Atrial electrical remodeling and function after transcatheter aortic valve replacement in patients with aortic stenosis.

To examine reverse atrial electrical remodeling in patients with aortic stenosis (AS) after trans-catheter aortic valve replacement (TAVR). In 65 consecutive patients with severe AS (83 ± 4 years, 47 (72.3%) females), we analyzed ECG records for the P wave duration (PWD) in lead II and P-terminal force (PTFV1) in V1, and measured cardiac dimensions and function by echocardiography (ECHO) following TAVR. Biomarkers were measured to assess myocardial injury by TAVR. TAVR was successfully performed without major complications: the aortic valve area increased from 0.62 ± 0.14 cm2 to 1.52 ± 0.24cm2, and the trans-aortic pressure gradient decreased from 58.4 ± 15.9 mmHg to 15.0 ± 19.6 mmHg. PWD and PTFV increased immediately after TAVR and returned to the pre-TAVR levels on the next day. Then, the PWD declined toward 6 months after TAVR non-significantly in all patients, but significantly in 25 patients with baseline PWD ≥ 130 ms (P = 0.039). PTFV1 showed no long-term change. Improvement was observed in the ejection fraction, all thickness of the left ventricle and in the left atrial dimensions on ECHO. After recovery from transient aggravation by TAVR procedure, PWD reversed slowly, and the change was significant in those with baseline PWD ≥ 130 ms while change in PTFV1 was not significant at 6 months of follow-up. ECHO showed a reversal of remodeling in the left ventricle and in the left atrial dimension after TAVR.

Utility of a Physical Fitness Score in Screening for Chronic Diseases.

We developed a new Physical Score (PS) consisting of comprehensive physical fitness indicators and elucidated the association between the resultant PS and metabolic diseases, i.e., diabetes, hypertension, dyslipidemia, fatty liver, and metabolic syndrome (MetS), among Japanese. Analyzed were 49,850 persons (30,039 men) aged 30 to 69 y who underwent physical fitness tests. Principal component analysis was performed on the correlation matrix of the physical fitness test results (relative grip strength, single-leg balance with eyes closed, and forward bending) according to sex and age. We defined the PS as the first principal component score. A formula was developed for various age groups comprised of men and women from 30 to 69 years of age from which the PS for each age and sex was calculated. The PS for both men and women was normally distributed with a value of 0 ± 1.15-1.16. Multivariate logistic regression analysis showed that the risk of metabolic diseases increased approximately 1.1-1.6 times per each 1-point reduction in the PS. The association between PS and MetS was particularly strong in that a 1-point reduction in the PS increased the risk of MetS by 1.54 times (95% confidence interval 1.46 to 1.62) in men and by 1.21 times (1.15 to 1.28) in women. The association between a lower PS and disease risk was stronger in younger men for fatty liver and in older men for MetS. Conversely, in women, the association between a lower PS and disease risk was stronger in older women for fatty liver and in younger women for MetS. For diabetes, hypertension, and dyslipidemia, the change in the impact of PS reductions across age groups was small. The PS is a useful and simple non-invasive tool for screening Japanese people for metabolic diseases.

Leisure-time physical activity and incidence of objectively assessed hearing loss: The Niigata Wellness Study.

Previous cohort study reported that high physical activity was associated with a low risk of self-reported hearing loss in women. However, no studies have examined the association between physical activity and the development of hearing loss as measured using an objective assessment of hearing loss in men and women. Here, we used cohort data to examine the association between leisure-time physical activity and incidence of objectively assessed hearing loss in men and women. Participants included 27 537 Japanese adults aged 20-80 years without hearing loss, who completed a self-administered physical activity questionnaire between April 2001 and March 2002. The participants were followed up for the development of hearing loss as measured by audiometry between April 2002 and March 2008. During follow-up, 3691 participants developed hearing loss. Compared with the none physical activity group, multivariable adjusted hazard ratios (HRs) for developing hearing loss were 0.93 (95% confidence interval (CI), 0.86-1.01) and 0.87 (0.81-0.95) for the medium (<525 MET-min/week) and high (≥525 MET-min/week) physical activity groups, respectively (p for trend = 0.001). The magnitude of risk reduction was slightly greater in vigorous-intensity activity than in moderate-intensity activity (p for interaction = 0.01). Analysis by sound frequency showed that the amount of physical activity was inversely associated with high frequency hearing loss development (p for trend <0.001), but not with low frequency hearing loss development (p for trend = 0.19). Higher level of leisure-time physical activity was associated with lower incidence of hearing loss, particularly for vigorous-intensity activities and high sound frequencies.

Prediabetes is associated with proteinuria development but not with glomerular filtration rate decline: A longitudinal observational study.

AIMS: Diabetes is recognized as the leading cause of chronic kidney disease (CKD); however, the association of prediabetes with CKD remains unclear, in particular, the independent effect of prediabetes on proteinuria or estimated glomerular filtration rate (eGFR) has not been evaluated. This study aimed to investigate the associations of prediabetes with the proteinuria development and with eGFR decline separately in the Japanese general population without CKD. METHODS: Participants who underwent health check-ups in 2014 and had adequate data after 2 years were retrospectively analysed. A total of 405,487 participants without CKD (eGFR, ≥60 ml min-1  1.73 m-2 , with negative or trace urinary protein) at baseline were categorized according to fasting plasma glucose as having diabetes (≥126 mg/dl [7.0 mmol/l]), prediabetes (100-125 mg/dl [5.6-6.9 mmol/l]) or normal glucose level (˂100 mg/dl [5.6 mmol/l]). Logistic regression analysis was used to analyse the effects of prediabetes (vs. normal glucose level) on the proteinuria development (urinary protein of ≥1+) and eGFR decline (˂60 ml min-1  1.73 m-2 ) after 2 years. RESULTS: After 2 years, 7037 participants (1.7%) developed proteinuria alone, 19,015 (4.7%) presented eGFR decline alone and 636 (0.2%) showed both proteinuria and eGFR decline. Compared to normal glucose level and adjusting for prognostic factors, prediabetes was independently associated with the proteinuria development (odds ratio [OR] 1.233; 95% confidence interval [CI] 1.170-1.301], whereas prediabetes was not associated with eGFR decline (OR 0.981; 95% CI 0.947-1.017). CONCLUSIONS: Prediabetes is associated with the proteinuria development but not with eGFR decline in the general population.

Healthy lifestyle reduces incidence of trace/positive proteinuria and rapid kidney function decline after 2 years: from the Japan Ningen Dock study.

BACKGROUND: Lifestyle modification is recommended for subjects with trace proteinuria during health checkups. However, whether overall healthy lifestyle reduces the incidence of trace/positive proteinuria or rapid decline in estimated glomerular filtration rate (eGFR) is not clarified. METHODS: A total of 451 534 people (277 494 men and 174 040 women) ages 20-79 years with negative proteinuria were included. The number of three healthy lifestyle factors (LFs) was assessed: noncurrent smoking, healthy eating habits (late dinner, snacking and skipping breakfast <3 times/week) and body mass index <25. The incidence of trace (±) and positive (≥1+) proteinuria by the dipstick method and eGFR decline ≥20% over 2 years were compared with the number of healthy LFs. RESULTS: The incidence of trace/positive proteinuria and rapid eGFR decline decreased with an increasing number of healthy LFs as follows: odds ratios (ORs) for trace proteinuria, 0.91 [95% confidence interval (CI) 0.86-0.96], 0.82 (0.78-0.87) and 0.72 (0.68-0.77); ORs for positive proteinuria, 0.76 (95% CI 0.67-0.86), 0.56 (0.50-0.63) and 0.46 (0.40-0.53); and ORs for an eGFR decline ≥20%, 0.93 (95% CI 0.82-1.05), 0.90 (0.79-1.02) and 0.81 (0.70-0.93) for those with one, two and three healthy LFs compared with those with none of the three healthy LFs, respectively. Overall, subjects with a healthy lifestyle showed 28, 54 and 19% reduced risk of developing trace proteinuria, positive proteinuria and eGFR decline ≥20%, respectively, compared with those with an unhealthy lifestyle after 2 years. This association was similarly observed even among subjects without hypertension (HT) or diabetes mellitus (DM). CONCLUSIONS: Subjects with an overall healthy lifestyle showed a lower incidence of trace/positive proteinuria by dipstick test and rapid eGFR decline over 2 years in a nationwide general population. Thus lifestyle modification should be recommended for subjects with trace proteinuria during health checkups, even for subjects without HT or DM.

Physical Fitness and Dyslipidemia Among Japanese: A Cohort Study From the Niigata Wellness Study.

BACKGROUND: Grip strength reflects systemic muscle strength and mass and is reportedly associated with various metabolic variables. However, its prognostic association with dyslipidemia is unknown. We examined the association of grip strength and other physical fitness markers with the incidence of dyslipidemia among Japanese adults. METHODS: A total of 16,149 Japanese (6,208 women) individuals aged 20-92 years who underwent a physical fitness test between April 2001 and March 2002 were included in this cohort study. Grip strength, vertical jump, single-leg balance with eyes closed, forward bending, and whole-body reaction time were evaluated at baseline. Dyslipidemia was annually determined based on fasting serum lipid profiles and self-reported dyslipidemia from April 2001 to March 2008. RESULTS: During the follow-up period, 4,458 (44.9%) men and 2,461 (39.6%) women developed dyslipidemia. A higher relative grip strength (grip strength/body mass index) was associated with a lower incidence of dyslipidemia among both men and women (P for trend <0.001). Compared with those for the first septile, the hazards ratios and 95% confidence intervals (CIs) for the seventh septile were 0.56 (95% CI, 0.50-0.63) for men and 0.69 (95% CI, 0.58-0.81) for women. Moreover, relative vertical jump (vertical jump strength/body mass index) was also inversely associated with the incidence of dyslipidemia among both men and women (P for trend <0.001). There was no association between other physical fitness and dyslipidemia among both men and women. CONCLUSION: Relative grip strength and vertical jump may be useful risk markers of the incidence of dyslipidemia.

Body flexibility and incident hypertension: The Niigata wellness study.

A high level of physical fitness, especially cardiorespiratory fitness, is associated with lower incidence of hypertension. However, the relationship between flexibility, which is a component of physical fitness, and the incidence of hypertension is unknown. The purpose of this study was to investigate the relationship between flexibility and the incidence of hypertension in a cohort study. A total of 22,972 (14,805 men and 8167 women; median age 49 years) normotensive participants were included in this study. Between April 2001 and March 2002, flexibility (standing forward bending) was measured using a standing trunk flexion meter. The participants were divided into quartiles of flexibility by sex and age group. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg, or a self-reported history of previously diagnosed hypertension or current medication for hypertension at a health examination between April 2002 and March 2008. Hazard ratios and 95% confidence intervals (95% CI) for the incidence of hypertension were estimated using Cox proportional hazards models after adjusting for age, sex, body mass index, exercise habits, smoking status, and drinking status. During 102,948 person years of follow-up (median 5.6 years), 4235 participants developed hypertension. Compared with the lowest flexibility (quartile 1), hazard ratios and 95% CI were 0.96 (0.88 - 1.04) for quartile 2, 0.94 (0.86 - 1.03) for quartile 3, and 0.83 (0.76 - 0.91) for quartile 4. A high level of flexibility was associated with lower incidence of hypertension, independent of other confounding factors.

Meta-regression Analysis of Sex- and Birth Year-Specific Prevalence of HBsAg and Anti-HCV Among Un-diagnosed Japanese: Data From the First-time Blood Donors, Periodical Health Checkup, and the Comprehensive Health Checkup With Lifestyle Education (Ningen Dock).

BACKGROUND: This study was aimed to precisely estimate the prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV) stratified by sex and birth year in Japan. METHODS: Three large-scaled cohorts: first-time blood donors, periodic health check-up, and comprehensive health check-up with lifestyle education (Ningen dock) were used for pooled prevalence of HBsAg and anti-HCV using meta-regression. RESULTS: Trends of birth year-specific prevalence of HBsAg and anti-HCV among the three cohorts were similar to one another, while birth year-specific pooled prevalence of HBsAg peaked in the 1941-1950 birth cohort. Prevalence of anti-HCV showed a decreasing trend by birth year. CONCLUSION: We could estimate the pooled prevalence of HBsAg and anti-HCV based on nationwide data. The results can be used as reference data for various countermeasures for hepatitis eradication.

Physical Fitness Tests and Type 2 Diabetes Among Japanese: A Longitudinal Study From the Niigata Wellness Study.

BACKGROUND: Simple physical fitness test can be a useful potential predictor of type 2 diabetes (T2DM). We examined the association between performances on simple physical fitness tests and the incidence of T2DM. METHODS: This longitudinal study was conducted in 21,802 nondiabetic Japanese (6,649 women) aged 20 to 92 years, who underwent all physical fitness tests at baseline (April 2001 to March 2002). From April 2001 to March 2008, physical fitness tests, including grip strength, vertical jump, single-leg balance with eyes closed, forward bending, whole-body reaction time, and supine legs-up, were performed every year. Participants had physical fitness tests at least two times during the period. T2DM was also annually determined based on fasting blood glucose, glycated hemoglobin, and self-reported diabetes during the period. Discrete-time logit models were used to examine the influence of the serial level of each physical fitness test on the incidence of T2DM. RESULTS: During the entire study period, 972 participants developed diabetes. Lower relative grip strength (grip strength/body weight) and single-leg balance performance were associated with a higher incidence of T2DM. For relative grip strength, as compared with the fourth quartile group, the odds ratios for other groups ranged from 1.16 to 1.56 (P for trend < 0.001). For single-leg balance, the odds ratios ranged from 1.03 to 1.49 (P for trend < 0.001). CONCLUSION: The performance of a simple single-leg balance test as well as that of a grip strength test were negatively associated with the risk of T2DM among Japanese.

Effect of family-oriented diabetes programs on glycemic control: A meta-analysis.

BACKGROUND: Efficacy of programs for patients with diabetes mellitus (DM) that have promoted family members to help with patients' self-care activities has been largely inconsistent. This meta-analysis aims to assess the effect of family-oriented diabetes programs for glycemic control (GC). METHODS: Electronic literature searches were conducted for clinical trials with a parallel design wherein there were two groups according to whether family members were included (intervention group) or not included (control group) and changes in glycohemoglobin A1C (A1C) were assessed as a study outcome. Each effect size (i.e. difference in A1C change between the intervention and control group) was pooled with a random-effects model. RESULTS: There were 31 eligible trials consisting of 1466 and 1415 patients in the intervention and control groups, respectively. Pooled A1C change [95% confidence interval (CI)] was -0.45% (-0.64% to -0.26%). Limiting analyses to 21 trials targeted at patients with type 1 DM or 9 trials targeted at patients with type 2 DM, the pooled A1C changes (95% CI) were -0.35% (-0.55% to -0.14%) and -0.71% (-1.09% to -0.33%), respectively. CONCLUSION: This meta-analysis suggests that focusing on the family as well as the individual patient in self-management diabetes programs to improve the performance of self-care activities of patients with DM is effective in terms of proper GC.

Asymptomatic Coronary Artery Disease in Japanese Patients With the Acute Ischemic Stroke.

OBJECTIVE: To investigate the prevalence and outcomes of asymptomatic coronary artery disease (CAD) in patients with the first episode of ischemic stroke. METHODS: Patients admitted to our hospital between November 2001 and January 2009 for the episode of an acute ischemic stroke/transient ischemic attack were included. Stress-Tl-201 scintigraphy was performed and followed by coronary angiography (CAG). The prevalence and risks for asymptomatic CAD, and long-term outcomes were studied. RESULTS: Of 1309 patients, only 15 (1.1%) patients presented with a history of CAD. Excluding 406 patients because of severity, systemic infection, early transfer to another hospital, or a refusal to participate, myocardial scintigraphy was performed in 903 patients (mean age, 72 ± 10 years, male 63.9%), and myocardial ischemia was diagnosed in 214 patients (23.7%). Of these patients, 76 patients underwent CAG, and showed significant stenosis (>75%) of a coronary artery in 61 (80.3%) patients. The risk factors for positive scintigraphy findings and CAG were high-grade premature complexes via Holter monitoring (P < .0001), enlarged left ventricle (P = .0051) and wall motion abnormalities (P = .0014) observed on echocardiography, and carotid artery stenosis observed in magnetic resonance angiography imaging (P < .0001). During the follow-up periods of 83 ± 47 months and of 91 ± 47 months, 17.2% of scintigraphy-positive and 2.8% of scintigraphy-negative patients developed episodes of myocardial ischemia, respectively (P < .001). CONCLUSIONS: Symptomatic CAD was rare in Japanese patients with the first episode of ischemic stroke, but asymptomatic CAD was identified by stress Tl-201 myocardial scintigraphy in one-quarter of the patients. Positive scintigraphy was associated with asymptomatic CAD and future cardiac events.

Low-Dose Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction (EPO-AMI-II)　- A Randomized Controlled Clinical Trial.

BACKGROUND: Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results:We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events. CONCLUSIONS: Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13-1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08-1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus.

BACKGROUND: Our aim is to examine the dose-response association between cumulative genetic risk and actual risk of type 2 diabetes mellitus (T2DM) and the influence of adjustment for covariates on T2DM risk through a comprehensive meta-analysis of observational studies. METHODS: Electronic literature search using EMBASE and MEDLINE (from 2003 to 2014) was conducted for cross-sectional or longitudinal studies that presented the odds ratio (OR) for T2DM in each group with categories based on the total number of risk alleles (RAs) carried (RAtotal ) using at least two single-nucleotide polymorphisms. Spline regression model was used to determine the shape of the relationship between the difference from the referent group of each study in RAtotal (ΔRAtotal ) and the natural logarithms of ORs (log OR) for T2DM. RESULTS: Sixty-five eligible studies that included 68 267 cases among 182 603 participants were analysed. In both crude and adjusted ORs, defined by adjusting the risk for at least two confounders among age, gender and body mass index, the slope of the log OR for T2DM became less steep as the ΔRAtotal increased. In the analysis limited to 14 cross-sectional and four longitudinal studies presenting both crude and adjusted ORs, regression curves of both ORs in relation to ΔRAtotal were almost identical. CONCLUSION: Using only single-nucleotide polymorphisms for T2DM screening was of limited value. However, when genotypic T2DM risk was considered independently from risk in relation to covariates, it was suggested that genetic profiles might have a supplementary role related to conventional T2DM risk factors in identifying individuals at high risk of T2DM. Copyright © 2015 John Wiley & Sons, Ltd.

Utility of nonblood-based risk assessment for predicting type 2 diabetes mellitus: A meta-analysis.

OBJECTIVE: Nonblood-based risk assessment for type 2 diabetes mellitus (T2DM) that depends on data based on a questionnaire and anthropometry is expected to avoid unnecessary diagnostic testing and overdiagnosis due to blood testing. This meta-analysis aims to assess the predictive ability of nonblood-based risk assessment for future incident T2DM. METHODS: Electronic literature search was conducted using EMBASE and MEDLINE (from January 1, 1997 to October 1, 2014). Included studies had to use at least 3 predictors for T2DM risk assessment and allow reproduction of 2×2 contingency table data (i.e., true positive, true negative, false positive, false negative) to be pooled with a bivariate random-effects model and hierarchical summary receiver-operating characteristic model. Considering the importance of excluding individuals with a low likelihood of T2DM from diagnostic blood testing, we especially focused on specificity and LR-. RESULTS: Eighteen eligible studies consisting of 184,011 participants and 7038 cases were identified. The pooled estimates (95% confidence interval) were as follows: sensitivity=0.73 (0.66-0.79), specificity=0.66 (0.59-0.73), LR+=2.13 (1.81-2.50), and LR-=0.41 (0.34-0.50). CONCLUSIONS: Nonblood-based assessment of risk of T2DM could produce acceptable results although the feasibility of such a screener needs to be determined in future studies.

Integrating Community Care for the Prevention and Treatment of Diabetes.

Introduction: This paper describes 'Project 8', a campaign that aims to reduce glycated haemoglobin (HbA1c) to 8% or more among patients with diabetes mellitus, utilising healthcare professionals and local community residents and focusing on education and support. The study is based in Uonuma-a small rural city in Japan with a declining population and an increased number of older people. Description: 'Project 8' began in Uonuma's Koide Hospital in 2008. The Uonuma School for Community Health and Social Care was established in 2011 with the cooperation of a clinic's general practitioner. Medical students, trainees, doctors, and health care professionals have been holding 'open schools' (daytime lectures) and 'night schools' (evening lectures) to educate the community residents about various health issues. Through repeated lectures, the residents have been made aware of lifestyle-related diseases, including diabetes, and the meaning of 'Project 8'. Discussion: Over the last decade, the hospital's campaign has expanded within the community, showing a statistically significant reduction of diabetic patients with HbA1c ≥ 8%, which successfully deferred the start of dialysis for many of them. Conclusion: Well-integrated community care requires interprofessional education, collaborative practice, and the participation of community residents in health education.

Association Between Days of the Week and Intraocular Pressure: Japan Ningen Dock Study.

PRCIS: The analysis of intraocular pressure (IOP) by day of the week using the mega database showed a periodic weekly pattern with the highest value on Monday. PURPOSE: To evaluate IOP by the day of the week. PATIENTS AND METHODS: Annual health checkup examinees between April 2014 and March 2015 were cross-sectionally evaluated. As a result, 655,818 participants [51.5±10.5 (range: 20-96) years, 40.1% women] from 103 medical centers were included. IOP was measured using a noncontact tonometer. The mean IOPs of each day of the week were compared using multiple comparison test and multiple linear regression analysis. Wednesday was set as the reference. Moreover, weekly IOP variations stratified by sex and age were also evaluated. RESULTS: Mean IOPs from Monday to Sunday were 13.19±2.97, 13.06±2.92, 13.05±2.91, 13.05±2.92, 13.12±2.94, 13.10±2.96, and 13.16±2.78 mm Hg. IOP was significantly higher on Monday, Friday, and Saturday than those on Wednesday ( P <0.001, <0.001, 0.002). After adjusting for factors affecting IOP, the IOPs on Monday and Saturday were higher than those on Wednesday [ß=0.097 (95% CI: 0.074-0.121), P <0.001; ß=0.032 (95% CI: 0.005-0.059), P =0.019]. Men had significantly higher IOPs on Monday and Saturday than on Wednesday [ß=0.142 (95% CI: 0.110-0.173), P <0.001; ß=0.053 (95% CI: 0.017-0.089), P =0.004], whereas women did not have a significant trend. Participants aged below 65 years had higher IOPs on Monday ( P <0.001 in under 60 years; P =0.003 in 60-64 years), while those aged 65 years or older did not ( P =0.856). CONCLUSION: IOP values may have a periodic weekly pattern. The high IOP on Monday was more pronounced in men aged less than 65 years.

Usefulness of New Criteria for Metabolic Syndrome Optimized for Prediction of Cardiovascular Diseases in Japanese.

AIMS: We attempted to clarify whether the multiple criteria for metabolic syndrome (MetS) can sufficiently predict cardiovascular disease, whether waist circumference (WC) should be required, and whether sex-specific thresholds for each component are necessary. Only a few large-scale studies among East Asians have addressed the ability of MetS to predict cardiovascular disease. METHODS: We analyzed the data of 330,051 men and 235,028 women aged 18-74 years with no history of coronary artery disease (CAD) or cerebrovascular disease (CVD) from a nationwide Japanese claims database accumulated during 2008-2016. The association of each MetS component with CAD or CVD (CAD/CVD), MetS associated with CAD/CVD according to various criteria, and utility of modified criteria with more specific optimal values for each component were examined using multivariate Cox regression and receiver operating characteristic (ROC) analysis. RESULTS: During the study, 3,934 men (1.19%) and 893 women (0.38%) developed CAD/CVD. For each current MetS criteria, there was a 1.3- to 2.9-fold increased risk of CAD/CVD. Optimal thresholds for predicting CAD/CVD were WCs of 83 and 77 cm, triglycerides levels of 130 and 90 mg/dl, high-density lipoprotein cholesterol levels of 50 and 65 mg/dl, blood pressures of 130/80 and 120/80 mmHg, and fasting plasma glucose levels of 100 and 90 mg/dl for men and women, respectively. The existing MetS criteria and modified criteria were not significantly different in predicting CAD/CVD, but using the modified criteria markedly increased the prevalence of MetS and percentage of people with MetS developing CAD/CVD. CONCLUSIONS: Although various criteria for MetS similarly predicted CAD/CVD, the new criteria greatly reduced the number of high-risk individuals, especially women, overlooked by the current criteria.

Cross-Sectional and Longitudinal Associations between Forearm Bone Mineral Density and Anthropometry in Adult Japanese Men and Women.

BACKGROUND: No consensus exists regarding which anthropometric measurements are related to bone mineral density (BMD), and this relationship may vary according to sex and age. A large Japanese cohort was analyzed to provide an understanding of the relationship between BMD and anthropometry while adjusting for known confounding factors. METHODS: Our cohort included 10,827 participants who underwent multiple medical checkups including distal forearm BMD scans. Participants were stratified into four groups according to age (≥50 years or <50 years) and sex. The BMD values were adjusted for confounding factors, after which single and partial correlation analyses were performed. The prevalence of osteopenia was plotted for each weight index (weight or body mass index [BMI]) class. RESULTS: Cross-sectional studies revealed that weight was more favorably correlated than BMI in the older group (R=0.278 and 0.212 in men and R=0.304 and 0.220 in women, respectively), whereas weight and BMI were weakly correlated in the younger age groups. The prevalence of osteopenia exhibited a negative linear relationship with weight among older women ≥50 years of age, and an accelerated increase was observed with decreasing weight in older men weighing <50 kg and younger women weighing <60 kg. When weight was replaced with BMI, the prevalence was low in most subgroups classified by weight. CONCLUSIONS: Weight, rather than BMI, was the most important indicator of osteopenia but it might not be predictive of future bone loss.

Asialoerythropoietin exerts stronger angiogenic activity than erythropoietin via its binding affinity to tissue.

PURPOSE: Although erythropoietin (EPO) is known to express angiogenic and cardioprotective effects, it also induces hypertension, polycythemia, and platelet activation, which may cause serious adverse effects in patients with cardiovascular diseases. We compared the angiogenic effects of EPO and its nonerythropoietic derivative, asialo-EPO (AEPO). METHODS: Lower limb ischemia was induced in ICR and C57/BL mice. Mice were injected intramuscularly with 2 µg/kg of EPO derivatives for 6 or 7 days. To assess biological differences, the tissue affinity of both EPO derivatives was analyzed in vitro using heparin affinity column chromatography. Tissue affinity was also analyzed in vivo using an intramuscular pharmacokinetic study. RESULTS: The survival of ischemic legs was better in the AEPO group than that in the EPO group (5/13 = 38.5 % vs 1/13 = 7.7 %, p < 0.05), and an increase in regenerated vessels was observed in the AEPO group, but not in the EPO group in ICR mice. Vessel/muscle ratios in control, EPO, and AEPO groups were 0.50 ± 0.34, 0.61 ± 0.32, and 2.83 ± 1.13, respectively (p < 0.0001). On the other hand, regenerated vessels were observed in both EPO and AEPO groups (p < 0.001) in C57/BL mice. AEPO, but not EPO, expressed heparin affinity in vitro. Intramuscularly injected EPO gradually decreased in muscle tissue, while AEPO was maintained at 2.5 ng/muscle for 1 day after several hours of a rapid clearance phase in vivo. CONCLUSIONS: AEPO exerts stronger angiogenic effects than those of EPO presumably via its tissue affinity. Administration of AEPO is a promising option for the treatment of patients with critical limb ischemia.