matter Hyperintensity (WMH) Volume at Baseline
Associations between quartiles of deep WMH volume and risk of all-cause death, vascular death, nonvascular death, and ischemic stroke. Results adjusted for age, sex, intracranial volume, large infarcts on MRI, lacunes on MRI, diastolic blood pressure, systolic blood pressure, diabetes mellitus, body mass index, and smoking pack-years at baseline. The lowest quartile (

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