Original Article
Determinants of White Matter Hyperintensity Volume in Patients with Acute Ischemic Stroke

https://doi.org/10.1016/j.jstrokecerebrovasdis.2009.05.007Get rights and content

Background

White matter hyperintensity (WMH) is a common radiographic finding in the aging population and a potent risk factor for symptomatic cerebrovascular disease. It is unclear whether WMH represents a single or multiple biological processes. We sought to investigate the extent and determinants of WMH in patients with acute ischemic stroke (AIS).

Methods

We retrospectively analyzed a prospectively enrolled hospital-based cohort of patients with AIS. WMH volume (WMHV) was measured using a previously published method with high interrater reliability based on a semiautomated image analysis program.

Results

WMHV was measured in 523 consecutive patients with stroke (mean age 65.2 years, median WMHV 8.2 cm3). In univariate linear regression analyses, individuals who were older, had elevated homocysteine (HCY) level or systolic blood pressure, or history of hypertension (all P < .0001), decreased glomerular filtration rate (P < .0002), atrial fibrillation (P < .0008), or coronary artery disease (P < .03) had significantly greater WMHV. After multivariable adjustment, only age (P < .0001) and HCY levels greater than 9 μmol/L (P < .003) remained independently associated with WMHV.

Conclusions

In patients with AIS, risk factors for WMH severity do not appear to overlap with those previously reported for population-based cohorts. Only age and higher HCY levels were independently associated with more severe WMH in patients with stroke. This suggests that some of the processes underlying WMH burden accumulation in patients with stroke may differ from those in the general population and are not simply mediated by traditional vascular risk factors.

Section snippets

Patient Selection and Characteristics

All consecutive patients 18 years of age or older who presented to the Massachusetts General Hospital Emergency Department (ED) with AIS were considered for this study. Potential subjects were ascertained by reviewing ED admission logs and then approached prospectively for consent. Inclusion criteria were: (1) symptoms of AIS with corresponding evidence of restricted diffusion, consistent with acute infarction, on diffusion-weighted MRI completed within 12 hours of symptom onset; (2) T2

Results

There were 523 consecutive patients who presented to our hospital ED for evaluation of acute stroke, consented to participate in the study, and had their WMHV measured on admission brain MRI (Table 1). Of these, 56% were men. Mean age was 65.2 ± 15.5 years; median WMHV was 8.2 cm3 (4.2-16.3 cm3).

In univariate analyses, age, dHCY, systolic blood pressure, HTN, AF, and coronary artery disease were associated with increased WMHV, whereas GFR was associated with decreased WMHV (Table 2). These

Discussion

The results of our study demonstrate that in patients with AIS, risk factors for WMH severity do not appear to overlap with those previously reported for population-based cohorts. Only age and HCY level above 9 μmol/L were independently associated with increasing WMHV. None of the common vascular risk factors previously shown to contribute to severity of WMH in the population-based studies (including impaired renal function, HTN, or AF) were associated independently with more severe WMH in

Summary

Despite having a large burden of WMH, patients with AIS did not demonstrate that most of the traditional vascular risk factors play an independent role in determining the severity of WMH. Instead, only age and HCY were independently associated with WMHV. These data raise the possibility that the processes underlying WMH burden accumulation in patients with stroke may differ from those in the general population. Twin and family studies of WMH in the general and HTN populations suggest that as

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    Supported by Bugher Foundation–American Stroke Association; National Institutes of Neurological Disorders and Stroke (R01 NS04217); and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke.

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