Takahiro Kuwashiro

Takotsubo Cardiomyopathy in Acute Ischemic Stroke

Takotsubo cardiomyopathy, which is characterized by transient left ventricular apical ballooning, is a known complication of subarachnoid hemorrhage. The aim of this study was to identify the clinical characteristics of acute ischemic stroke patients who experienced development of takotsubo cardiomyopathy.

Prestroke Glycemic Control Is Associated With the Functional Outcome in Acute Ischemic Stroke The Fukuoka Stroke Registry

Background and Purpose— Diabetes mellitus is an established risk factor for stroke. However, it is uncertain whether prestroke glycemic control (PSGC) status affects clinical outcomes of acute ischemic stroke. The aim of this study was to elucidate the association between PSGC status and neurological or functional outcomes in patients with acute ischemic stroke. Methods— From the Fukuoka Stroke Registry (FSR), a multicenter stroke registry in Japan, 3627 patients with first-ever ischemic stroke within 24 hours after onset were included in the present analysis. The patients were categorized into 4 groups based on their PSGC status: excellent (hemoglobin [Hb] A1c on admission <6.2%), good (6.2–6.8%), fair (6.9–8.3%) and poor (≥8.4%). Study outcomes were neurological improvement (≥4 points decrease in the National Institutes of Health Stroke Scale [NIHSS] score during hospitalization or 0 points on NIHSS score at discharge), neurological deterioration (≥1 point increase in NIHSS score) and poor functional outcome (death or dependency at discharge, modified Rankin Scale 2–6). Results— The age- and sex-adjusted ORs for neurological improvement were lower, and those for neurological deterioration and a poor functional outcome were higher in patients with poorer PSGC status. After adjusting for multiple confounding factors, these trends were unchanged (all probability values for trends were <0.002). These findings were comparable in patients with noncardioembolic and cardioembolic infarctions. Conclusions— In ischemic stroke patients, HbA1c on admission was an independent significant predictor for neurological and functional outcomes.

Effect of Prothrombin Complex Concentrate on Hematoma Enlargement and Clinical Outcome in Patients with Anticoagulant-Associated Intracerebral Hemorrhage

Background: The present study was carried out to determine the effect of prothrombin complex concentrate (PCC) on hematoma enlargement (HE) and the early clinical outcome of intracerebral hemorrhage (ICH) patients on long-term warfarin treatment. Methods: Themedical records and computed tomography (CT) images of 50 consecutive ICH patients on long-term warfarin treatment (35 men, 15 women; 69 ± 12 years old) were reviewed. International normalized ratio (INR) values, frequency of HE and clinical outcome were compared between patients treated with and without PCC. Results: INR values on admission were above 2.0 in 37 patients, of whom 19 were given PCC (PCC group) and 18 were not given PCC (control group). In these 37 patients, the frequency of HE (p = 0.017), the number of patients with a poor clinical outcome (modified Rankin Scale score ≧3 at 30 days or at discharge; p = 0.045) and in-hospital mortality (p = 0.042) were significantly higher in the control than in the PCC group. On multivariate logistic regression analysis with adjustment, PCC administration was independently associated (odds ratio 0.03, 95% confidence interval 0.00–0.63; p = 0.023) with a reduction in poor clinical outcome in ICH patients whose INR values were >2.0 on admission. Conclusions: Immediate INR reversal with PCC may prevent HE and subsequent poor outcome.

Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study

BackgroundVascular endothelial growth factor (VEGF) is a well-known molecule mediating neuronal survival and angiogenesis. However, its clinical significance in ischemic stroke is still controversial. The goal of this study was to examine the temporal profile of plasma VEGF value and its clinical significance in ischemic stroke with taking its subtypes into consideration.MethodsWe prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy subjects. The stroke patients were divided into 4 subtypes: atherothrombotic infarction (ATBI, n = 34), lacunar infarction (LAC, n = 45), cardioembolic infarction (CE, n = 49) and other types (OT, n = 43). Plasma VEGF values were measured as a part of multiplex immunoassay (Human MAP v1.6) and we obtained clinical information at 5 time points (days 0, 3, 7, 14 and 90) after the stroke onset.ResultsPlasma VEGF values were significantly higher in all stroke subtypes but OT than those in the controls throughout 90 days after stroke onset. There was no significant difference in the average VEGF values among ATBI, LAC, and CE. VEGF values were positively associated with neurological severity in CE patients, while a negative association was found in ATBI patients. After adjustment for possible confounding factors, plasma VEGF value was an independent predictor of poor functional outcome in CE patients.ConclusionsAlthough plasma VEGF value increases immediately after the stroke onset equally in all stroke subtypes, its significance in functional outcome may be different among the stroke subtypes.

High Blood Pressure After Acute Ischemic Stroke Is Associated With Poor Clinical Outcomes Fukuoka Stroke Registry

The relationship between the poststroke blood pressure (BP) and functional outcomes in patients with acute ischemic stroke is still controversial. The aim of the present study was to elucidate the impact of the poststroke BP on the clinical outcomes of acute ischemic stroke. Among the patients in the Fukuoka Stroke Registry, 1874 patients with first-ever acute ischemic stroke (within 24 hours of onset) who had been functionally independent before onset were prospectively enrolled in the present study. The poststroke BP levels were defined as the average values during the 48 hours after onset. The study outcomes were a good neurological recovery, neurological deterioration, and a poor functional outcome. The higher poststroke BP levels were significantly associated with a lower probability of a good neurological recovery and elevated risks of neurological deterioration and a poor functional outcome after adjusting for potential confounding factors. The multivariate-adjusted odds ratios (95% confidence interval) in the highest quintile of systolic BP (versus the lowest quintile as a reference) were 0.51 (0.37–0.71) for a good neurological recovery, 1.92 (1.15–3.27) for neurological deterioration, and 2.51 (1.69–3.74) for a poor functional outcome. Similar associations were observed when we applied the poststroke diastolic BP or pulse pressure. No evidence of the J-curve phenomenon was observed for each association. These results suggest that a high poststroke BP was significantly associated with unfavorable clinical outcomes in patients with acute ischemic stroke. There was no evidence of the J-curve phenomenon between the poststroke BP levels and the clinical outcomes.

Risk factors predisposing to stroke recurrence within one year of non-cardioembolic stroke onset: the Fukuoka Stroke Registry.

Background: Recurrent strokes occur more frequently during the first year after an ischemic stroke. We investigated the relationship between patient clinical characteristics and stroke recurrence according to the non-cardioembolic type of ischemic stroke, and determined the predisposing factors associated with a recurrence within the first year. Methods: From June 2007 to December 2008, 1,106 consecutive ischemic stroke patients who were hospitalized in the 7 FSR stroke centers within 7 days after the onset of their stroke were enrolled in this study. We assessed the clinical characteristics of the patients on admission, and followed their clinical courses for one year. Results: Of all patients, 876 (537 males and 339 females, 70 ± 12 years of age) who had suffered from a non-cardioembolic stroke were investigated. Seventy-one patients (8.1%) suffered from a recurrence of ischemic stroke during the follow-up period of one year. On multivariate Cox hazard regression analyses, age (HR 1.03, 95% CI 1.00–1.05, p = 0.030, per 1-year increase), high-density lipoprotein (HDL) cholesterol <40 mg/dl (HR 1.89, 95% CI 1.10–3.24, p = 0.021), and chronic kidney disease (CKD) (HR 1.73, 95% CI 1.03–2.90, p = 0.038) were independent predictors of a recurrence within one year after the non-cardioembolic stroke. Conclusions: In the patients demonstrating non-cardioembolic ischemic stroke, low HDL cholesterol levels and CKD in addition to aging were independent risk factors for a recurrence within one year after the onset.

The impact of hyperacute blood pressure lowering on the early clinical outcome following intracerebral hemorrhage.

Objective Blood pressure lowering in acute intracerebral hemorrhage patients may prevent hematoma growth and neurological deterioration. The optimal goal of hyperacute antihypertensive therapy for intracerebral hemorrhage patients to obtain a favorable early clinical outcome was investigated. Methods Of 688 consecutive patients who were admitted to our stroke care units within 24 h after intracerebral hemorrhage onset, 244 patients who emergently received intravenous antihypertensive therapy due to admission blood pressure at least 180/105 mmHg were assessed. The average systolic and diastolic blood pressure values 6, 12, and 24 h after admission and the percentage reduction of the blood pressure value with respect to the admission blood pressure value were used for analysis. Results At 3 weeks, 66 patients (27%) had a completely independent activity level corresponding to a modified Rankin Scale score of 1 or less. After adjustment for baseline characteristics, a favorable functional outcome was more common in patients with the lowest quartile of average systolic blood pressure in the initial 24 h (<138 mmHg, odds ratio 4.36, 95% confidence interval 1.10–17.22), and was similarly common in those with the middle two quartiles (138–148 mmHg, 148–158 mmHg) than in those with the highest quartile of systolic blood pressure (≥158 mmHg). Analyses using patient quartiles on the basis of the average diastolic blood pressure or the reduction of systolic or diastolic blood pressure did not show an association with early outcome. Conclusion Lowering the systolic blood pressure to less than 138 mmHg during the initial 24 h appears to be predictive of favorable early outcome in intracerebral hemorrhage patients. Randomized controlled trials to answer this question are needed.

Significance of plasma adiponectin for diagnosis, neurological severity and functional outcome in ischemic stroke — Research for Biomarkers in Ischemic Stroke (REBIOS)

OBJECTIVE Although adiponectin is a major adipocytokine that affects the pathogenesis of various cardiovascular diseases, its clinical significance in stroke remains controversial. We investigated the clinical significance of plasma adiponectin for the diagnosis, neurological severity and functional outcomes of patients with ischemic stroke. METHODS We prospectively enrolled 171 patients with ischemic stroke and 171 age- and sex-matched healthy controls. Blood samples and clinical information were obtained at day 0, 3, 7, 14 and 90 after stroke onset. RESULTS Average adiponectin values at day 0 did not significantly differ between the controls and the patients, but were significantly lower and higher in patients with atherothrombotic brain (ATBI) (p=0.047) and cardioembolic (CE) (p=0.008) infarction, respectively, than in the controls. Multivariate logistic regression analyses showed that the adiponectin value at day 0 could predict ATBI (odds ratio, 0.75; 95% confidence interval, 0.58 to 0.91, p=0.009, per 1-μg/mL increase). Adiponectin values at day 0 were positively associated with neurological severity as evaluated by the National Institute of Health Stroke Scale upon admission (r=0.420, p=0.003) and were higher in the groups with poor outcomes (modified Rankin Scale (mRS) ≥ 3 on day 90) than in those with good ones (mRS ≤ 2) in all stroke subtypes, with statistical significance in ATBI (p=0.015). CONCLUSIONS Plasma adiponectin values may help to classify stroke subtypes and predict neurological severity and functional outcome in ischemic stroke patients.

Enlargement of Acute Intracerebral Hematomas in Patients on Long-Term Warfarin Treatment

Background: The relationship between warfarin administration and the frequent development of enlarged hematomas in patients with acute intracerebral hemorrhage (ICH) is controversial. The present study was carried out to examine this issue. Methods: This study reviewed 41 patients with nontraumatic ICH within 24 h after stroke onset from 1999 to 2003 who received long-term warfarin treatment (29 men and 12 women, 70 ± 12 years old) and 323 patients who had not been on warfarin (177 men and 146 women, 66 ± 13 years old). The hematoma volume (HV) on admission, final HV, frequency of hematoma enlargement (HE) and other background characteristics were investigated. Results: Both the HV on admission (p = 0.031) and final HV (p = 0.001) were larger in patients on warfarin than in those not receiving warfarin. HE occurred more frequently (p < 0.001), and mortality at 30 days or at discharge was higher (p = 0.003) in the warfarin group than in the control group. A multivariate adjusted logistic regression analysis showed that warfarin treatment (OR = 5.75, 95% CI = 2.41–13.8, p < 0.001), liver disease (OR = 2.59, 95% CI = 1.12–5.99, p = 0.026), and the National Institutes of Health Stroke Scale score (OR = 1.10, 95% CI = 1.04–1.15, p < 0.001, per 1-score increase) on admission were independently related to HE. Conclusions: Acute ICH in patients on long-term warfarin treatment appears to be associated with HE.

Intensity of Anticoagulation and Clinical Outcomes in Acute Cardioembolic Stroke The Fukuoka Stroke Registry

Background and Purpose— The relationship between the intensity of anticoagulation at the onset of acute cardioembolic stroke and clinical outcome after stroke is unclear. Here, we elucidated the relationship between prothrombin time–international normalized ratio (PT-INR) values on admission and clinical outcomes in patients with acute cardioembolic stroke. Methods— A total of 602 patients from the Fukuoka Stroke Registry in Japan who had been treated with warfarin but developed cardioembolic stroke were enrolled. The patients were classified into 3 groups according to their PT-INR values on admission: PT-INR <1.50, 411 patients; PT-INR 1.50 to 1.99, 146 patients; and PT-INR ≥2.00, 45 patients. The associations between PT-INR categories and severe neurological deficits (National Institutes of Health Stroke Scale ≥10) on admission and poor functional outcome (modified Rankin scale 4–6) at discharge were investigated using a logistic regression analysis. Results— Neurological deficits on admission were less severe, and functional outcome at discharge was more favorable as the PT-INR level on admission increased. The multivariate analysis revealed that severe neurological deficits were inversely associated with PT-INR on admission (PT-INR 1.50–1.99: odds ratio, 0.66; 95% confidence interval, 0.43–1.00; PT-INR ≥2.00: odds ratio, 0.41; 95% confidence interval, 0.20–0.83; compared with a reference group of PT-INR <1.50). Poor functional outcome was less likely in patients with PT-INR ≥2.00 (odds ratio, 0.20; 95% confidence interval, 0.06–0.55) after adjustment for confounders. Conclusions— Prestroke PT-INR ≥2.0 is associated with favorable clinical outcomes after acute cardioembolic stroke.