Relationship between Alcohol Intake and Stroke Severity in Japanese Patients: a Sex- and Subtype-Stratified Analysis.

OBJECTIVES: This study aims to clarify the association between alcohol intake and stroke severity at admission and discharge according to sex and stroke subtype in Japanese patients with acute stroke. MATERIALS AND METHODS: We analyzed the data of 199,599 patients registered in the Japan Stroke Data Bank from 1999 to 2018, including sex, age, stroke subtypes (cardioembolic ischemic, noncardioembolic ischemic, hypertensive hemorrhagic, nonhypertensive hemorrhagic, and subarachnoid hemorrhagic), dates of onset and admission, National Institutes of Health Stroke Scale score at admission, modified Rankin Scale score at discharge, and alcohol intake. Multivariable logistic regression analysis adjusted for stroke-related factors was performed to estimate the odds ratios of alcohol intake for stroke severity. RESULTS: In cardioembolic ischemic stroke, a significant protective effect of moderate intake on severity at admission was observed in both sexes. In noncardioembolic ischemic stroke, a significant protective effect on stroke severity at admission was found for each sex. At discharge, the results also showed a significant protective effect for each sex with moderate intake. For both subtypes of ischemic stroke, a J-shaped relationship between alcohol intake and stroke severity at admission and discharge was observed in women and men. In hypertensive hemorrhagic stroke, a significant protective effect was found in men at both admission and discharge. In women, heavy drinking had a significant harmful effect on stroke severity at admission. CONCLUSIONS: Habitual alcohol intake is associated with stroke severity at admission and discharge regardless of sex.

Relationships between Alcohol Intake and Ischemic Stroke Severity in Sex Stratified Analysis for Japanese Acute Stroke Patients.

BACKGROUND: The aim of this study is to evaluate in the relationships between alcohol intake and ischemic stroke severity in Japanese stroke patients. METHODS: Of a total of 101,165 registered cases of stroke in Japan, patient data of total strokes (n = 60,836), cardiogenic strokes (n = 11,894), and noncardiogenic strokes (n = 29,129) were extracted. The National Institutes of Health Stroke Scale (NIHSS) score at admission and the modified Rankin Scale (mRS) score at discharge were used. Significant alcohol consumption in regard to stroke severity at admission and discharge was identified by multivariate adjusted logistic regression analysis. RESULTS: Among all subject and males, nondrinkers had significantly poorer NIHSS scores of cardiogenic strokes as did those consuming greater than or equal to 60 g/day, whereas there was a significant difference in past heavy drinkers with noncardiogenic strokes. Among females, nondrinkers had a significance of cardiogenic stroke and non-cardiogenic strokes. Among all subjects and males, 20-39 g/day and 40-59 g/day were significantly associated with protective effects on mRS severity of cardiogenic strokes, whereas 40-59 g/day also had significant protective effects for noncardiogenic strokes. Among females, greater than or equal to 60 g/day had a significant protective effect for cardiogenic strokes. CONCLUSIONS: For males, alcohol intake of less than 60 g/day played a protective role in functional prognosis at discharge and showed a J-shape relationship. For females, although there was a limitation that the number of female drinkers was small, negative effects were shown at admission with less consumption than males.

A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017.

BACKGROUND: The Consensus Statement from the European Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that low-density lipoprotein (LDL) causes atherosclerotic cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting LDL receptor function were found to cause higher or lower LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of LDL-C exposure and ASCVD risk. The EAS Statement proposes that any mechanism of lowering plasma LDL concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C. However, as we explain, we do not find this conclusion acceptable. SUMMARY: Our review points out that different interpretations are possible for the results of Mendelian randomization studies. As for prospective cohort studies, many inconsistent reports on the association of LDL-C and ASCVD were disregarded when drafting the Statement, reports with and without genetic factors related to LDL receptor function should be analyzed separately, and the term ASCVD in the Statement is used inappropriately because myocardial infarction and cerebral infarction differ in their association with LDL-C. As for RCTs, clinical reports on statins published before and after the implementation of new regulations affecting clinical trials (2004/2005) should not both be included in meta-analyses because the evaluated efficacy of statins changed markedly, and the irreversible adverse effects of statins need to be evaluated more rigorously now that their mechanisms have been elucidated. Key Messages: Apart from the EAS hypothesis that LDL causes ASCVD, recent pharmacological/biochemical studies, as summarized in this review and elsewhere, have revealed that atherosclerosis is caused by statins taken to lower LDL-C, as well as by warfarin and some types of vegetable fats and oils, in the absence of significantly elevated LDL-C levels. Thus, the promotion of statin treatment by the Statement is rather risky and we do not feel that the conclusions are justified for the prevention of ASCVD.

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.

OBJECTIVE: It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue. SETTING, PARTICIPANTS AND OUTCOME MEASURES: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population. RESULTS: We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found. CONCLUSIONS: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.

In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and 'heme A', and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated.

Predicting perioperative venous thromboembolism in Japanese gynecological patients.

OBJECTIVE: To develop a convenient screening method that can predict perioperative venous thromboembolism (VTE) and identify patients at risk of fatal perioperative pulmonary embolism (PE). METHODS: Patients hospitalized for gynecological abdominal surgery (n = 183) underwent hematology tests and multidetector computed tomography (MDCT) to detect VTE. All statistical analyses were carried out using the SPSS software program (PASWV19.0J). RESULTS: The following risk factors for VTE were identified by univariate analysis: plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and prolonged immobility (all p<0.001); age, neoadjuvant chemotherapy (NAC), malignancy, hypertension, past history of VTE, and hormone therapy (all p<0.01); and hemoglobin, transverse tumor diameter, ovarian disease, and menopause (all p<0.05). Multivariate analysis using these factors revealed that PIC, age, and transverse tumor diameter were significant independent determinants of the risk of VTE. We then calculated the incidence rate of perioperative VTE using PIC and transverse tumor diameter in patient groups stratified by age. In patients aged ≤40 years, PIC ≥1.3 µg/mL and a transverse tumor diameter ≥10 cm identified the high-risk group for VTE with an accuracy of 93.6%. For patients in their 50 s, PIC ≥1.3 µg/mL identified a high risk of VTE with an accuracy of 78.2%. In patients aged ≥60 years, a transverse tumor diameter ≥15 cm (irrespective of PIC) or PIC ≥1.3 µg/mL identified the high-risk group with an accuracy of 82.4%. CONCLUSIONS: We propose new screening criteria for VTE risk that are based on PIC, transverse tumor diameter, and age. Our findings suggest the usefulness of these criteria for predicting the risk of perioperative VTE and for identifying patients with a high risk of fatal perioperative PE.

Comparison of eicosapentaenoic acid concentrations in plasma between patients with ischemic stroke and control subjects.

OBJECTIVE: ω-3 fatty acids, including eicosapentaenoic acid (EPA), prevent ischemic stroke. However, the clinical importance of EPA for ischemic stroke and its subtype has not been fully elucidated. METHODS: In a cross-sectional study, we determined whether ω-3 fatty acids were predictive factors for ischemic stroke. We compared common clinical parameters among 65 patients with ischemic stroke and 65 control subjects. The parameters included blood chemistry data; concentrations of EPA, docosahexaenoic acid, and arachidonic acid (AA); EPA/AA ratio; smoking; alcohol intake; fish consumption more than four times per week; and the incidence of underlying diseases. The comparisons were performed using the Mann-Whitney U test, and multiple logistic regression analysis was applied to the significant factors in the non-parametric test. We also applied the same approach to the ischemic stroke subtypes, cardioembolism and large-artery atherosclerosis. RESULTS: In the multiple logistic regression analysis after the Mann-Whitney U test, a lower EPA concentration was one of the significant risk factors for ischemic stroke, as were a lower body mass index, lower high-density lipoprotein cholesterol, and smoking (sensitivity 0.846, specificity 0.831, positive predictive value 0.833). In the analysis of subtypes, a lower EPA/AA ratio and a lower body mass index were the significant risk factors for cardioembolism (sensitivity 0.800, specificity 0.733, positive predictive value 0.750). However, large-artery atherosclerosis was not related to the EPA concentration or the EPA/AA ratio. CONCLUSIONS: In this study, the plasma EPA concentration and the EPA/AA ratio were potential predictive risk factors for ischemic stroke, especially for cardioembolism. Further prospective studies are necessary.

Fasting plasma glucose reference values among young Japanese women requiring 75g oral glucose tolerance tests.

OBJECTIVE: Currently there are various discussions on the upper limit of FPG (Fasting Plasma Glucose) levels. In Japan, when abnormal levels of FPG are detected at general health checkups or complete physical examinations, 75g Oral Glucose Tolerance Tests (75g OGTT) are often conducted in follow-up examinations. Therefore we investigated the appropriate upper limit of FPG levels to decide whether 75g OGTT are actually necessary. RESEARCH DESIGN AND METHODS: Based on the FPG levels of 256,309 women with an age range of 20 to 79, we established the upper limits of FPG levels by 5-year intervals, using a method equivalent to the National Committee for Clinical Laboratory Standards (NCCLS) used in the U. S. [4]. We also obtained the ROC curve from the 75g OGTT results from 160 women aged 20 to 39. We then divided those 160 women into four categories based on their 75g OGTT results, and compared the abnormal rates of their 2-hour post-75g OGTT glucose levels, HOMA-R and Insulin Index using the Kruskal-Wallis test. RESULTS: The upper limits of FPG levels were 99 mg/dl in the 20-29 age range, 101 mg/dl in the 30-34 age range, and 104 mg/dl in the 35-39 age range. The upper limits of the FPG reference intervals increased almost proportionally up to the age 50, and showed little difference thereafter. The point on the ROC curve where the total value of sensitivity plus specificity reached the highest had an FPG level of 99.5 mg/dl. For 2-hour post-75g OGTT glucose levels and HOMA-R, there was a significant difference in abnormal rates between the categories of FPG ≤ 99 mg/dl and 100 ≤ FPG ≤ 109 mg/dl, but not in Insulin Index. CONCLUSIONS: We believe that 75g OGTT are necessary for Japanese women aged 20 to 39 with FPG levels of 100 mg/dl or above.

Radiological reporting that combine continuous speech recognition with error correction by transcriptionists.

OBJECTIVE: We evaluated the usefulness of radiological reporting that combines continuous speech recognition (CSR) and error correction by transcriptionists. MATERIALS AND METHODS: Four transcriptionists (two with more than 10 years' and two with less than 3 months' transcription experience) listened to the same 100 dictation files and created radiological reports using conventional transcription and a method that combined CSR with manual error correction by the transcriptionists. We compared the 2 groups using the 2 methods for accuracy and report creation time and evaluated the transcriptionists' inter-personal dependence on accuracy rate and report creation time. We used a CSR system that did not require the training of the system to recognize the user's voice. RESULTS: We observed no significant difference in accuracy between the 2 groups and 2 methods that we tested, though transcriptionists with greater experience transcribed faster than those with less experience using conventional transcription. Using the combined method, error correction speed was not significantly different between two groups of transcriptionists with different levels of experience. CONCLUSION: Combining CSR and manual error correction by transcriptionists enabled convenient and accurate radiological reporting.

Estimation of sex-age specific clinical reference ranges by nonlinear optimization method.

Most reference ranges are not considered sex-age specific differences. We collected about 700,000 health examination data with 24 items to estimate sex-age specific clinical reference ranges. We proposed nonlinear optimization method as a new method compatible with NCCLS guideline. All items showed sex-age specific differences of reference ranges. Especially, hepatic functions in young aged men and all aged women, diabetic functions in young aged people, blood pressures in older people, and total cholesterol in all aged people might have serious problems. Some abnormal individuals might not be detected using established reference ranges, on the other hand, some normal individuals might be treated excessively.

Evaluation of applied cases of thrombolytic therapy against ultra-acute ischemic stroke. Using the Japanese Standard Stroke Registry Database.

BACKGROUND: A retrospective evaluation was made concerning thrombolytic therapy for ultra-acute ischemic stroke patients, using a recombinant tissue plasminogen activator (rt-PA), which is not yet approved as a drug for brain infarction in Japan. The evaluation was implemented using the database of patients that suffered acute strokes as collected by the Japanese Standard Stroke Registry Study (JSSRS). METHODS: The thrombolytic therapy group, selected from among the registered 6,090 cases of brain infarction patients, was divided into two groups, namely, a group of patients who were admitted in the hospital within 3 hours of the onset (86 cases, average age 69.6) and the other group who were admitted after 3 hours from the onset (28 cases, average age 66.8). Using a Multiple Logistic Regression Analysis adapted for modified Rankin scale (mRS) regarding each group, the clinical effects of thrombolytic therapy for functional outcome and presence or absence of dementia at the time of hospital discharge were examined. Among the 467 cases of patients (average age 74) who were admitted within 3 hours of the onset and for whom the NIH Stroke Scale (NIHSS) was between 6 and 29 at the time of admission, intravenous or intra-arterial thrombolytic therapy was conducted in 88 cases. Then, a case-control study and Multiple Logistic Regression Analysis was implemented for subject groups matched according to the gender, age and severity at the time of admission, and the effects on early-admitted patients were examined. Also, for two rehabilitation patient groups: one whose rehabilitation started within 7 days (216 cases; average age 73) and the other whose rehabilitation started after 7 days (56 cases, average age 76), the effects of early rehabilitation were examined using Multiple Logistic Regression Analysis. Moreover, the effects of thrombolytic therapy on a group of patients who were admitted early and for whom rehabilitation started early (215 cases; average age 73) were examined in the same way. RESULTS: In the comparison between the thrombolytic therapy groups, the functional outcome of the group of patients admitted within 3 hours of the onset at the time of discharge (mRS 0-1) was significantly better compared with that of the group after 3 hours from the onset (OR 2.79, 95% CI: 1.06-7.32). Regarding the comparison between the early admitted patients, the frequency of poor functional outcomes (mRS 2-6) at the time of discharge was significantly lower in the thrombolytic therapy group (OR 0.55, 95% CI 0.31-0.98), and the frequency of dementia was also significantly lower (OR 0.37, 95% CI 0.17-0.86). In the case control study, a significant difference was noted for the presence of dementia. In the group rehabilitation was started early, the frequency of poor functional outcomes was significantly lower (OR 0.33, 95% CI 0.11-0.98), and the frequency of dementia was also significantly lower (OR 0.41, 95% CI 0.19-0.89). As for the comparison of the groups admitted early and for which rehabilitation started early, the frequency of poor functional outcomes at the time of discharge was significantly lower in the thrombolytic therapy group (OR 0.38, 95% CI 0.16-0.86). CONCLUSIONS: From the present analysis, in spite of being a retrospective analysis based on comparatively small number of patient cases from the stroke database, it is concluded that the clinical application of thrombolytic therapy for ultra-acute ischemic strokes was effective. Moreover, it was demonstrated that, if it is possible to start rehabilitation early, a dramatic improvement of the effects might be expected.

Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet.

The role of inducible nitric oxide synthase (iNOS) in the progression of fibrosis during nonalcoholic steatohepatitis remains to be elucidated. This study examined the role of iNOS in the progression of fibrosis during steatohepatitis by comparing iNOS knockout (iNOS(-/-)) and wild-type (iNOS(+/+)) mice that were fed a high-fat diet. Severe fatty metamorphosis developed in the liver of iNOS(+/+) and iNOS(-/-) mice. Fibrotic changes were marked in iNOS(-/-) mice. Gelatin zymography showed that pro MMP-2 and pro MMP-9 protein expressions were more highly induced in iNOS(+/+) mice than in iNOS(-/-) mice. Active forms of MMP-2 and MMP-9 were clearly present only in the liver tissue of iNOS(+/+) mice. In situ zymography showed strong gelatinolytic activities in the liver tissue of iNOS(+/+) mice, but only spotty activity in iNOS(-/-)mice. iNOS may attenuate the progression of liver fibrosis in steatohepatitis, in part by inducing MMP-2 and MMP-9 expression and augmenting their activity.

Association of health-related quality of life with health examination including organic functions and lifestyles in Japanese employees.

OBJECTIVE: The objective of this study was to compare the association of each item of a health examination including organic functions and lifestyles with health-related quality of life (HRQoL) by gender. METHODS: A cross-sectional survey by a self-administered questionnaire using the 36-Item Short Form Health Survey (SF-36) was conducted for Japanese employees from October 1999 to September 2000. Participants in this study consisted of 458 men and 321 women systematically selected from the health examinees. MAIN RESULTS: The determination of organic functions including 'body mass index', 'blood pressure', 'liver functioning', and 'blood sugar control' was hardly associated with HRQoL, except for the body mass index in women. All the lifestyle items including smoking cigarettes, drinking alcohol, eating breakfast, doing exercise, adhering to bedtime, and working overtime were associated with HRQoL in the multiple regression models. In the mental component summary (MCS), the standardized regression coefficient of 'hours of overtime' was -0.235 in the men and -0.212 in the women (p < 0.001). In the physical component summary (PCS), that of 'energy consumed in exercise' was 0.149 in the women (p < 0.01). CONCLUSION: This study reveals that the association between lifestyle and HRQoL was stronger than that between organic function and HRQoL.

Evaluation of image qualities on the international standard video-conferencing.

International standard-based video-conferencing systems are widely used in telemedicine activities worldwide. Through our experiences with these systems, it is apparent that the image quality is high enough to conduct educational and conferential sessions. However, because the terminals are intended for common use, we evaluated their qualities. After having an international standard system evaluated by a general practitioner using medical images, we prepared non-medical graphic images to examine the characteristics of the video-conferencing equipment. ROC (Receiver Operation Characteristic) analysis was employed for the evaluation. We concluded that the international standard video-conferencing systems are of sufficient quality for medical presentations, and that their interactivity and the use of proper software will aid the understanding of images in specific medical areas.