Elsevier

Atherosclerosis

Volume 265, October 2017, Pages 179-183
Atherosclerosis

Cerebral white matter hyperintensity is associated with intracranial atherosclerosis in a healthy population

https://doi.org/10.1016/j.atherosclerosis.2017.09.010Get rights and content

Highlights

  • ICAS is closely associated with the burden of WMH even in a healthy population.

  • Vascular risk factors may be pathophysiologic connectors between ICAS and WMH.

  • Classifying high-risk group and strict control of vascular risk factors would be helpful in preventing WMH development.

Abstract

Background and aims

Cerebral white matter hyperintensity (WMH) is commonly found in ischemic stroke patients, especially when accompanied by intracranial atherosclerosis (ICAS). However, the relationship between WMH and ICAS in a healthy population has not been evaluated.

Methods

A total of 3159 healthy subjects who underwent health checkups, including brain magnetic resonance imaging and angiography, were enrolled. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels on magnetic resonance angiography. Volumes of WMH were quantitatively rated.

Results

Eighty-two (2.6%) subjects had ICAS. The mean age of the cohort was 56 years, and the median volume of WMH was 1.02 [0.20–2.60] mL. In a multivariate analysis, ICAS [β = 0.331, 95% confidence interval (CI) = 0.086 to 0.576, p = 0.008] was significantly associated with WMH volumes after adjusting confounders. Age (β = 0.046, 95% CI = 0.042 to 0.050, p < 0.001), hypertension (β = 0.113, 95% CI = 0.017 to 0.210, p = 0.021), and diabetes (β = 0.154, 95% CI = 0.043 to 0.265, p = 0.006) were also significant, independently of ICAS. The ICAS (+) group had more frequent vascular risk factors including hypertension, diabetes, and statin use, than the ICAS (−) group, and these tendencies increased when WMH was accompanied by ICAS.

Conclusions

ICAS is associated with larger WMH volume in a healthy population. Close observation of this group and strict control of vascular risk factors are needed.

Introduction

Cerebral white matter hyperintensity (WMH) is a pathologic marker that represents tissue rarefaction or myelin pallor arising from a loss of axons or mild gliosis [1]. It is often found in elderly people, notably in those who have vascular risk factors for symptomatic cerebrovascular diseases [2]. Although the exact pathophysiologic mechanisms of WMH are unknown, it has been thought to have a similar pathophysiologic mechanism as lacunar infarction, being different from large artery disease [3], [4], [5].

Recently, many studies have shown that WMH commonly coexists in ischemic stroke patients who have large artery disease, especially intracranial atherosclerosis (ICAS) [2], [6], [7]. Increased blood-brain barrier permeability, resulting from endothelial dysfunction, and hypoperfusion, resulting from large vessel occlusion, have been suggested, although there is still a lack of conclusive evidence [8], [9]. Additionally, the relationship between WMH and large artery disease in a healthy population is still unproved.

WMH is a poor prognostic marker of stroke outcomes in many conditions [10], [11], [12]. Thus, it is important to understand the pathophysiology of WMH development. In this study, we aimed to evaluate the association between WMH and ICAS in a healthy population, relatively less affected by previous ischemic insults.

Section snippets

Patients and population

Participants, who visited the Seoul National University Hospital Health Promotion Center between January 2006 and December 2013 to undergo a voluntary routine health check-up, including brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), were consecutively enlisted (n = 3259). Among them, subjects who had reported a history of stroke or a severe neurological deficit were excluded (n = 61). Participants with severe extracranial atherosclerosis in the carotid artery

Results

We included a total of 3159 participants (mean age 56 years, males 54%). The baseline characteristics of the cohort are presented in Table 1. The median WMH volume was 1.02 [0.20–2.60], and 82 subjects had ICAS (2.6%). In univariate analysis, age, hypertension, diabetes, current smoking, systolic/diastolic blood pressure, hemoglobin A1c, fasting glucose, low-density lipoprotein cholesterol, ICAS, anti-platelet agent use, anti-hypertensive use, and statin use were significantly associated with

Discussion

In this study, we found that the presence of ICAS was associated with the volume of WMH even in a healthy population. The frequency of ICAS in the cohort was 2.6%, which is not much different from that in a previous study performed in a healthy population [17].

We have several possible explanations for these results. First, diffuse hypoperfusion resulting from ICAS may play a role. The pathophysiologic mechanism of WMH is not well known, and it is thought to be complex. However, the roles of

Conflict of interest

The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Author contributions

Conceptualization: K.W.-N.; H.M.-K; J.H.-P. Data curation: K.W.-N.; H.Y.-J.; S.H.-K.

Formal analysis: K.W.-N.; S.M.-J,; T.G.-Y. Writing: K.W.-N.; S.H.-K. Supervision: H.M.-K.; J.H.-P.

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