Silent cerebral microbleeds associated with arterial stiffness in an apparently healthy subject

Ochi, Namiko; Tabara, Yasuharu; Igase, Michiya; Nagai, Takayuki; Kido, Tomoko; Miki, Tetsuro; Kohara, Katsuhiko

doi:10.1038/hr.2009.13

Cited by 54 publications

(47 citation statements)

References 42 publications

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“…Several other studies have been performed in the general population investigating the association between arterial stiffness and markers of cerebral small vessel disease. 8,9,[11][12][13] Our finding that arterial stiffness is associated with WML volume is in line with these studies. 9,11,13 However, all of these studies used the brachial-ankle pulse wave velocity as a proxy for arterial stiffness.…”

Section: Discussionsupporting

confidence: 82%

“…6 -15 Some previous studies furthermore suggested that arterial stiffness may be influenced differentially by blood pressure with the strongest effects in subjects with hypertension. 1,16 Most of the aforementioned studies, however, used proxy markers for arterial stiffness, including the brachial-ankle pulse wave velocity and arterial pulse waves, 8,9,[11][12][13] or were performed in selected populations with high cardiovascular risk. 6,7,10,14,15 Carotidfemoral pulse wave velocity is considered as the "gold standard" measurement of arterial stiffness and allows direct investigation of the association between arterial stiffness and small vessel disease.…”

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confidence: 99%

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Arterial Stiffness and Cerebral Small Vessel Disease

Poels

Zaccai

Verwoert

et al. 2012

Stroke

209

133

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Background and Purpose-Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease. Methods-Overall, 1460 participants (mean age, 58.2 years) underwent aPWV measurement and brain MRI scanning. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries.Using automated MRI analysis, we obtained white matter lesion volumes. Infarcts and microbleeds were rated visually. We used linear and logistic regression models to associate aPWV with small vessel disease, adjusting for age, sex, mean arterial pressure, and heart rate and additionally for cardiovascular risk factors. Subsequently, we explored associations in strata of hypertension. Results-In the study group, higher aPWV was associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.07; 95% CI, 0.02-0.12) but not with lacunar infarcts or microbleeds. In persons with uncontrolled hypertension, higher aPWV was significantly associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.09; 95% CI, 0.00 -0.18), deep or infratentorial microbleeds (OR, 2.13; 95% CI, 1.16 -3.91), and to a lesser extent also with lacunar infarcts (OR, 1.63; 95% CI, 0.98 -2.70). No such associations were present in persons with controlled hypertension or without hypertension. Conclusions-In our study, increased arterial stiffness is associated with a larger volume of white matter lesions. (Stroke. 2012;43:2637-2642.)

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Arterial Stiffness and Cerebral Small Vessel Disease

Poels

Zaccai

Verwoert

et al. 2012

Stroke

209

133

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“…PVH was further classified into 5 grades according to a scale developed by Shinohara et al 21 and later modified and published as a guideline by the Japan Brain Dock Society, as follows: grade 0, absent or only a rim; grade 1, limited lesion-like caps; grade 2, irregular halo; grade 3, irregular margins and extension into the deep white matter; and grade 4, extension into the deep white matter and subcortical portion. PVH grade ≥2 was considered a pathological condition according to the guideline, as well as based on our previous findings indicating a greater frequency of left ventricular hypertrophy 22 and microbleeds 23 in subjects showing PVH grade ≥2 than in those with lower scores. Imaging analysis was performed by neurologists without clinical information on the subject.…”

Section: Mri and Assessment Of Silent Cerebral Damagementioning

confidence: 99%

Association of Postural Instability With Asymptomatic Cerebrovascular Damage and Cognitive Decline

Tabara

Okada

O’Hara

et al. 2015

Stroke

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Background and Purpose-Asymptomatic cerebral small-vessel disease (cSVD) in elderly individuals are potent risk factors for stroke. In addition to common clinical risk factors, postural instability has been postulated to be associated with cSVD in older frail patients. Here, we conducted a cross-sectional study to understand the possible link between postural instability and asymptomatic cSVD further, namely periventricular hyperintensity, lacunar infarction, and microbleeds, as well as cognitive function, in a middle-aged to elderly general population (n=1387). Methods-Postural instability was assessed based on one-leg standing time (OLST) and posturography findings. cSVD was evaluated by brain magnetic resonance imaging. Mild cognitive impairment was assessed using a computer-based questionnaire, and carotid intima-media thickness as an index of atherosclerosis was measured via ultrasonography. Results-Frequency of short OLST, in particular <20 s, increased linearly with severity of cSVD (lacunar infarction lesion: none, 9.7%; 1, 16.0%; >2, 34.5%; microbleeds lesion: none, 10.1%; 1, 15.3%; >2, 30.0%; periventricular hyperintensity grade: 0, 5.7%; 1, 11.5%; >2, 23.7%). The association of short OLST with lacunar infarction and microbleeds but not periventricular hyperintensity remained significant even after adjustment for possible covariates (lacunar infarction, P=0.009; microbleeds, P=0.003; periventricular hyperintensity, P=0.601). In contrast, no significant association was found between posturographic parameters and cSVD, whereas these parameters were linearly associated with OLST. Short OLST was also significantly associated with reduced cognitive function independent of covariates, including cSVD (P=0.002). Conclusions-Postural instability was found to be associated with early pathological changes in the brain and functional decline, even in apparently healthy subjects. Correspondence to Yasuharu Tabara, PhD, Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Shogoinkawaracho 53, Sakyoku, Kyoto 606-8507, Japan. E-mail tabara@genome.med.kyoto-u.ac.jp © 2014 American Heart Association, Inc. 16 has examined the association between lacunar infarction and postural instability, and no data are available on the association between microbleeds and postural instability, despite individuals with lacunar infarction and PVH being frequently complicated with microbleeds. 17Here, we conducted a cross-sectional study to understand the possible link between postural instability and asymptomatic cSVDs further-namely, PVH, lacunar infarction, and microbleeds-in a middle-aged to elderly general population. As we previously showed that individuals with mild cognitive impairment, particularly those with Alzheimer disease, were prone to instability while standing on 1 leg, 18 we attempted to gather more evidence in the present study. Methods Study SubjectsThe study subjects were 1387 apparently healthy middle-aged to elderly individuals who were consecutive participants in the medical checkup program a...

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“…Our results were partially in line with the previous findings of a close association between the PWV and CMBs. [14][15][16] However, the PWV is affected by changes in blood pressure during measurement and might not accurately reflect atherosclerosis in hypertensive patients. 8 In contrast, the CAVI is less influenced by blood pressure during measurement than is the PWV.…”

Section: Discussionmentioning

confidence: 99%

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

et al. 2012

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Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio-ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age ¼ 70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, Po0.001).In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12-2.00; P ¼ 0.006), advanced WMH (OR, 4.78; 95% CI, 1.55-14.74; P ¼ 0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16-9.81; P ¼ 0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

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Silent cerebral microbleeds associated with arterial stiffness in an apparently healthy subject

Cited by 54 publications

References 42 publications

Arterial Stiffness and Cerebral Small Vessel Disease

Arterial Stiffness and Cerebral Small Vessel Disease

Association of Postural Instability With Asymptomatic Cerebrovascular Damage and Cognitive Decline

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis

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