Cerebral white matter hyperintensity is associated with intracranial atherosclerosis in a healthy population
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.
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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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2022, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :The association of leukoaraiosis and aICAS remains controversial. Our findings differ from the hypothesis that hypoperfusion resulting from large vessel occlusion may affect the severity of leukoaraiosis,34 but one Korean study of 3159 healthy participants found that ICAS is associated with a larger WMHV,35 whereas a study in patients with acute ischemic stroke from Massachusetts General Hospital did not show a relationship between large artery stenosis and WMH lesion burden,36 which is consistent with our findings. This study further supports WMH as a manifestation of CSVD and compared with severe occlusive/stenotic disease of the large extra- or intracranial artery, arterial stiffening results in increased aortic pulsatility, and its transmission to the cerebral circulation may be the primary causes of WMH.6–9
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These authors contributed equally as corresponding authors.