Shuhei Okazaki

Osaka University, Suika, Ōsaka, Japan

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Publications (29)124.14 Total impact

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    ABSTRACT: The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined.
    European Journal of Neurology 08/2014; · 4.16 Impact Factor
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    ABSTRACT: Limited information is available on the long-term effects of interleukin-6 (IL-6) on systemic atherosclerosis. The purpose of the present study was to clarify the relationship between chronic elevation of IL-6 and the long-term progression of carotid atherosclerosis.
    08/2014;
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    ABSTRACT: To investigate whether cerebral microbleeds (CMBs) are independently associated with incident dementia in patients with vascular risk factors.METHODS: Using data from a Japanese cohort of participants with vascular risk factors in an observational study from 2001, we evaluated the association between CMBs at baseline and incident dementia. Baseline brain MRI was used to determine small-vessel disease (CMBs, lacunar infarcts, and white matter hyperintensities) and brain atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings.RESULTS: Of the 524 subjects (mean age 68 ± 8.3 years, 57.6% male, 12.8 ± 2.6 years of schooling, 21.6% CMBs), 44 patients with incident dementia (20 Alzheimer disease, 18 vascular dementia, 3 mixed-type, and 3 other) were diagnosed during the median 7.5-year follow-up. In multivariate analysis, the presence of overall CMBs was not associated with an increased risk of incident all-cause dementia (p = 0.15). However, multiple CMBs (≥2) or mixed (lobar and deep) CMBs were associated with the increased risk of all-cause dementia, whereas strictly lobar CMBs showed no association with any dementia.CONCLUSIONS: Multiple CMBs or mixed CMBs independently showed higher risk of all-cause dementia. Our results reinforce the hypothesis that CMBs exert deleterious effects on dementia incidence, suggesting that this association may be mediated by vascular burden.
    Neurology 07/2014; · 8.30 Impact Factor
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    ABSTRACT: Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (ie, a systolic blood pressure ≥140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, -1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6-10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant.
    Hypertension 03/2014; · 6.87 Impact Factor
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    ABSTRACT: To determine whether chronic kidney disease (CKD) is associated with incident dementia independent of cerebral small-vessel disease (SVD) in patients with vascular risk factors. Using data from a Japanese cohort of participants with vascular risk factors in an ongoing observational study from 2001, we evaluated the association between CKD at baseline and incident dementia. Baseline brain MRI was used to determine SVD (lacunar infarction, white matter hyperintensities), medial-temporal atrophy, and subcortical atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings. Of the 600 subjects (mean age 68 ± 8.3 years, 57% male, 12.8 ± 2.6 years of education; CKD: 29%), 50 patients with incident dementia (Alzheimer disease: 24; vascular dementia: 18; mixed-type dementia: 5; other types: 3) were diagnosed during the median 7.5-year follow-up. CKD at baseline was associated with an increased risk of all-cause dementia in models adjusted for age, sex, educational level, and APOE ε4 allele. The associations of CKD at baseline remained significant even after additional adjusting for MRI findings and confounding variables (hazard ratio: 1.96 [1.08-3.58], p = 0.026). CKD is independently related to the risk of all-cause dementia in patients with vascular risk factors. Our results reinforce the hypothesis that CKD exerts deleterious effects on dementia incidence.
    Neurology 02/2014; · 8.30 Impact Factor
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    ABSTRACT: The risk of neurological deterioration during valve surgery using cardiopulmonary bypass under systemic heparinization in infective endocarditis (IE) patients with intracranial haemorrhage (ICH) is unknown. The objective of this retrospective study was to investigate the stratified risk related to the timing of valve surgery on neurological outcomes in patients with active IE and preoperative ICH. From 2004 to 2012, 246 patients underwent valve surgery for IE in hospitals enrolled in the Osaka Cardiovascular Research Group. Of these, a group of 30 patients had preoperative ICH, and they included 18 patients with cerebral haemorrhage, 8 with subarachnoid haemorrhage and 4 with haemorrhagic infarction. The preoperative characteristics, neurological statuses and postoperative results of these patients were retrospectively explored to analyse the effects of the timing of surgery on neurological outcomes. Twenty-one patients had symptomatic ICH, and the median modified Rankin score was 1.5 (95% confidence interval [CI] 1.2-2.8). Eight patients were diagnosed with mycotic aneurysms, and 7 of these patients underwent aneurysm resection or clipping before valve surgery. All 30 patients underwent valve surgery, and the median interval between ICH onset and surgery was 22.5 (95% CI 15.5-39.4) days. Four patients died of multiple organ dysfunction or heart failure. The interval between ICH onset and valve surgery was within 7 days for 5 cases, between 8 and 14 days for 6, between 15 and 28 days for 9 and >29 days for 10. Postoperative neuroimaging showed that neither neurological deterioration nor exacerbation of haemorrhagic lesions had occurred among the 30 patients, regardless of the timing of surgery. However, 2 cases who underwent valve surgery 8 and 81 days after the onset of ICH developed new ectopic asymptomatic haemorrhages postoperatively. The risk of postoperative neurological deterioration resulting from the exacerbation of haemorrhagic lesions seemed relatively low, even in IE patients who underwent valve surgery within 2 weeks of ICH onset. However, further evaluation of the sizes and aetiologies of haemorrhagic lesions is vital to establish a safe interval between the ICH onset and surgery.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 01/2014; · 2.40 Impact Factor
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    ABSTRACT: Aim: Patients with gynecological neoplasms often suffer ischemic stroke. This study aimed to clarify the underlying mechanisms of ischemic stroke in patients with gynecological tract tumors. Methods: We retrospectively reviewed 6 patients with gynecologic tumors and hypercoagulability who were being treated for acute ischemic stroke between 2006 and 2012. Diffusion-weighted magnetic resonance imaging (DW-MRI), cardiovascular risk factors including plasma D-dimer levels, and histologic examination of the patients' solid tumors were performed. All 6 patients underwent transesophageal echocardiography (TEE) for nonbacterial thrombotic endocarditis (NBTE) and paradoxical embolism. Results: All 6 patients showed elevated plasma D-dimer levels. In 1 patient, paradoxical embolism was diagnosed. In the remaining 5 patients, DW-MRI scans showed numerous lesions in multiple vascular territories, and in 4 of these 5 patients, TEE demonstrated vegetations on the mitral valve, leading to the diagnosis of NBTE. Interestingly, 2 of these 4 patients had benign uterine tumors, whereas the other 2 had ovarian cancer. Conclusions: NBTE was the main etiology for ischemic stroke in patients with gynecologic tract tumors and coagulopathy. Both malignant and benign tumors of the gynecologic tract can cause NBTE. © 2013 S. Karger AG, Basel.
    European Neurology 09/2013; 70(5-6):304-307. · 1.50 Impact Factor
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    ABSTRACT: OBJECTIVE: Basilar arterial (BA) dolichoectasia is associated with cerebral small-vessel disease and stroke. However, the association between moderate dilation of the BA and cerebral small-vessel disease or subsequent cardiovascular events remains unclear. This study aims to clarify the factors related to BA diameter and to clarify whether the BA diameter is an independent predictor of cardiovascular events. APPROACH AND RESULTS: The study subjects comprised 493 outpatients with atherosclerotic risk factors. BA diameter, lacunar infarct, severity of deep white matter hyperintensities, and intracranial steno-occlusive lesions were assessed with MRI and magnetic resonance angiography. Then, we prospectively evaluated the association between BA diameter and cardiovascular events. The BA diameter ranged from 1.1 to 5.2 mm, and only 0.8% of the patients had dolichoectasia. Male sex, the presence of lacunar infarcts, the severity of deep white matter hyperintensities, the fetal-type variation of the circle of Willis, and intracranial steno-occlusive lesions were independently associated with BA diameter. In the mean follow-up of 6.0 years, 91 patients developed cardiovascular events. BA diameter was independently associated with total cardiovascular events after adjusting for age, sex, and conventional risk factors (hazard ratio, 1.55 per 1 mm increase in BA diameter; P=0.009). CONCLUSIONS: Increased BA diameter within the normal range is related to both large-vessel disease and cerebral small-vessel disease, and it could be a new predictor of cardiovascular events.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2013; · 6.34 Impact Factor
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    ABSTRACT: AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.
    Diabetologia 04/2013; · 6.49 Impact Factor
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    ABSTRACT: Background: Acute brain infarction affects the timing and regimen of cardiac surgery in patients with infective endocarditis (IE). We aimed to identify preoperative brain MRI characteristics, incidence, and related factors for acute ischemic lesions in left-sided IE patients undergoing cardiac surgery. Furthermore, we investigated whether preoperative acute ischemic lesions are associated with postoperative neurological complications in IE patients. Methods: We retrospectively reviewed consecutive patients with a definite left-sided IE who underwent cardiac surgery in 6 university-affiliated hospitals from January 2004 to November 2011. Preoperative brain MRI evaluations were systematically performed on all patients without contraindications, regardless of neurological complications, with the aim of preventing perioperative complications. Patients were included if diffusion-weighted imaging and fluid-attenuated inversion recovery sequences were performed within 14 days after diagnosis. Associations between acute ischemic lesions and related factors were analyzed. Neurological complications within 30 days after surgery were evaluated for postoperative outcome analyses. Results: Of 139 consecutive patients with left-sided IE who underwent cardiac surgery, 85 patients were evaluated in this study. The mean age was 58 ± 16 years, and 22 patients (26%) were women. Preoperative MRI revealed acute ischemic lesions in 47 patients (55%), and 19 of these patients developed neurological symptoms. Among the patients with ischemic lesions, 24 (60%) had small lesions (<10 mm), 36 (77%) had multiple lesions, and 30 (64%) had lesions in multiple vascular territories. Compared to patients without ischemic lesions, patients with acute ischemic lesions were older and had significantly higher white blood cell counts and plasma C-reactive protein (CRP) levels, but lower hemoglobin levels. Logistic regression analyses showed that the white blood cell count and plasma CRP level were independently associated with acute ischemic lesions [adjusted OR per 1-SD increase were 2.21 (95% CI: 1.23-4.35) and 2.33 (95% CI: 1.27-4.96), respectively]. Three patients developed postoperative neurological complications, but preoperative acute ischemic lesions and postoperative complications were not associated. Conclusions: Preoperative MRI detected a high incidence of asymptomatic ischemic lesions in IE patients. Acute ischemic lesions were often small, multiple, and located in multiple vascular territories. Inflammatory reactions may play an important role in the development of ischemic lesions in IE patients.
    Cerebrovascular Diseases 02/2013; 35(2):155-162. · 2.81 Impact Factor
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    ABSTRACT: Background: Plasma D-dimer level may reflect the activity of thrombus formation in the left atrium of patients with nonvalvular atrial fibrillation (NVAF). Proper anticoagulation with warfarin dramatically decreases the rate of cerebral embolism, reduces stroke severity and subsequent risk of death, as well as the level of D-dimer in NVAF patients. However, the predictive value of D-dimer level on cerebral embolism severity has not been examined. Thus, the purpose of this study was to investigate the association between plasma D-dimer level at admission and infarct size in NVAF patients. Methods: We identified 124 patients with consecutive ischemic stroke and NVAF who were admitted within 48 h of symptom onset. We measured infarction volume from CT taken after 3 ± 1 days from the onset. Plasma D-dimer levels were measured at the time of admission. Relationships were analyzed between infarction volume and plasma D-dimer levels, cardiovascular risk factors, preadmission medications and admission conditions. We also assessed the influence of D-dimer level on functional outcome in patients with preadmission modified Rankin Scale (mRS) score of 0-1 and patients by tertile of D-dimer level (≤0.83, 0.83-2.16 and ≥2.16 µg/ml). Results: Infarction volume significantly correlated with D-dimer level (r = 0.309, p < 0.001), systolic blood pressure (r = 0.201, p = 0.026), diastolic blood pressure (r = 0.283, p = 0.002), National Institutes of Health Stroke Scale (NIHSS) score on admission (r = 0.546, p < 0.001) and mRS score at discharge (r = 0.557, p < 0.001). Multivariate regression analyses showed that the D-dimer level was significantly associated with infarction volume after adjusting for age, sex, current smoker or not, prothrombin time-international normalized ratio ≥1.6, diastolic blood pressure, CHADS(2) score and NIHSS score on admission. In patients with a preadmission mRS score of 0-1 (n = 108), D-dimer level was significantly associated with NIHSS score at admission (r = 0.318, p < 0.001) and mRS score at discharge (r = 0.310, p = 0.001). Patients in the highest D-dimer tertile group showed worse outcome than those in the middle (p = 0.041) and lowest (p < 0.001) tertiles. Conclusions: Plasma D-dimer level on admission is significantly related to infarction volume and functional outcome, following cardioembolic stroke in NVAF patients.
    Cerebrovascular Diseases 01/2013; 35(1):64-72. · 2.81 Impact Factor
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    ABSTRACT: OBJECTIVE: The objective of this study was to examine the association of inflammatory markers with risk of first-ever cerebrovascular events (CVEs), while simultaneously evaluating subclinical vascular disease. METHODS AND RESULTS: We enrolled 464 outpatients who had vascular risk factors without any preexisting cardiovascular disease. We examined the presence of silent lacunar infarction (SLI) by magnetic resonance imaging; carotid intima-media thickness by ultrasound; and measured high-sensitivity C-reactive protein, interleukin (IL)-6, and IL-18 at baseline, and assessed their associations with CVEs using Cox proportional hazards models of 4.8±2.6 years follow-up. We further calculated measures of reclassification and discrimination. In age- and sex-adjusted analysis, IL-6, but neither high-sensitivity C-reactive protein nor IL-18, was associated with CVEs. The association remained significant after adjustment for conventional risk factors, intima-media thickness, and SLI (hazard ratios: 1.80, per 1-SD increase in log IL-6, P=0.03). Compared with the patients with below median IL-6 without SLI, those with above median IL-6 and SLI had a higher risk of CVEs (hazard ratios: 4.14, P=0.0014). The combination of IL-6 and SLI resulted in the net reclassification improvement of 14.3% (P=0.04), and the integrated discrimination improvement gain of 2.1% (P=0.05). CONCLUSIONS: IL-6 levels were independently associated with CVEs and could improve reclassification in those with SLI.
    Arteriosclerosis Thrombosis and Vascular Biology 11/2012; · 6.34 Impact Factor
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    ABSTRACT: The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. We included 14 population-based cohorts contributing data for 45,828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
    JAMA The Journal of the American Medical Association 08/2012; 308(8):796-803. · 29.98 Impact Factor
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    ABSTRACT: We report a case of internal carotid artery (ICA) occlusion caused by arterial dissection triggered by an elongated styloid process. A 43-year-old man presented with a headache followed by speech disturbance. Magnetic resonance imaging and magnetic resonance angiography scans revealed acute infarction and right ICA occlusion. A T1-weighted magnetic resonance imaging scan revealed a hyperintensity in the occluded ICA, suggesting intramural hematoma. Computed tomographic angiography also revealed ICA occlusion and bilateral elongated styloid processes. We performed transoral carotid ultrasonography, which revealed the absence of flow signal in the double lumen of the dilated extracranial ICA. We diagnosed his condition as arterial dissection and treated him with antithrombotic drugs. Six months later, the occluded ICA recanalized spontaneously, and computed tomographic angiography at that time revealed a close relation between the tip of the styloid process and the recanalized ICA. This finding suggests that an elongated styloid process is involved in arterial dissection. In patients with ICA occlusion of unknown etiology, an evaluation for intramural hematoma and styloid process length are useful for the diagnosis of dissection and its etiology.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 06/2012;
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    ABSTRACT: The optimal timing of surgical intervention for infective endocarditis (IE) with cerebrovascular complications remains controversial because the risk of perioperative intracranial hemorrhage is still unclear. The aim of this study was to investigate the prevalence of acute cerebral infarction (CI) in patients with IE and its hemorrhagic risk after valve operations. We retrospectively evaluated 102 consecutive patients (35 with neurologic symptoms; 67 without neurologic symptoms) who underwent diffusion-weighted magnetic resonance imaging (DW-MRI) before valve operations for left-sided active IE between 2005 and 2010. The prevalence of acute CI and its postoperative neurologic outcome were evaluated. Acute CI was detected preoperatively in 64 of 102 (62.7%) patients. Of the 64 patients with acute CI, 34 underwent surgical treatment within 14 days after diagnosis of CI (early group), whereas the other 30 patients underwent operation after more than 14 days (delayed group). Postoperative CI deterioration was confirmed in 1 patient in each group. Furthermore, in 43 of the patients with acute CI who were followed with postoperative neuroimaging, hemorrhagic transformation was confirmed in only 1 patient in the delayed group. However new ectopic intracranial hemorrhage was confirmed in 2 patients in the early group and 3 patients in the delayed group. The risk of postoperative hemorrhagic transformation of preoperative acute CI was low, even in patients who underwent early operation. Our data suggested that there is no benefit for delaying surgical treatment beyond 2 weeks to prevent hemorrhagic transformation in patients with CI. However ectopic intracranial hemorrhage sometimes occurs regardless of the timing of surgical treatment.
    The Annals of thoracic surgery 06/2012; 94(2):489-95; discussion 496. · 3.45 Impact Factor
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    ABSTRACT: Echolucent plaques are associated with high risk of ischemic cerebrovascular events. Oxidative stress has been implicated in the process of atherosclerotic plaque development from initiation to progression. We assessed the relation between carotid plaque echogenicity and urinary 8-iso-prostaglandin F2α, as an index of oxidative stress. This cross-sectional study was conducted prospectively on 290 consecutive outpatients. Each patient was evaluated for carotid plaque echogenicity using the gray-scale median at the maximal thickness plaque and urinary 8-iso-prostaglandin F2α using enzyme linked immunosorbent assay. By Pearson correlation analysis, we found significant negative linear relation between gray-scale median values and the urinary 8-iso-prostaglandin F2α levels (r = -0.133, p = 0.023). This correlation remained significant after adjustment for atherosclerotic risk factors, thickness of the maximal plaque and medication use (β = -0.137, p = 0.031). We herein show that higher levels of urinary 8-iso-prostaglandin F2α is associated with lower plaque echogenicity.
    Ultrasound in medicine & biology 03/2012; 38(3):487-91. · 2.46 Impact Factor
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    ABSTRACT: Cerebral microbleeds (CMBs) detected by T2*-weighted MRI are a potential indicator of hypertension, microvascular disease and hemorrhagic stroke. An association between infective endocarditis (IE) and CMBs has been reported recently, but the clinical significance remains unclear. We hypothesized that CMBs in patients with IE are associated with vascular vulnerabilities such as mycotic aneurysm or pyogenic vasculitis. We retrospectively reviewed 26 consecutive patients with definite IE who underwent T2*-weighted MRI and were admitted to 2 medical centers in Osaka, Japan, between January 2006 and June 2010. We examined the incidence of symptomatic intracranial hemorrhage (ICH) occurring after initial MRI examination and investigated the association between ICH, CMBs and other clinical characteristics. CMBs were identified in 14 patients (54%), and 72% of CMBs were found in the lobar region. Symptomatic ICH was observed in 8 patients (31%) during the 3-month follow-up period after initial MRI examination. In multiple logistic regression analyses, the presence of preceding ICH [odds ratio (OR) 40.0, 95% confidence interval (CI) 2.5-2,870] and the presence of CMBs (OR 34.0, 95% CI 1.3-17,300) were independent predictors of the development of ICH. Using cutoff values for CMBs of ≥2 and ≥3, the adjusted ORs for ICH increased (OR 42.1, 95% CI 1.9-24,300, and OR 70.1, 95% CI 2.5-105,000, respectively). In addition to prior ICH, the presence of CMBs was a strong predictor of impending ICH in patients with IE. CMBs might represent vascular vulnerability related to IE.
    Cerebrovascular Diseases 11/2011; 32(5):483-8. · 2.81 Impact Factor
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    ABSTRACT: Cerebral microbleeds (CMB) are observed in the elderly and have been regarded as one of the manifestations of small vessel disease. Although inflammatory processes have attracted much attention not only in large-artery disease, but also in small vessel disease, their involvement in CMB remains to be determined. The purpose of this study is to clarify relations between inflammatory marker levels and CMB. Four hundred thirty-one patients without histories of cerebrovascular diseases were prospectively enrolled. The presence and number of CMB were assessed on gradient-echo magnetic resonance imaging. As common inflammatory markers, serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-18 (IL-18) were evaluated. CMB were found in 65 patients (15%). In 35 patients, at least one CMB was found in deep locations, but 30 patients had strictly lobar CMB. Levels of hsCRP, IL-6, and IL-18 were higher in patients with CMB than in those without. Logistic regression analyses showed that each 1SD increase in each inflammatory marker level was significantly associated with the presence of CMB after adjustment for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction, and white matter hyperintensity. The OR (95% CI) of hsCRP, IL-6, and IL-18 was 1.81 (1.35-2.46), 1.73 (1.18-2.61), and 2.41 (1.44-4.52), respectively. Furthermore, the inflammatory marker levels were associated with both deep and lobar CMB. Higher levels of hsCRP, IL-6, and IL-18 are associated with CMB, in both deep and lobar locations, suggesting the involvement of inflammation in CMB.
    Stroke 08/2011; 42(11):3202-6. · 6.16 Impact Factor
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    ABSTRACT: We investigated the influence of preadmission anticoagulation on infarct volume in patients with nonvalvular atrial fibrillation (NVAF). Data were collected on consecutive ischemic stroke patients with NVAF admitted to Osaka University Hospital between 2004 and 2011. Patients were divided into 3 groups: the no-anticoagulation group, the subtherapeutic anticoagulation group [admission prothrombin time international normalized ratio (PT-INR) <1.6], and the therapeutic anticoagulation group (PT-INR ≥1.6). In analyses of neurological outcome, we excluded patients with a modified Rankin Scale (mRS) score of >1 before onset. Of the 68 patients, 45 were classified into the no-anticoagulation group, 9 into the subtherapeutic group, and 14 into the therapeutic group. The median value of infarct volume was 60 (interquartile range 9-176), 142 (64-184), and 8 (3-46) ml in each group, respectively. Infarct volume in the therapeutic group was significantly smaller than in the subtherapeutic group (p = 0.010), and tended to be smaller than in the no-anticoagulation group (p = 0.086). National Institute of Health Stroke Scale score at admission, and mRS score at discharge were significantly reduced in the therapeutic group compared with those in the other groups (p = 0.028 and p = 0.017, respectively). Therapeutic anticoagulation reduces infarct volume and improves neurological outcome after ischemic stroke in patients with NVAF.
    European Neurology 01/2011; 66(5):277-82. · 1.50 Impact Factor
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    ABSTRACT: This study investigated whether plasma D-dimer level is useful for detection of deep vein thrombosis (DVT) in patients with acute stroke. A total of 133 patients hospitalized within 3 days after stroke onset underwent duplex venous ultrasonographic examination of the lower limbs and repeated measurements of plasma D-dimer level. DVT was detected in 36 of 100 patients with ischemic stroke and in 25 of 33 patients with intracerebral hemorrhage (ICH) (76%; P < .001). Plasma D-dimer level on admission (7.5 ± 10.7 μg/mL vs 3.7 ± 10.1 μg/mL; P = .040) and its maximum level before the ultrasonographic examination (29.1 ± 48.7 μg/mL vs 5.5 ± 11.0 μg/mL; P < .001) were higher in the patients with DVT compared with those without DVT. On multivariate logistic regression analysis, the maximum D-dimer level was independently related to the identification of DVT (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09 per 1-μg/mL increase; P = .045), but the admission D-dimer level was not when it was included instead of the maximum D-dimer level. In addition, female sex (OR, 4.99), ICH (OR, 5.20), high Wells clinical score (OR, 2.40 per 1-point increase), and low protein level (OR, 0.21 per 1-g/dL increase) were independently related to the identification of DVT. The optimum cutoff value of the maximum D-dimer level for positive DVT was 5.5 μg/mL (sensitivity, 89%; specificity, 82%). Our findings suggest that high plasma D-dimer level during the course of acute stroke can help detect DVT on duplex venous ultrasonography.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 08/2010; 21(3):205-9.

Publication Stats

153 Citations
124.14 Total Impact Points

Institutions

  • 2014
    • Osaka University
      Suika, Ōsaka, Japan
  • 2009–2014
    • Osaka City University
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 2012
    • Osaka Institute of Technology
      Ōsaka, Ōsaka, Japan
  • 2007–2008
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan