The effects of combined early oral health care and early mobilisation on the incidence of stroke-associated pneumonia.

OBJECTIVE: To investigate the effects of combined early oral healthcare and early mobilisation on the incidence of stroke-associated pneumonia during hospitalisation of acute stroke patients. MATERIALS AND METHODS: In this single-centre, non-blinded, before-and-after cohort study, patients received basic stroke rehabilitation by a multidisciplinary team within 72 h of symptom onset from July to September 2016 and from July to September 2018. Patients were divided into two groups: 1) patients who received combined early oral healthcare and early mobilisation (early intervention group) (n=107), and 2) patients who received usual care (control group) (n=107). The relationship between the stroke-associated pneumonia incidence and prognosis was examined. RESULTS: The early intervention group had a significantly lower incidence of stroke-associated pneumonia than the control group (0.93% vs. 7.48%; P=0.01). Moreover, the early intervention group had a significantly lower proportion of patients who died or required medical care because of recurrent pneumonia at discharge (0.93% vs. 5.6%; P=0.04). In contrast, there were no significant differences between the two groups regarding the Revised Hasegawa's Dementia Scale on day 14 (22.5 vs. 23; P=0.87), Functional Independence Measure on day 14 (112 vs. 116; P=0.06), and rate of total oral diet (Food Intake LEVEL Scale ≥7) at discharge (95.2% vs. 93.5%; P=0.55). CONCLUSIONS: Combined early oral healthcare and early mobilisation by a multidisciplinary team significantly decreased the stroke-associated pneumonia incidence within 7 days and reduced the percentage of patients who died or required medical care because of recurrent pneumonia 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.

Clinical Outcomes and Medical Costs of Hydration Therapy with Hydroxyethyl Starch (130/0.4) or Acute Single Infarction.

OBJECTIVES: To investigate the effects of hydration with or without Hydroxyethyl Starch (HES) 130/0.4 on neurological outcomes and medical costs during hospitalisation in patients with a single infarction (SI) in the posterior lenticulostriate artery (LSA) territory. MATERIALS AND METHODS: In this retrospective, single-centre, non-blinded cohort study, SI in the posterior LSA was defined as an ischaemic lesion with a high-signal intensity area ≥20 mm. All patients received basic stroke care within 48 h of symptom onset between April 2015 and January 2019. Patients were divided into the following two groups by clinician's preference: 1) those administered HES 130/0.4 and 2) those receiving other infusion fluid. The relationships between hospital costs and hydration therapy type were examined. RESULTS: Eighteen (31%) of 58 patients received HES 130/0.4. The HES group had a significantly lower total cost than the control group (3.6 vs. 6.4 million yen, p=0.006). Moreover, the HES group had a significantly shorter hospital stay duration (79.5 vs. 141.0 days) and lower National Institutes of Health Stroke Scale score on day 7. Multivariate analysis found that HES 130/0.4 administration was an independent factor associated with high costs. CONCLUSIONS: Hydration therapy with HES 130/0.4 significantly decreased the total costs and hospitalisation duration of patients with SI in the posterior LSA territory.

Serum Albumin, Body Mass Index, and Preceding Xa and P2Y12 Inhibitors Predict Prognosis of Recurrent Ischemic Stroke.

BACKGROUND: A third to half of recurrent stroke occur while on antiplatelet therapy, but no study has explored factors relating to prognosis of recurrent ischemic stroke. This study aimed to clarify the risk factors to determine the clinical outcome of recurrent ischemic stroke. METHODS: A total of 1,333 consecutive acute ischemic stroke patients (first n = 492, recurrent n = 841) were enrolled. We explored factors influencing the modified Rankin Scales (mRS) at discharge that included platelet aggregability, preceding medicines, and well-known risks of biochemical data using Chi-square test or Fisher's exact probability test. RESULTS: As to preceding medicines, the proportion of patients who were functionally independent (mRS 0-2) at discharge was higher in preceding P2Y12 inhibitor that suppressed ADP- and collagen-induced macro-aggregation of platelet and Xa inhibitor or warfarin in cardioembolic stroke, but lower in P2Y12 inhibitor and Xa inhibitor or warfarin in lacunar stroke compared with no medicine. Regardless of LDL-cholesterol and HA1c, the mRS at discharge ≤ 2 was increased in the third tertile of serum albumin and body mass index (BMI) in atherothrombotic stroke; serum albumin and high-density lipoprotein cholesterol (HDL-C) in lacunar stroke; and serum albumin, HDL-C and BMI in cardioembolic stroke. Logistic regression analysis identified the following independent predictors for clinical outcome: serum albumin, HDL-C, BMI, and preceding Xa inhibitor and P2Y12 inhibitor. CONCLUSION: Regardless of well-known risk factors such as diabetes and high LDL-C, preceding treatment for Xa inhibitor or P2Y12 inhibitor, serum albumin, HDL-C, and BMI were associated with prognosis in recurrent ischemic stroke.

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.

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.

YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

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.

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.

Analysis of Factors Associated with Progression and Long-Term Outcomes of Penetrating Artery Territory Infarction: A Retrospective Study.

BACKGROUND: Patients with penetrating artery territory infarction occasionally show progressive motor deficits during the acute stage with poor prognosis. Predictive indices or medical therapies for suppressing the symptomatic progression (SP) of penetrating artery infarction have not been established. In this study, we investigated SP-related clinical factors and functional outcomes, specifically improvement 3 months post ictus in patients with penetrating artery infarction. METHODS: We retrospectively examined acute stroke patients with penetrating artery infarction admitted at 7 collaborative hospitals. SP was defined as an increase by 1 point or higher in the National Institutes of Health Stroke Scale score. Functional improvement was assessed based on the modified Rankin Scale at 3 months. The influence of factors, such as patient characteristics, clinical data, medical treatment during the acute stage and on SP, and functional improvement was statistically analyzed. RESULTS: Four hundred eighty-eight patients (310 men; mean age, 70 years) were examined. Sixty-eight patients (14%) exhibited SP. Multivariate logistic regression analysis revealed that higher hemoglobin A1c (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.10-1.55), body mass index (BMI; OR, .85; 95% CI, .77-.94), and systolic blood pressure on admission (OR, 1.63; 95% CI, 1.19-2.25) were independent predictors of SP in penetrating artery infarction. Dual antiplatelet therapy (DAPT; OR, 3.48; 95% CI, 1.52-8.38) independently influenced functional improvement. CONCLUSIONS: Initial high blood pressure, diabetes, and low BMI on admission were associated with early progression of penetrating artery infarction. DAPT during the acute stage may contribute to functional improvement.

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.

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.

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.

Atrial Fibrillation After Ischemic Stroke Detected by Chest Strap-Style 7-Day Holter Monitoring and the Risk Predictors: EDUCATE-ESUS.

AIM: This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708). METHODS: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors. RESULTS: The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). CONCLUSIONS: In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.

Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome.

The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in Japanese individuals with metabolic syndrome. The study population comprised 2150 Japanese individuals with metabolic syndrome, including 411 subjects with CKD [estimated glomerular filtration rate (eGFR) <50 mL/min/1.73m(2)] and 1739 controls (eGFR >/=60 mL/min/1.73m(2)). The genotypes for 100 polymorphisms of 80 candidate genes were determined. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that nine polymorphisms of APOE, ABCA1, PTGS1, TNF, CPB2, AGTR1, OR13G1, and GNB3 were associated (P<0.05) with the prevalence of CKD. Among these polymorphisms, the -219G-->T polymorphism of APOE (rs405509) was most significantly associated with CKD in Japanese individuals with metabolic syndrome.

Association of genetic variants with myocardial infarction in Japanese individuals with chronic kidney disease.

Chronic kidney disease (CKD) is a serious clinical condition that is associated with a high incidence of cardiovascular disease and end-stage renal disease. Although CKD has been recognised as a risk factor for myocardial infarction (MI), genetic factors for predisposition to MI in individuals with CKD have remained largely unknown. The purpose of the present study was to identify genetic variants that confer susceptibility to MI in Japanese individuals with CKD. The study subjects comprised 1,339 Japanese individuals with CKD, including 496 subjects with MI and 843 controls. The genotypes for 248 polymorphisms of 181 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. An initial screen of allele frequencies by the chi-square test revealed that the 11496G-->A (Arg353Gln) polymorphism of F7 (rs6046) was significantly (false discovery rate <0.05) associated with the prevalence of MI in individuals with CKD. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure also revealed that this polymorphism was significantly (p <0.005) associated with MI, with the variant A (Gln) allele protecting against this condition. Determination of genotype for the 11496G-->A (Arg353Gln) polymorphism of F7 may prove informative for assessment of the genetic risk for MI in individuals with CKD.

Association of genetic variants with chronic kidney disease in Japanese individuals with type 2 diabetes mellitus.

Although diabetes mellitus has been recognized as a risk factor for chronic kidney disease (CKD), genetic factors for predisposition to CKD in individuals with diabetes mellitus remain elucidated. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD among individuals with type 2 diabetes mellitus. The study population comprised 1742 Japanese individuals, including 636 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 1106 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 24 polymorphisms of 22 candidate genes were determined. An initial screen of allele frequencies by the Chi-square test revealed that four polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of CKD in individuals with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) polymorphism of FABP2 (rs1799883) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus.