Pre-stroke habitual prolonged sleep as a predictor for post-stroke sleep quality, stroke-related quality of life, and lifestyle values.

BACKGROUND: Prolonged sleep is a higher stroke risk, but post-stroke prolonged sleep facilitates stroke recovery. No study has explored the relationship between pre- and post-stroke prolonged sleep and their involvement in stroke-related quality of life (QOL).This study aimed to clarify the role of pre- and post-stroke prolonged sleep in QOL and sleep quality during hospitalization. METHODS: Fifty-one subacute stroke inpatients were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Sleep quality and lifestyle values were assessed by original questionnaires. RESULTS: Patients in pre-stroke prolonged sleep > 8 h had a higher incidence of post-stroke poor sleep quality than those belonging to the normal or shorter hours (OR 5.33, 95% CI 1.30-21.84, p = 0.047). In addition, pre-stroke prolonged sleep was associated with lower scores of psychosocial QOL and lifestyle values of "accepting disability; caring about what other people think of what you do". In contrast, post-stroke prolonged sleep was associated with the lower risk of post-stroke poor sleep quality (OR 0.27, 95% CI 0.08-0.86, p = 0.045). Post-stroke high sleep quality had higher (better) scores of physical and energy QOL, and lifestyle values of "caring about what other people think of what you do; having some places to go out after discharge" compared with post-stroke poor sleep quality. Post-stroke prolonged sleep was derived from pre-stroke not prolonged sleep rather than pre-stroke prolonged sleep (p = 0.039, Chi-square test). CONCLUSIONS: Pre-stroke prolonged sleep is associated with a higher incidence of post-stroke poor sleep quality and lower scores of QOL and lifestyle values after stroke.

Persistent or permanent atrial fibrillation is associated with severe cardioembolic stroke in patients with non-valvular atrial fibrillation.

BACKGROUND: Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke severity in patients with CE stroke divided by the type of AF. METHODS: Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between patients with PAF (n = 127) and PerAF (n = 231). RESULTS: Patients with PerAF were more likely to take oral anticoagulants (OACs) than those with PAF (37% vs. 13%, P <  0.0001), even though still underuse of OAC in both patients. Regarding stroke severity on admission, patients with PerAF exhibited a tendency toward a higher score on the National Institutes of Health Stroke Scale (NIHSS) compared with patients with PAF (12 [5-20] vs. 9 [4-18]; P = 0.12). Mortality and mRS score at discharge were higher in the PerAF than in the PAF group (13% vs. 4%; P = 0.005, and 3 [1-5] vs. 2 [1-4]; P = 0.01, respectively). Multivariate analyses confirmed that PerAF was a significant determinant of severe stroke (NIHSS score > 8) on admission (odds ratio [OR] to PAF = 1.80; 95% confidence interval [CI] 1.08-2.98; P = 0.02) and of an mRS score ≥ 3 at discharge (OR = 2.07; 95% CI 1.24-3.46; P = 0.006). Patients with PerAF had three times more internal carotid artery occlusion evaluated by magnetic resonance angiography, which indicated a more severe cerebral embolism compared with patients with PAF. CONCLUSIONS: We found underuse of OAC in high risk AF patients with CE stroke. PerAF is significantly associated with severe stroke on admission and an unfavorable functional outcome at discharge in Japanese patients with CE stroke.

Incidence and characteristics of spontaneous platelet macro-aggregation in acute ischemic stroke.

Spontaneous platelet aggregation is a trigger for additional development of larger thrombi. Micro-aggregation is observed in 10% of diabetes approximately and blocked by P2Y12 inhibitors, whereas macro-aggregation is associated with overexpression of platelet α2-adrenoreceptors and is not blocked by conventional anti-platelet medicines. We examined the incidence of spontaneous platelet macro-aggregation (SPMA) in acute ischemic stroke and analyzed its clinical characteristics. Out of 665 consecutive acute ischemic strokes, SPMA was found in 10 patients (1.5%, one tenth of micro-aggregation) despite no detection in 588 control subjects. Types of ischemic stroke were 4 atherothrombotic, 4 cardioembolic, and 2 lacunar strokes. Stroke with SPMA exhibited higher (worse) values of modified Rankin Scales (mRS) at discharge (3.00 ± 0.53 vs 1.93 ± 0.07, p = 0.042 by Wilcoxon) compared with stroke without SPMA despite no difference at admission. The proportion of patients who were functionally independent (score 0-2 on the mRS) at discharge was lower in stroke with SPMA compared with stroke without SPMA (p < 0.05 by chi-square test; OR 3.60, 95% CI 1.08-12.03; RR 2.04, 95% CI 1.05-2.86). It was intriguing that severe (high magnitude) SPMA was observed in 4 atherothrombotic stroke. Although anti-platelet therapy underwent, the proportion of atherothrombotic patients who were functionally improved and independent at discharge was lower in the presence of SPMA compared with the absence of SPMA (p < 0.05 by chi-square test). The patients with SPMA were more likely to be older, having major disabilities, being less functionally improved during hospitalization, and being less functionally independent at discharge.

D-dimer and C-reactive Protein as Potential Biomarkers for Diagnosis of Trousseau's Syndrome in Patients with Cerebral Embolism.

BACKGROUND: Differentiating stroke due to Trousseau's syndrome from other types of cerebral embolism is challenging, especially in patients with occult cancer. The current study aimed to determine predicting factors and biomarkers of stroke due to Trousseau's syndrome. METHODS: This retrospective study comprised 496 consecutive patients with acute cerebral embolism, including 19, 85, 310, and, 82 patients with stroke due to Trousseau's syndrome, artery-to-artery embolism, cardioembolic stroke, and embolic stroke with undetermined source, respectively. All patients were evaluated within 72 hours of onset. The clinical characteristics, laboratory findings, and patterns on diffusion-weighted magnetic resonance imaging (DWI) were compared among the groups. RESULTS: Plasma D-dimer and C-reactive protein (CRP) levels were significantly higher in the Trousseau's syndrome than in the other causes of cerebral embolism. Multivariate analyses demonstrated that female sex, multiple lesions on DWI, high D-dimer and CRP levels, and low platelet and low brain natriuretic peptide levels were independent predictors that could distinguish Trousseau's syndrome from the other causes of cerebral embolism. The cutoff values of D-dimer and CRP to identify stroke due to Trousseau's syndrome was 2.68 µg/mL fibrinogen equivalent units and .29 mg/dL, respectively. CONCLUSIONS: The elevated D-dimer and CRP levels on admission in addition to specific clinical features may be useful for diagnosis of Trousseau's syndrome in patients with cerebral embolism.

Collagen-Induced Platelet Aggregates, Diabetes, and Aspirin Therapy Predict Clinical Outcomes in Acute Ischemic Stroke.

BACKGROUND: Aggregation of platelets is a trigger for additional development of larger thrombi. This study aimed to identify factors that may affect platelet aggregability and their role in clinical outcomes in acute ischemic stroke. METHODS: Consecutive acute ischemic stroke patients (n = 352) who were transferred within 24 hours after its onset were enrolled. Peripheral venous blood was sampled to measure platelet aggregability and other parameters. RESULTS: Mean values of spontaneous small-sized platelet aggregates and collagen- or adenosine diphosphate (ADP)-induced large-sized aggregates were elevated in acute ischemic stroke. In atherothrombotic stroke (n = 178), collagen and ADP-induced large-sized aggregates were positively correlated with HbA1c, respectively. High incidence of the modified Rankin Scales (mRS) 5-6 at discharge was associated with diabetes complication (odds ratio [OR] 8.77, 95% confidence interval [CI] 1.32-57.56). The proportion of patients who were functionally independent (the mRS 0-2) at discharge was lower in the middle tertile of collagen and ADP-induced large-sized aggregates than their low tertile (OR 2.46, 95% CI 1.09-5.58; OR 2.43, 95% CI 1.05-5.59, respectively). Prestroke administration of aspirin recovered the proportion of independence at discharge (OR 0.25, 95% CI 0.06-0.99), and ameliorated incidence of the mRS 5-6. On logistic regression analysis, diabetes, HbA1c, collagen-induced large-sized aggregates, and prestroke administration of aspirin remained independent predictors of clinical outcomes in atherothrombotic stroke. In cardioembolic and lacunar stroke, no relations with clinical outcomes were found. CONCLUSIONS: High plasma level of HbA1c is involved in enhanced platelet aggregability in acute atherothrombotic stroke patients, and prestroke administration of aspirin may be beneficial to clinical outcomes.

Factors Influencing Quality of Life in Stroke Patients: Focus on Eating Habits.

BACKGROUND: Adherence to healthy lifestyle factors has been shown to improve outcomes after stroke. This study aimed to identify lifestyle factors about eating habits that may affect the quality of life (QOL) in elderly stroke patients. METHODS: Fifty elderly patients with a first-ever stroke were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Lifestyle factors about eating habits were collected using questionnaires (Questions 1-17) for the intake of salt, calcium, magnesium, potassium, taurine, fiber, and protein, and the frequency of breakfast. RESULTS: QOL of physical, communication, and psychosocial subdomains was better in the low (healthy) tertile of poststroke eating habits (Questions 1-17) compared with the high tertile of post-troke eating habits (Questions 1-17). This relationship appeared in eating habits except for salt intake but not in eating habits of salt intake and directly measured salt intake. Compared with prestroke eating habits score, poststroke eating habits score was decreased (improved) in 36 patients concerning eating habits of salt intake, but only in 12 patients concerning eating habits except for salt intake (P < .05 by chi-square test). Poststroke eating habits of calcium and magnesium were associated with better psychosocial QOL and better physical or energy QOL, respectively. CONCLUSIONS: Poststroke eating habits of calcium and magnesium were associated with QOL in elderly patients with a first-ever stroke. Since eating habits except for salt intake was poorly improved after stroke, intensive interventions regarding eating habits might be important.

Low Body Mass Index is a Poor Prognosis Factor in Cardioembolic Stroke Patients with NonValvular Atrial Fibrillation.

BACKGROUND: The relationship between body mass index (BMI) and the severity of cardioembolic stroke (CES) remains poorly understood. METHOD: A total of 419 consecutive CES patients with nonvalvular atrial fibrillation (NVAF), and with a modified Rankin Scale (mRS) score of 0 or 1 before onset admitted within 48hours after onset to the Hirosaki Stroke and Rehabilitation Center were studied. The patients were divided into three groups, low BMI (L-BMI; n = 36, BMI < 18.5 kg/m2), normal BMI (N-BMI; n = 284, 18.5 ≤ BMI < 25.0), and high BMI (H-BMI; n = 99, BMI ≥ 25.0). We compared stroke severity and functional outcome among the three groups. RESULTS: Stroke severity on admission, assessed by the National Institutes of Health Stroke Scale (NIHSS) showed that patients with L-BMI had the highest NIHSS score (median, 16 [11-25]), followed by N-BMI and H-BMI (11 [5-19] and 9 [3-19], P = .002). Functional outcome at discharge, assessed by mRS, was most severe in L-BMI patients (5 [3-5]), followed by N-BMI and H-BMI (3 [1-4] and 2 [1-4], P = .001). Multivariate analyses revealed that L-BMI was a significant determinant of severe stroke (NIHSS scores ≥8) at admission (odds ratio [OR] to N-BMI = 2.79, 95% confidence interval [CI], 1.17-7.78, P = .02) and poor functional outcome (mRS scores ≥3) at discharge (OR = 2.53, 95% CI, 1.12-6.31, P = .02). However, H-BMI did not affect stroke severity at admission or functional outcome at discharge. CONCLUSION: Low BMI is a risk factor for severe stroke on admission and unfavorable functional outcome at discharge in Japanese CES patients with NVAF.

Spontaneous Micro-Aggregation of Platelets Predicts Clinical Outcome in Acute Ischemic Stroke.

BACKGROUNDS: Spontaneous micro-aggregation of platelets (SMAP) is frequently observed in stroke patients and is a trigger for the additional development of larger thrombi. We tested the hypothesis that SMAP may predict clinical outcome in acute ischemic stroke patients. METHODS AND RESULTS: Consecutive acute ischemic stroke patients (n = 358) who were transferred to our hospital within 24 hours after its onset were enrolled. Peripheral venous blood was sampled to measure various parameters when they arrived. SMAP was correlated with plasma brain natriuretic peptide and diastolic blood pressure positively, and with serum albumin and body weight negatively. Multivariable Cox regression analysis showed that only serum albumin was an independent predictor of the SMAP (P = .0023). The proportion of patients who were functionally independent (score 0-2 on the modified Rankin Scales) at discharge was lower in the third tertile of SMAP (higher level) as compared with the first and the second tertiles in ischemic stroke (odds ratio [OR], 5.76; 95 % confidence interval [CI], 3.31-10.05; P < .0001) and atherothrombotic stroke (P = .02 by chi-square test). The lower proportion of patients achieving independence was found in the first tertile of serum albumin (lower level) as compared with the second and third tertiles in ischemic (OR, 4.60; 95% CI, 2.66-7.95; P < .0001), atherothrombotic, and cardioembolic stroke (P = .004 and P < .0001 by chi-square test). On logistic regression analysis, SMAP and serum albumin remained independent predictors of poor outcome in ischemic stroke. CONCLUSIONS: SMAP within 24 hours after stroke onset is a novel independent predictor of clinical outcome in acute ischemic stroke patients.

Impact of Atrial Natriuretic Peptide Value for Predicting Paroxysmal Atrial Fibrillation in Ischemic Stroke Patients.

INTRODUCTION: The impact of atrial natriuretic peptide (ANP) value for predicting paroxysmal atrial fibrillation (pAF) in ischemic stroke patients remains uncertain. METHODS: The consecutive 222 ischemic stroke patients (median 77 [IQR 68-83] years old, 93 females) within 48 hours after onset were retrospectively studied. Plasma ANP and brain natriuretic peptide (BNP) levels were simultaneously measured at admission. Of all, 158 patients had no evidence of atrial fibrillation (AF) (sinus rhythm [SR] group), 25 patients had pAF (pAF group), and the other 39 patients had chronic AF (cAF group). We investigated predicting factors for pAF, with focus on ANP, BNP, and ANP/BNP ratio. RESULTS: ANP value was significantly higher in the pAF than in the SR group (97 [50-157] mg/dL versus 42 [26-72] mg/dL, P < .05) and further increased in the cAF group (228 [120-392], P < .05 versus pAF and SR groups). Similarly, the BNP value was higher in the pAF than in the SR group (116 [70-238] mg/dL versus 34 [14-72] mg/dL, P < .05) and further increased in the cAF group (269 [199-423], P < .05 versus pAF and SR groups). ANP/BNP ratio was lower in the pAF and cAF groups than in the SR group (.6 [.5-1.2] and .7 [.5-1.0] versus 1.3 [.8-2.4], both P < .05]. Multivariate analysis in the SR and pAF groups (n = 183) demonstrated that age, congestive heart failure, ANP, and BNP, but not ANP/BNP ratio, were independent predictors for detecting pAF. Receiver operating characteristic curve analysis further showed that area under the curve was similar between ANP and BNP (.76 and .80). CONCLUSIONS: ANPmay be clinically useful for detecting pAF in ischemic stroke patients as well as BNP.

Effect of rivaroxaban on prothrombin fragment 1+2 compared with warfarin in patients with acute cardioembolic stroke: Insight from its serial measurement.

INTRODUCTION: Patients with intracerebral hemorrhage during rivaroxaban treatment have small hematoma and favorable outcomes compared with those with warfarin. We investigated its possible mechanism, focusing on prothrombin fragment 1+2 (F1+2), a marker of thrombin generation. MATERIALS AND METHODS: In 65 patients with acute cardioembolic stroke (median 77years), rivaroxaban was initiated at 5days after the onset. Plasma F1+2 level (normal range, 69-229pmol/L), prothrombin time (PT), and rivaroxaban concentration evaluated by anti-Xa activity were serially measured. RESULTS: Median plasma F1+2 was 276 (IQR, 195-454) pmol/L before starting rivaroxaban, and significantly decreased to 196 (141-267) and 192 (151-248) on 7 and 28days after rivaroxaban, respectively (both p<0.05). Serial measurements of PT and rivaroxaban concentration at trough, 2, 4, and 6h after taking rivaroxaban showed a positive correlation (R2=0.69, p<0.01). PT at 4h after rivaroxaban was significantly prolonged compared with trough (16.6 versus 11.5s, p<0.0001). F1+2 at 4h was also decreased compared with trough (160 (123-245.5) versus 196 (141-266.5), p=0.04), but no patients showed F1+2 below the normal range at 4h. In other 34 patients with warfarin treatment (77years), median PT-INR and F1+2 were 2.06 (1.75-2.50) and 75 (48-111) (p<0.0001 versus 4h after rivaroxaban). Notably, of those with PT-INR≥2.0 (18/34), 12 (12/18, 67%) showed F1+2 below the normal range. CONCLUSIONS: Rivaroxaban retains a normal thrombin generation even at its peak level with prolonged PT, whereas warfarin at therapeutic levels inhibits thrombin generation. This may partly explain different outcomes in patients complicated with bleeding events.

Quality of Life in Physical and Psychological Health and Social Environment at Posthospitalization Period in Patients with Stroke.

BACKGROUND: Interaction of quality of life (QOL) in physical and psychological health and social environment has not been tested in stroke during a posthospitalization period, and a better understanding of the components of QOL would lead to a more integrated and person-centered approach to health management and outcome optimization. We investigated how QOL emerges from the sequelae of stroke and interacts with each other during the posthospitalization period. METHODS: We performed a cross-sectional study in 53 outpatients of stroke survivors (39 men and 14 women with a mean age of 66 years, 46 infarctions, and 7 hemorrhages). RESULTS: Eight QOL domains of psychological health were scored by interview, and 2 of them ("desire to distend what they can do" or "desire to do rehabilitation") were associated with the improvement of physical health during the posthospitalization period (P < .05 and P = .08, respectively). These patients were characterized by the items like "I need to succeed for health improvement, to go home, to go back to work, and to see grandchildren" as goals to achieve their desire (P < .05). In interaction of QOL in psychological health and social environment, another psychological domain "to gain satisfaction from the experience" was closely related to the presence of hobby or work before stroke attack (P < .05). CONCLUSION: During the posthospitalization period, QOL of psychological health may support that of physical health, being associated with the presence of hobby or work before stroke attack.

Prothrombin time on admission in patients with cardioembolic stroke and intracranial hemorrhage occurring during warfarin treatment in the direct oral anticoagulant era.

Warfarin is used worldwide to prevent cardioembolic stroke (CES) in patients with atrial fibrillation even in the era of direct oral anticoagulant (DOAC). We evaluated clinical characteristics of the patients with CES and intracerebral hemorrhage (ICH) occurring during warfarin treatment, focusing on prothrombin time-international normalized ratio (PT-INR) at the occurrence. The consecutive 846 CES patients (78 ± 9 years) and 870 ICH patients (68 ± 13 years) admitted to the Hirosaki Stroke and Rehabilitation Center from April 2011 through March 2015 were studied. The antithrombotic agents administered in CES patients before the onset included antiplatelets in 146 patients (17%), warfarin in 205 (24%), DOAC in 37 (5%), and none in the other 458 (54%). Mean PT-INR within 24 hours after the onset in nonvalvular atrial fibrillation patients with warfarin was 1.34 ± 0.33 (n = 129), and 111 of them (86%) showed PT-INR value below the recommended therapeutic range in Japan. The antithrombotic agents administered in ICH patient included antiplatelets in 87 patients (10%), warfarin in 86 (10%), DOAC in 8 (1%), and none in the other 689 (79%). Mean PT-INR within 24 hours after the onset in patients with warfarin was 2.27 ± 0.62 (n = 65), and 56 of them (86%) showed PT-INR < 2.8. Thus, there is a large population with poor warfarin control complicating CES and that with good warfarin control complicating ICH, indicating limitation of warfarin treatment in the DOAC era.

Relationship between the lesion location of acute ischemic stroke and early depressive symptoms in Japanese patients.

BACKGROUND: Approximately one-third of stroke survivors suffer from post-stroke depression (PSD) in the acute or chronic stages. The presence of PSD in the acute stage after stroke is reportedly associated with poor patient prognosis; therefore, early recognition and treatment of PSD may alleviate these consequences. The aim of the current study was to examine the relationship between the lesion location and the presence of early depressive symptoms after acute ischemic stroke in Japanese patients. METHODS: Our study included 421 patients who suffered from acute ischemic stroke. On the day of admission, the lesion location was determined using magnetic resonance imaging (MRI). Stroke severity was measured on the seventh day of hospitalization withat the National Institutes of Health Stroke Scale (NIHSS). On the tenth day of hospitalization, depressive symptoms were measured and functional assessments were performed with the Japan Stroke Scale (Depression Scale) (JSS-D) and functional independence measure (FIM), respectively. RESULTS: A total of 71 subjects (16.9 %) were diagnosed with depression. According to the multiple logistic regression analysis, the infarcts located at frontal and temporal lobes were found to be a significant independent risk factor of early depressive symptoms in the acute stage of stroke. CONCLUSIONS: Patients suffering from acute ischemic stroke, particularly in the frontal and temporal lobes, should be carefully assessed to detect and treat early depressive symptoms; such treatment may improve patient outcomes.

Effect of depressive symptoms on the length of hospital stay among patients hospitalized for acute stroke in Japan.

BACKGROUND: Depression after stroke is one of the most serious complications of stroke. Although many studies have shown that the length of hospital stay (LOHS) is a measurable and important stroke outcome, research has found limited evidence concerning the effect of depression on LOHS among patients who have experienced acute stroke. The objective of this study was to assess the effect of depression on LOHS among patients hospitalized for acute ischemic stroke in Japan. METHODS: We retrospectively examined 421 patients who had experienced acute ischemic stroke. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS) on the 7th day of hospitalization. On the 10th day of hospitalization, depressive symptoms and functional assessment were assessed by the Japan Stroke Scale (Depression Scale) and the Functional Independence Measure, respectively. A general linear model was employed to assess the effect of probable depression on LOHS. RESULTS: The prevalence of probable depression in the current sample was 16.3% in males and 17.8% in females. The mean LOHS of participants with probable depression (76.4±49.2 days) was significantly longer than that of participants without probable depression (44.9±39.2 days). An analysis using the general linear model to assess the effect on LOHS revealed a significant interaction between the presence of probable depression and NIHSS scores. CONCLUSION: Depression after stroke was associated with significant increases in LOHS. Early detection and treatment for depression are necessary for patients with ischemic stroke.

Impact of Sex Difference on Severity and Functional Outcome in Patients with Cardioembolic Stroke.

INTRODUCTION: Female sex is a risk factor for thromboembolic events in Caucasian, but not in Japanese, patients with nonvalvular atrial fibrillation. However, it remains unclear whether the female sex is also a risk factor for severe stroke and unfavorable functional outcome in patients with cardioembolic (CE) stroke. METHODS: Three hundred fifty-five consecutive patients with CE stroke within 48 hours after onset and with a modified Rankin Scale (mRS) score of 1 or lower before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between female (n = 157) and male (n = 198) patients. RESULTS: The mean age was higher in female than in male patients (80 ± 8 versus 75 ± 9 years, P < .00001). The congestive heart failure, hypertension, age [≥ 75 years], diabetes, stroke/transient ischemic attack [TIA] (CHADS2) score before onset was similar between the two groups (median, 3 [2-4] in both groups). Stroke severity on admission, assessed by the National Institutes of Health Stroke Scale (NIHSS), was higher in female than in male patients (13 [5-20] versus 8 [3-16], P = .0009). Functional outcome at discharge, assessed by mRS, was unfavorable in female than in male patients (3 [1-5] versus 2 [1-4], P = .005). An mRS score of 3 or higher at discharge was found more in female than in male patients (59% versus 39%, P = .0001). Multivariate analyses confirmed that female sex was a significant determinant of severe stroke (NIHSS ≥ 8) on admission (odds ratio [OR] to male = 1.97; 95% confidence interval [CI]; 1.24-3.15, P = .004) and for the mRS score of 3 or higher at discharge (OR = 1.83; 95% CI, 1.16-2.89; P = .01). Similar results were obtained by propensity-score matching analysis. CONCLUSIONS: Female sex is a risk factor for severe stroke on admission and unfavorable functional outcome at discharge in Japanese patients with CE stroke.

Severity and Functional Outcome of Patients with Cardioembolic Stroke Occurring during Non-vitamin K Antagonist Oral Anticoagulant Treatment.

BACKGROUND: Severity and functional outcome of patients with cardioembolic stroke (CE) occurring during non-vitamin K antagonist oral anticoagulant (NOAC) treatment remain uncertain. METHODS: The consecutive 355 CE patients within 48 hours after onset and with modified Rankin Scale (mRS) score of 1 or less before onset were studied. Of all, 262 patients were treated with no anticoagulants (non-AC), 63 with warfarin below therapeutic range of prothrombin time-international normalized ratio (PT-INR) on admission (PT-INR <1.6 [WF-Lo]), 16 with warfarin within therapeutic range (PT-INR ≥1.6 [WF-Tp]), and 14 with NOACs (9 dabigatran and 5 rivaroxaban [NOAC-DR]). We compared severity and functional outcome of CE patients among these 4 groups, especially focusing on patients during NOAC treatment. RESULTS: Stroke severity on admission, assessed by the National Institutes of Health Stroke Scale, was lower in WF-Tp (median, 5 [1-15]) and NOAC-DR (5 [3-6]) than in non-AC (11 [5-19]) and WF-Lo (12 [5-19]; P = .006). Functional outcome at discharge, assessed by mRS, was favorable in WF-Tp (median, 1 [0-4]) and NOAC-DR (1 [1-2]) compared with that in non-AC (2 [1-4]) and WF-Lo (3 [1-5]; P = .02), and ratios of the patients with mRS score of 1 or less were 63% and 64% versus 31% and 33%, respectively (P = .005). Multivariate analysis also showed a favorable functional outcome at discharge in WF-Tp and NOAC-DR groups. Drug management was likely associated with NOAC-associated CE. CONCLUSIONS: Stroke severity and functional outcome of CE patients treated with warfarin within therapeutic range and with NOACs are similar to each other, and are more favorable than those with no anticoagulants and with warfarin below therapeutic range.

Characteristics of intracerebral hemorrhage during rivaroxaban treatment: comparison with those during warfarin.

BACKGROUND AND PURPOSE: Neuroradiological characteristics and functional outcomes of patients with intracerebral hemorrhage (ICH) during novel oral anticoagulant treatment were not well defined. We examined these in comparison with those during warfarin treatment. METHODS: The consecutive 585 patients with ICH admitted from April 2011 through October 2013 were retrospectively studied. Of all, 5 patients (1%) had ICH during rivaroxaban treatment, 56 (10%) during warfarin, and the other 524 (89%) during no anticoagulants. We focused on ICH during rivaroxaban and warfarin treatments and compared the clinical characteristics, neuroradiological findings, and functional outcomes. RESULTS: Patients in the rivaroxaban group were all at high risk for major bleeding with hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS-BLED) score of 3 and higher rate of past history of ICH. Moreover, multiple cerebral microbleeds (≥4) were detected more frequently in rivaroxaban group than in warfarin (80% versus 29%; P=0.04). Hematoma volume in rivaroxaban group was markedly smaller than that in warfarin (median: 4 versus 11 mL; P=0.03). No patient in the rivaroxaban group had expansion of hematoma and surgical treatment. Rivaroxaban group showed lower modified Rankin Scale at discharge relative to warfarin, and the difference between modified Rankin Scale before admission and at discharge was smaller in rivaroxaban than in warfarin (median: 1 versus 3; P=0.047). No patient in the rivaroxaban group died during hospitalization, whereas 10 (18%) warfarin patients died. CONCLUSIONS: Rivaroxaban-associated ICH occurs in patients at high risk for major bleeding. However, they had a relatively small hematoma, no expansion of hematoma, and favorable functional and vital outcomes compared with warfarin-associated ICH.

Reduced smoke-like echo and resolved thrombus in the left atrium with rivaroxaban therapy in an acute cardioembolic stroke patient.

We report a case of a nonvalvular atrial fibrillation (NVAF) patient with acute cardioembolic stroke in whom rivaroxaban, an oral direct factor Xa inhibitor, reduced a smoke-like echo in the left atrium and resolved a thrombus in the left atrial appendage. A 71-year-old man was admitted because of the sudden onset of right hemiplegia and aphasia and was diagnosed with acute cardioembolic stroke associated with NVAF. The patient had not been treated with warfarin before admission, and rivaroxaban therapy (15 mg once daily) was initiated. Transesophageal echocardiography was performed on day 8 and a mobile thrombus was found in the left atrial appendage, accompanied by a remarkable smoke-like echo in the left atrium. Notably, the thrombus was resolved and the smoke-like echo was reduced on day 40. No recurrent ischemic stroke occurred. We describe favorable effects of rivaroxaban on the reduction of a smoke-like echo and on the resolution of a thrombus in the left atrium in an NVAF patient with acute cardioembolic stroke.

Coupling factor 6 enhances the spontaneous microaggregation of platelets by decreasing cytosolic cAMP irrespective of antiplatelet therapy.

The spontaneous microaggregation of platelets (SMAPs) is a marker for the prognosis of patients with cardiovascular diseases. Coupling factor 6 (CF6) binds to the plasma membrane ATP synthase and functions as a pro-atherogenic molecule in the cardiovascular system. However, the role of CF6 in SMAPs and stroke remains unknown. In 650 consecutive patients, including those with acute-onset stroke, and 20 control subjects, platelet-rich plasma (PRP) was obtained, and SMAP was measured using a laser light-scattering aggregometer. The cytosolic cyclic adenosine monophosphate (cAMP) concentration in platelets was measured using an enzyme-linked immunosorbent assay. CF6 increased SMAPs in patients and control subjects to a similar degree by binding to the α- and ß-subunits of ATP synthase and inducing intracellular acidosis. It was abolished by PRP pretreatment with antibodies against CF6, and the α- or ß-subunit of the plasma membrane ATP synthase, and the ATP synthase inhibitor efrapeptin. CF6 increased SMAPs in patient groups with and without antiplatelet therapy to a similar degree, and no difference was found among the subgroups taking aspirin, thienopyridine or cilostazol. The cytosolic cAMP concentration in platelets was decreased by CF6 in the presence of the direct adenylate cyclase activator forskolin. Pretreatment of PRP with the Gs activator cholera toxin blocked the decrease, whereas the Gi inactivator pertussis toxin and cilostazol had no influence. The CF6-induced acceleration of SMAPs was suppressed by cholera toxin but not by cilostazol or pertussis toxin. CF6 enhanced SMAPs by decreasing cytosolic cAMP. Because it was observed irrespective of antiplatelet agents, CF6 appears to be a novel target for antiplatelet therapy.