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The association between physical activity volume or intensity and mortality in general population with impaired renal function is unclear. We assessed these relationships among Japanese residents with impaired renal function.We analyzed 638 individuals with estimated creatinine clearance below 60 ml/min in the Jichi Medical School cohort study. Exposures included the daily amount of physical activity converted to the physical activity index (PAI) used in the Framingham study and the activity time for each intensity. Physical activity intensity was classified into sedentary and nonsedentary. Nonsedentary activity was further divided into light-intensity and moderate-to-vigorous physical activity (MVPA). The outcome was all-cause mortality. Quartiles of the exposures were created, and hazard ratios (HRs) were calculated using the Cox proportional hazards model.The mean age of the subjects was 63.3 years, and 72.4% were female. In total, 172 deaths were registered during 11,567 person-years. No significant association was found between PAI and mortality. A significant association was found between long sedentary time and increased mortality (p = 0.042). Regarding nonsedentary activity, the HRs [95% confidence intervals (CIs)] for Q2, Q3, and Q4 versus Q1 were 0.85 (0.55-1.31), 0.67 (0.41-1.08), and 0.90 (0.54-1.45), respectively. In the subdivided analysis for light-intensity activity, the HRs (95% CIs) of Q2, Q3, and Q4 versus Q1 were 0.53 (0.33-0.84), 0.51 (0.34-0.82), and 0.57 (0.34-0.96), respectively. No significant association was found between MVPA and mortality.Nonsedentary activity, especially light-intensity activity, significantly reduced mortality among residents with impaired renal function.

Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, the NAb prevalence in the target population is vital in designing clinical trials with AAV vectors. Hence, updating the seroprevalence of anti-AAV NAbs, herein we analyzed sera from 100 healthy individuals and 216 hemophiliacs in Japan. In both groups, the overall seroprevalence against various AAV serotypes was 20%–30%, and the ratio of NAb-positive population increased with age. The seroprevalence did not differ between healthy participants and hemophiliacs and was not biased by the concomitant blood-borne viral infections. The high neutralizing activity, which strongly inhibits the transduction with all serotypesin vitro, was mostly found in the 60s or older age. The multivariate analysis suggested that “60s or older age” was the only independent factor related to the high titer of NAbs. Conversely, a large proportion of younger hemophiliacs was seronegative, rendering them eligible for AAV-mediated gene therapy in Japan. Compared with our previous study, the peak of seroprevalences has shifted to older populations, indicating natural AAV exposure in the elderly has occurred in their youth but not during the last decade.

It remains to be fully elucidated whether nutrition education by dietitians can lead to specific positive changes in the food choices of patients with diabetes.A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit and the control group that received nutritional education once a year. The total energy intake, energy-providing nutrients and 18 food groups were analyzed at baseline, and 1 and 2 years after the intervention in 87 patients. Furthermore, the relationship between the changes in hemoglobin A1c, body composition and changes in the total energy or energy-producing nutrient intake was analyzed in 48 patients who did not use or change hypoglycemic agents during the study period.The total energy intake, carbohydrates, cereals, confections, nuts and seeds, and seasonings significantly decreased, and fish and shellfish intake significantly increased during the study period in the intensive intervention group, whereas these changes were not observed in the control group. The decrease in the total energy intake and carbohydrates after 2 years was significantly greater in the intensive intervention group than in the control group. The change in the total energy and carbohydrate intake showed a significant positive correlation with that in muscle mass. The multivariate analysis showed that the decrease in total energy intake was independently associated with that in muscle mass.Dietitian-supported intensive dietary intervention helps improve the diet of patients with type 2 diabetes.

The triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is a predictor of metabolic syndrome and cardiovascular disease onset. However, the relationship between TG/HDL-C and stroke has not been established. This study examined whether TG/HDL-C helps in predicting stroke onset; this was compared between the whole population and healthy body mass index (BMI) population.The Jichi Medical School Cohort Study is a prospective cohort study involving baseline data collected in 12 Japanese districts between April 1992 and July 1995. We used data from 11,699 participants; participants with a healthy BMI (20.0-24.9 kg/mIncreased TG/HDL-C correlated with a significant increase in stroke risk only in the healthy BMI population and not the whole population. Furthermore, it was primarily associated with increased intracerebral hemorrhage and cerebral infarction risk.

BACKGROUND Sleeping pills are widely used for sleep disorders and insomnia. This population-based study aimed to evaluate the association between the use of sleeping pills and metabolic syndrome (MetS) and metabolic components in an apparently healthy Japanese cohort. METHODS We examined baseline cross-sectional data from the JMS-II Cohort Study. The criteria for MetS and its components were based on The National Cholesterol Education Program Adult Treatment Panel III. Sleep habits including the sleep duration of the subjects and the frequency of sleeping pill use were obtained using The Pittsburgh Sleep Quality Index questionnaire. For different sleep durations, the association between sleeping pill use and MetS was assessed. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using multiple logistic regression models to quantify this association. RESULTS Our study included 6,153 individuals (mean age, 63.8 [standard deviation 11.2] years), and 3,348 (54.4%) among them were women. The association between sleep duration and MetS was an inverted J-shaped curve among sleeping pill users and a J-shaped curve among non-users. After adjustment for various confounders, less than 6 h of sleep among sleeping pill users was associated with increased rates of MetS (< 6 h, OR [95% CI]: 3.08 [1.29-7.34]). The frequency of sleeping pill use in individuals with short sleep duration showed a positive association with the prevalence of MetS and its components. CONCLUSIONS Sleeping pill users with a short sleep duration had a 3-fold higher chance of having MetS than non-users with a short sleep duration.

Introduction: Previous studies indicate that professional identity formation (PIF), the formation of a self-identity with the internalised values and norms of professionalism, may influence self-regulated learning (SRL). However, it remains unclear whether a PIF-oriented intervention can improve SRL in clinical education. The aim of this study was to explore whether a PIF-oriented mentoring platform improves SRL in a clinical clerkship. Methods: A mixed-methods study was conducted. Forty-one students in a community-based clinical clerkship (CBCC) used a PIF-oriented mentoring platform. They articulated the values and norms of professionalism in a professional identity essay, elaborated on future professional self-image, and reflected on their current compared to future selves. They made a study plan while referring to PIF-based self-reflection and completed it. The control group of 41 students completed CBCC without the PIF-oriented mentoring platform. Changes in SRL between the two groups were quantitatively compared using the Motivated Strategies for Learning Questionnaire. We explore how PIF elements in the platform affected SRL by qualitative analysis of questionnaire and interview data. Results: A moderate improvement in intrinsic goal orientation (p = 0.005, ε2 = 0.096) and a mild improvement in critical thinking (p = 0.041, ε2 = 0.051) were observed in the PIF-oriented platform group. Qualitative analysis revealed that the PIF-oriented platform fostered professional responsibility as a key to expanding learning goals. Gaining authentic knowledge professionally fostered critical thinking, and students began to elaborate knowledge in line with professional task processes. Conclusion: A PIF-oriented mentoring platform helped students improve SRL during a clinical clerkship.

For people who are malnourished and unable to consume food by mouth, nasoenteral feeding tubes are commonly used for the administration of liquid food and drugs. Postpyloric placement is when the tip of the feeding tube is placed beyond the pylorus, in the small intestine. Endoscopic-guided placement of postpyloric feeding tubes is the most common approach. Usually, an endoscopist and two or more medical professionals perform this procedure using a guidewire technique. The position of the tube is then confirmed with fluoroscopy or radiography, which requires moving people undergoing the procedure to the radiology department. Alternatively, electromagnetic-guided placement of postpyloric nasoenteral feeding tubes can be performed by a single trained nurse, at the bedside and with less equipment than endoscopic-guided placement. Hence, electromagnetic-guided placement may represent a promising alternative to endoscopic-guided placement, especially in settings where endoscopy and radiographic facilities are unavailable or difficult to access.To assess the efficacy and safety of electromagnetic-guided placement of postpyloric nasoenteral feeding tubes compared to endoscopic-guided placement.We searched the Cochrane Library, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey until February 2021. We screened the reference lists of relevant review articles and current treatment guidelines for further literature. We contacted the study authors for missing data.We included randomised trials comparing electromagnetic-guided placement with endoscopic-guided placement of nasoenteral feeding tubes. We excluded prospective cohort studies, retrospective cohort studies, (nested) case-control studies, cross-sectional studies, and case series or case reports.Two review authors independently assessed the methodological quality of potentially eligible trials and extracted data from the included trials. The primary outcomes were technical success in insertion and aspiration pneumonitis. The secondary outcomes were the time for postpyloric placement of nasoenteral feeding tubes, direct healthcare costs, and adverse events. We performed a random-effects meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. We evaluated the certainty of evidence based on the GRADE approach.We identified four randomised controlled trials with 541 participants which met our inclusion criteria. All trials had methodological limitations, and lack of blinding of participants and investigators was a major source of bias. We had 'some concerns' for the overall risk of bias in all trials. Electromagnetic-guided postpyloric placement of nasoenteral feeding tubes may result in little to no difference in technical success in insertion compared to endoscopic-guided placement (RR 1.09, 95% CI 0.88 to 1.35; IWe found low-certainty evidence that electromagnetic-guided placement at the bedside results in little to no difference in technical success in insertion and aspiration pneumonitis, compared to endoscopic-guided placement. The heterogeneity of the healthcare professionals who performed the procedures and the small sample sizes limited our confidence in the evidence. Future research should be based on large studies with well-defined endpoints to potentially elucidate the differences between these two procedures.

Objective Coffee consumption can be expected to reduce mortality due to cardiovascular diseases and cancer. This study tested the hypothesis of an inverse association between coffee intake and all-cause mortality and mortality due to cancer, coronary heart disease, or stroke. Study design Prospective cohort study. Methods We analyzed data from the Jichi Medical School Cohort Study, Japan, enrolling 9946 subjects (men/women: 3870/6,076, age: 19–93 years) from 12 communities. A food frequency questionnaire assessing the subjects’ daily coffee consumption was used. Results During an average follow-up of 18.4 years, the total number of deaths was 2024, including 677 for cancer, 238 for coronary heart disease, and 244 for stroke. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality and cause-specific mortality due to cancer, coronary heart disease, and stroke. Overall, no significant association was shown between coffee consumption and all-cause mortality. In the cause-specific mortality analyses, stroke mortality was significantly lower in those who consumed 1–2 cups of coffee daily (HR [95% CI]: 0.63 [0.42–0.95]) than in those who do not consume coffee, and this association occurred only in men. Conclusion This study showed no significant association between coffee consumption and all-cause mortality. A U-shaped association between coffee consumption and stroke mortality with a 37% lower stroke mortality, only significant in men who consume 1–2 cups of coffee daily was observed. It is necessary to examine the possibility of intervention studies to reduce stroke mortality through coffee consumption

The long-term prognosis of those with a history of Kawasaki disease (KD) is still unknown.Using a permanent registry system in Japan (koseki), 6,576 persons with a history of KD were followed up. The average follow-up period was 30 years. The endpoint was death.With a 99.5% follow-up rate, 68 deaths (48 males and 20 females) were observed. The overall standardized mortality ratio, of which reference was vital statistics in Japan, was not elevated. However, the observation according to the presence or absence of cardiac sequelae showed that the standardized mortality ratio for those with cardiac sequelae significantly elevated. Nine persons, all of whom were males, died of KD (including those cases where KD was suspected), but all deaths occurred in individuals who were under 30 years of age.This study revealed the long-term prognosis for KD, but almost all participants were younger than 40 years. Continuing follow up of this cohort is required to clarify whether a history of KD relates to the development of atherosclerosis when participants become middle aged or older.

OBJECTIVES There are two major methods for local anesthesia by lidocaine before upper gastrointestinal endoscopy: simple spray and viscous solution. We aimed to assess the efficacy and safety by meta-analysis between these two methods. METHODS We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases through October 2019 to perform meta-analyses using random-effects models. The primary outcomes were participants' pain/discomfort, satisfaction, and anaphylactic shock. Three reviewers independently searched for articles, extracted data, and assessed the risk of bias. We evaluated the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study was registered in PROSPERO (CRD42020155611). RESULTS We included seven randomized controlled trials (2667 participants). The participants' pain/discomfort may be similar between the lidocaine spray and viscous solution [standardized mean difference 0.03, 95% confidence intervals (CI) -0.37 to 0.42; I2 = 93%; low certainty of evidence]. The lidocaine spray probably increased participants' satisfaction compared with the viscous solution (relative risk 1.22; 95% CI, 1.02 to 1.47; I2 = 47%; moderate certainty of evidence). No anaphylactic shock occurred in four studies (low certainty of evidence). Four studies had high risks of selection bias. CONCLUSION The use of lidocaine spray for local anesthesia provided better satisfaction scores than the viscous solution, and both methods have the same effect with regards to the control of discomfort and pain. Further studies in large multicenter randomized controlled trials with a pre-registration protocol are needed.

Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan-Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan–Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person‐years of follow‐up were included. The lifetime risk at the index‐age of 45 years for those with optimal risk factors (total cholesterol Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short‐term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

Resistant hypertension is an important cardiovascular risk factor. This analysis of the JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) data investigated the effects of uncontrolled resistant hypertension diagnosed using ambulatory blood pressure (BP) monitoring on the risk of heart failure (HF) and overall cardiovascular events. The JAMP study patients with hypertension and no HF history were included. They had true resistant hypertension (24-hour BP ≥130/80 mm Hg), pseudoresistant hypertension (24-hour BP P =0.012 and 2.24 [95% CI, 1.17–4.30]; P =0.015, respectively) and versus uncontrolled nonresistant hypertension (1.51 [1.03–2.20]; P =0.034 and 3.03 [1.58–5.83]; P Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000020377.

Background Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown. Methods A nationwide prospective cohort study of newly licensed physicians 2014–2018 (n = 2454) of the four major types of the programs—Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)—and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014–2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce. Results Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P P Conclusions Japan’s education policies to produce rural physicians are effective but the degree of effectiveness varies among the programs. Policymakers and medical educators should plan their future rural workforce policies with reference to the effectiveness and variations of these programs.

Aims/Introduction This randomized controlled trial aimed to determine whether frequent nutritional education improves the clinical parameters associated with the onset and progression of diabetic kidney disease in type 2 diabetes mellitus patients. Materials and Methods A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit, and the usual intervention group that received nutritional education once a year. The anthropometric parameters, blood pressure, blood chemistry, albuminuria, protein and salt intake, and prescribed medications of 87 patients who completed the 2‐year follow up were analyzed. Results In the intensive intervention group, body mass index and salt intake significantly decreased over the study period. Hemoglobin A1c levels and body fat percentage were significantly lower in the intensive intervention group than in the usual intervention group. At the end of the 2‐year intervention period, the intensive intervention group had significantly lower salt intake (8.1 vs 9.4 g/day) than the usual intervention group. A significant positive correlation was found between salt intake and albuminuria in the overall group and intensive intervention group (r = 0.26, P = 0.02, and r = 0.36, P = 0.02, respectively). The intensive intervention group had a significantly lower insulin use rate than the usual intervention group after the 2‐year intervention period (18% vs 42%). No differences were found in estimated glomerular filtration rate and albuminuria. Conclusion Intensive nutritional education is useful for alleviating the risk factors associated with the onset and progression of diabetic kidney disease.

Background: Increase of collagen in the extracellular matrix occurs with ageing. We investigated whether a collagen marker, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), was associated with risk of stroke. Methods and Results: In a nested case-control study of 953 subjects from the general population, we evaluated determinants of TIMP-1 level and stroke risk. Mean subject age was 65.7±8.6 years (53.0% men); TIMP-1 was 72.4±28.2 pg/mL in the control group and 75.3±30.9 pg/mL in the stroke group. The relationship between TIMP-1 quartile and stroke was J-curved. Subjects in the highest TIMP-1 quartile (≥89 ng/mL) had a significantly higher OR of stroke (59–72 ng/mL; OR, 1.90; 95% CI: 1.09–3.31, P=0.023) than those in the second TIMP-1 quartile, and this tended toward significance even after adjusting for confounding factors (P=0.059). Elevation of serum TIMP-1 became more marked after age 65 years. On multiple linear regression analysis, significant determinants of TIMP-1 were older age (B=0.21 per 1 year; 95% CI: 0.52–1.07, P

Isaku Kurotori,1 Katsutoshi Shioda,1 Takaaki Abe,1 Rika Kato,1 Shizukiyo Ishikawa,2 Shiro Suda1 1Department of Psychiatry; 2Department of Medical Education Center, Jichi Medical University, Tochigi, JapanCorrespondence: Katsutoshi ShiodaDepartment of Psychiatry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, JapanTel +81-285-58-7364Fax +81-285-44-6198Email kazs@jichi.ac.jpPurpose: To determine the clinical characteristics and course of severe avoidant/restrictive food intake disorder (ARFID) in hospitalized children and adolescents and compare them with those of patients with restricting-type anorexia nervosa (R-AN).Patients and methods: We conducted a retrospective chart review of inpatients diagnosed with ARFID or R-AN based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at Jichi Children’s Medical Center Tochigi between April 1, 2007 and March 31, 2017. We compared the characteristics of the ARFID and R-AN patients at admission, during hospitalization, and after discharge.Results: Both the ARFID (n=13) and R-AN (n=79) patients required hospitalization for their medically unstable state. The features of ARFID group included concern about the aversive consequences of eating and avoidance of eating due to sensory concerns. Significant differences were found at admission between ARFID and R-AN groups in age (10.7 vs 12.7 years), family history of mental disorders (46.2% vs 17.7%), comorbid developmental disorders (6 vs 3 cases), and the time from onset to admission (3.9 vs 6.3 months). The body weight status, % ideal body weight (%IBW), % expected body weight (%EBW)

Introduction: Those who are considered to be low risk in short term such as 10 year risk actually have high risk of cardiovascular disease for the remaining lifespan at younger age. Absolute risk of Lifetime risk (LTR) is more useful and understandable for lay audience compared with short term risk or relative risk. CKD (Chronic Kidney Disease) is global burden of cardiovascular disease (CVD) and hypertension is damaging complication of CKD for CVD. To date, there have been no reports of LTR with the outcome of CVD death based on CKD in Asian population. Hypothesis: We sought to estimate LTR of CVD death stratified by the status of CKD and hypertension. Methods: We used data from EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) which is designed to pool data from nationwide and regional cohort studies in Japan. Modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death at each index age starting from 40 years according to CKD stratified by Hypertension. Participants were classified into four groups, which were those without CKD and hypertension (CKD-/HT-), those with CKD but without hypertension (CKD+/HT-), those without CKD but with hypertension (CKD-/HT+), and those with both CKD and hypertension (CKD+/HT+). Results: A total of 44,582 participants from 8 cohorts was included in the analysis. Mean follow-up period was 14.9 years with 662,488 person years and total CVD death was 1,035 in men and 1,160 in women. The LTRs at the index age of 40 years increased in groups with CKD and/or HT as follows: 12.6% (95% confidence interval: 9.4 - 14.5%) in CKD-/HT- group, 20.6% (11.4 - 25.9%) in CKD+/HT- group, 23.2% (19.9 - 25.2%) in CKD-/HT+ group, and 27.9% (21.7 - 32.9%) in CKD+/HT+ group for men; 11.3%(8.9 - 13.2%), 17.4%(13.2 - 20.4%) , 17.8%(15.3 - 19.8%) , and 22.7%(19.5 - 25.2%) for women. Conclusions: We observed that complication of CKD and hypertension are collectively responsible for lifetime risk due to CVD death. Management of blood pressure from an early age is important to reduce CVD mortality in CKD patients.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): H20–Junkankitou [Seishuu]–Ippan–013; H23–Junkankitou [Seishuu]–Ippan–005; H26-Junkankitou [Seisaku]-Ippan-001; H29–Junkankitou–Ippan–003 and 20FA1002 OnBehalf EPOCH-JAPAN Introduction Absolute risk of Lifetime risk (LTR) is useful estimate for risk communication compared with short term risk or relative risk especially for young people. Proteinuria is leading cause of end-stage kidney disease (ESKD) and independent risk factor for cardiovascular disease (CVD). Although nonproteinuric renal disease is global burden of ESKD, it has been poorly focused. To date, there have been no reports of impact of proteinuria and low eGFR on LTR with the outcome of CVD death in Asian population. Purpose We aimed to estimate LTR of CVD death stratified by the status of proteinuria and low eGFR. Methods We used modified Kaplan-Meier approach to estimate the remaining lifetime risk of cardiovascular death based on EPOCH-JAPAN(Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) database. LTR was estimated at each index age starting from 40 years for those with proteinuria and without proteinuria stratified by low eGFR, which is defined as eGFR Results A total of 47,292 participants from 9 cohorts was included in the analysis. Mean follow-up period was 14.6 years with 690,463 person years and total CVD death was 1,075 in men and 1,193 in women. The LTRs at the index age of 40 years were as follows: 17.7% (95% confidence interval: 15.4 – 19.0%) in Proteinuria (-)/Low eGFR (-) group, 26.2% (20.2 – 31.1%) in Proteinuria (-)/low eGFR (+) group, 24.5% (15.1 – 29.3%) in Proteinuria (+) group for men; 15.3%(13.7 – 16.5%), 29.9%(14.7 – 46.8%) , 28.3%(19.4 – 34.7%) for women. Conclusions We observed that those without proteinuria with low eGFR have equivalently high LTR with those with proteinuria. These results indicate that even in the absence of proteinuria, low eGFR has high impact on LTR. Lifestyle modification from young age is necessary to prevent from renal dysfunction.

Background: Strategies to prevent the development and progression of chronic kidney disease (CKD) are important in clinical practice due to increased life expectancy. The present study investigated the prevalence of CKD as well as lipid profiles affecting CKD, especially triglyceride (TG) levels.Methods: In total, 5,169 subjects were eligible for a cross-sectional analysis of baseline data from the Jichi Medical School Cohort Study. We examined CKD subjects with an estimated glomerular filtration rate (eGFR) of 59 mL/min/1.73m2 or lower and independent factors associated with reductions in eGFR.Results: The prevalence of CKD was 17.7%. Age, systolic blood pressure, and hyperlipidemia were defined as related factors for CKD. The lowest, second, third, and highest quartile ranges of total cholesterol (TC) and TG were 0-166, 167-188, 189-212, and 213 mg/dL or higher and 0-71, 72-100, 101-148, and 149 mg/dL or higher, respectively. The odds ratio (OR) of Q2 to Q4 of TC relative to that of Q1 for CKD increased linearly (OR [95%CI]: Q2, 1.3 [1.0-1.7]; Q3, 1.38 [1.1-1.8]; Q4, 1.5 [1.4-2.4]). The ORs of Q2 and Q3 of TG for CKD did not increase, whereas that of Q4 did (OR [95% CI]: Q2, 0.95 [0.7-1.2]; Q3, 0.98 [0.8-1.2]; Q4, 1.21 [1.0-1.5]). Conclusion: Increases in TC and TG levels were both independently associated with CKD. The relationship with CKD became stronger as TC increased, and the TG had threshold was 149 mg/dL.

Background Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning. We designed a professional identity formation-oriented reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical year curriculum. Methods A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire. Results Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. Conclusions Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.

Background: Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning．We designed a professional identity formation-oriented mentoring format and tested effectiveness on raising self-regulated learning in a pre-clinical year curriculum. Methods: A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) received professional identity formation-oriented mentoring: Group A had three sessions in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire.Results: Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. Conclusions: Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.

BACKGROUND Several studies have described an association between hemoglobin concentration and stroke; however, the influence of hemoglobin on stroke incidence has not been fully revealed. Our objective was to elucidate the association between hemoglobin concentration and stroke incidence in Japanese community residents. METHODS In the present study, we collected the data of 12,490 subjects who were enrolled between April 1992 and July 1995 in the Jichi Medical School (JMS) Cohort Study. We excluded the subjects with a history of stroke. Hemoglobin concentrations were grouped in quartiles, and quartile 2 (Q2) was used as the reference category. A Cox proportional-hazards model was used to examine hazard ratios (HRs) and the stroke incidence rates with 95% confidence intervals (CIs). RESULTS During 10.8 years of follow-up, 409 participants (212 men and 197 women) experienced a new stroke, including 97 intracerebral hemorrhages, 259 cerebral infarctions, and 52 subarachnoid hemorrhages (SAH). In sex-specific hemoglobin quartiles, the multivariate-adjusted HR was statistically significantly higher in Q1 than in Q2, and a relationship similar to a J shape was observed between all strokes (HR in Q2 vs. Q1, 1.36; 95% CI, 1.02-1.83; Q3, 1.20; 95% CI, 0.87-1.64; and Q4, 1.16; 95% CI, 0.84-1.60). Furthermore, the analysis of stroke subtypes showed a statistically significantly higher multivariate-adjusted HR in Q1 than in Q2 for SAH (HR, 2.61; 95% CI, 1.08-6.27). CONCLUSIONS A low hemoglobin concentration was associated with an increased risk of stroke, which was strongly influenced by the incidence of SAH.

ObjectiveTo examine the association between polarity of atrial premature complexes (APCs) and stroke.DesignA prospective study.Setting and participantsA total of 11 092 participants in the Jichi Medical School cohort study were included after excluding patients with atrial fibrillation. We analysed stroke events in patients with (n=136) and without (n=10 956) APCs. With regard to polarity of APCs, patients were subcategorised into having (1) negative (n=39) or non-negative (n=97) P waves in augmented vector right (aVR), and (2) positive (n=28) or non-positive (n=108) P waves in augmented vector left (aVL).Outcome measuresThe primary endpoint was stroke.ResultsPatients with APCs were significantly older than those without APCs (64.1±9.2 vs 55.1±11.6 years, pConclusionsThe presence of APCs with non-negative P wave in aVR or non-positive P wave in aVL on 12-lead ECG was associated with a higher risk of incident stroke.

Background:Small dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the effect of age, gender, and menopausal status on sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.Methods:We examined the baseline cross-sectional data from the Jichi Medical School-II Cohort Study, including 5,208 participants (2,397 men and 2,811 women). To assess age-related trends, the sdLDL-C and sdLDL-C/LDL-C ratios were plotted against gender. We evaluated the effect of age and menopausal status using multiple linear regression analysis.Results:We observed that in men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked at 50–54 years, and then decreased. In women, we observed relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years, followed by a downward or pleated trend. The crossover of sdLDL-C levels for the genders occurred at 70–74 years, but we could not observe any sdLDL-C/LDL-C ratio crossover. Standardized sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year old men, premenopausal women, and postmenopausal women were 26.6, 22.7, and 27.4 mg/dL and 0.24, 0.15, and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (PConclusions:sdLDL-C and sdLDL-C/LDL-C ratios show different distributions by age, gender, and menopausal status with trends different from other lipids. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences, and menopausal status.

Background: Developing self-regulated learning (SRL) in a teacher-centered curriculum is challenging. Previous studies indicate professional identity formation (PIF), or the formation of self-identity with internalized values and norms of professionalism, might improve SRL．We designed a PIF-oriented education format for hybrid problem-based learning (PBL) and tested its effectiveness on SRL in a mixed research method.Methods: A randomized controlled crossover trial was conducted using 112 pre-clinical year students at Jichi Medical University. In the six one-day PBL sessions, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced PIF-oriented pre-PBL learning: Group A had three sessions in the first half, B in the second half. Between-group PIF and SRL levels were compared using Professional Identity Essay (PIE) and Motivated Strategies for Learning Questionnaire (MSLQ). A qualitative thematic analysis of potential reasons for PIF improvement was performed using the PIE description.Results: Two-level regression analyses showed moderate improvement of PIF stages over time (R2 = 0.069), regardless of intervention. PIF-oriented pre-PBL learning alone did not significantly improve PIE stages or MSLQ scores. Thematic analysis indicated that PIF-oriented pre-PBL learning helped students recognize realistic difficulties in clinical practice, and articulate professional image and values. However, encounters in extracurricular clinical settings had diverse and meaningful impacts on PIF.Conclusions: Limited effect of PIF-oriented pre-PBL learning on PIF and SRL indicate challenges in SRL-oriented education for pre-clinical year students within a teacher-centered hybrid PBL curriculum.

Background: Previous studies indicate professional identity formation (PIF), or formation of self-identity with internalized values and norms of professionalism, might influence self-regulated learning (SRL). However, it remains unclear whether or not PIF-oriented education can improve SRL in medical students. Methods: Rural community-based clinical clerkships (rCBCC) for Year 5 (Y5) students in Jichi Medical University (JMU) provide a learning environment where undergraduates will work in future with alumni directly mentoring them. To make rCBCC more PIF-oriented, we created a learning platform using Google Forms and a PIF-oriented teaching manual for mentors. These were designed to help undergraduates articulate future ‘self’ images as professionals, and have in-depth communication with mentors as role models pertaining to medical professionalism. Forty-one Y5 JMU students experienced PIF-oriented rCBCC, while 41 Y5 control subjects experienced the original format rCBCC. Changes in SRL between the two groups were compared using 15 categories of motivated strategies for learning questionnaire (MSLQ). We also explored how the PIF-oriented rCBCC changed their SRL by thematic analysis of questionnaire and interview data.Results: A moderate improvement of intrinsic goal orientation (p = 0.005, ε2 = 0.096) and a mild improvement of critical thinking (p = 0.041, ε2 = 0.051) were observed in the PIF-oriented rCBCC. Qualitative analysis revealed they started viewing ‘professional responsibility’ as self-study motivator. Awareness of ‘responsibility’ led to pursuit of authenticity and medical knowledge applicability, and fostered critical thinking about learning contents. They also began elaborating learning contents in line with processes. Conclusion: This is the first study showing some effects of PIF-oriented education on SRL improvement. Fostering PIF may be important for stimulating learners’ intrinsic SRL behaviors.

We aimed to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) concentration and the incident stroke subtypes. We enrolled 11 027 participants between the ages of 18 and 90 years without a history of stroke in 12 Japanese communities. Cox’s regression models were used for stroke subtypes, adjusted for traditional risk factors, according to the categories based on HDL-C concentrations: 1.04 to 1.55 mmol/L, ≥1.56 mmol/L, and

Supplemental material, 20191107supplementary_material_1 for High-Density Lipoprotein Cholesterol and Risk of Stroke Subtypes: Jichi Medical School Cohort Study by Jun Watanabe, Eiichi Kakehi, Kazuhiko Kotani, Kazunori Kayaba, Yosikazu Nakamura and Shizukiyo Ishikawa in Asia Pacific Journal of Public Health

Smoking is a risk factor for stroke. The relationship between smoking and the risk of different subtypes of stroke has not been fully elucidated. We investigated the relationship between smoking and the incidence of stroke in the Japanese population.This prospective, population-based cohort study included 11,324 participants (4447 men; 6877 women) from 12 districts in Japan, between April 1992 and July 1995. Participants were stratified according to smoking status (non-smoker [never smoked]/ex-smoker/current smoker). Male current smokers were further stratified according to the number of cigarettes smoked per day (1-14, 15-29, or ≥ 30). The non-smoking group was used as a reference. Cox proportional hazards analysis was used to determine the risk of stroke due to smoking.Four hundred and seventeen new stroke events (212 men; 205 women) were recorded during a mean follow-up of 10.7 years, including 95 intracerebral hemorrhages (48 men; 47 women), 267 cerebral infarctions (152 men; 115 women), and 54 subarachnoid hemorrhages (12 men; 42 women). In multivariable analysis, the hazard ratios (95% confidence intervals) for male current smokers (≥ 30 cigarettes/day) were 1.89 (1.08-3.31) and 3.41 (1.22-9.57) for all strokes and intracerebral hemorrhages, respectively; those for female current smokers were 2.78 (1.62-4.74), 3.14 (1.51-6.54), and 4.03 (1.64-9.93) for all strokes, cerebral infarctions, and subarachnoid hemorrhages, respectively.Smoking ≥ 30 cigarettes/day is a risk factor for stroke, especially intracerebral hemorrhage in men. Furthermore, smoking increases the risk of cerebral infarction and subarachnoid hemorrhage in women.

Objective: The aim of the present study was to investigate the clinical and nutritional factors influencing the renal function of the transplanted kidney during a one-year follow-up period after transplantation. Patients: The present prospective observational study included 52 patients who underwent kidney transplantation at Jichi Medical University Hospital from 2014 to 2016. Results: The serum creatinine (sCr) concentration at one month after transplantation was closely related to the concentration at 12 months. The recipients were divided into two groups based on the sCr concentration at one month after transplantation. Recipients with a sCr concentration greater than or equal to the median were classified into Group H, while those with concentrations that were less than the median were classified into Group L. A stepwise multiple regression analysis demonstrated that the salt intake in male recipients was an independent predictor of the renal function at 12 months (β = 0.663, p β = 0.618, p < 0.01). Moreover, in female recipients, the BMI and serum uric acid values in Group H were significantly higher than those in Group L. The BMI values of the female recipients in Group H were significantly higher than those in Group L at all times during the follow-up period (p < 0.01). Conclusion: The daily salt intake was independently associated with the renal function at one year after kidney transplantation in male recipients. In female recipients, the BMI was independently associated with the sCr concentration during the one-year follow-up period.

Previous studies have found the prevention paradox in the association between stroke events and a single specific risk factor, indicating that a population-based strategy may be more effective than a high-risk-based strategy for prevention. We tested the hypothesis that the prevention paradox does not apply when focusing on multiple potential risk factors simultaneously. The study cohort included 9051 individuals from Japan aged 40–89 years. The time-dependent Cox proportional-hazards models were used to identify the primary risk factor associated with stroke onset. We classified participants based on risk factors in two distinct ways: 1) classifying the high-risk group participants according to a single specific risk factor that had a large association with stroke in both sexes and all ages and 2) classifying the high-risk group participants according to 1–3 risk factor(s) including hypertension, hyperglycemia, and/or dyslipidemia. Then, we compared the proportions of the total number of participants who developed stroke in both groups to assess the prevention paradox. We found that hypertension was a primary risk factor for stroke incidence, regardless of sex and age. The percentage of patients with a single specific risk of and developed stroke was 46%–63%, while the percentage of patients with 1–3 risk factor(s) was 71–83%. This finding leads to the conclusion that the prevention paradox does not hold when multiple stroke risk factors were associated, suggesting that a high-risk-based strategy that focuses on patients with multiple risk factors may be more effective in preventing strokes.

Background Whereas high body mass index (BMI) is reportedly a risk factor for cardiovascular events in Western countries, low BMI has been reported as a risk factor for cardiovascular death in Asia, including Japan. Although subarachnoid hemorrhage (SAH) is a highly fatal disease and common cause of disability, few cohort studies have examined the associations between BMI and SAH in Japan. This study investigated the associations between BMI and incidence of SAH using prospective data from Japanese community residents. Methods Data were analyzed from 12,490 participants in the Jichi Medical School Cohort Study. Participants were categorized into 5 BMI groups: ≤18.5, 18.6-21.9, 22.0-24.9, 25.0-29.9, and ≥30.0 kg/m 2 . Multivariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard model with BMI of 22.0-24.9 kg/m 2 as the reference category. Results During the mean follow-up period of 10.8 years, 55 participants (13 men, 42 women) experienced SAH. BMI ≥30.0 kg/m 2 was associated with significantly higher risk for SAH (HR, 5.98; 95% CI, 2.25-15.87). BMI ≤18.5 kg/m 2 showed a nonsignificant tendency toward high risk of SAH (HR, 2.51; 95% CI, .81-7.79). Conclusions High BMI was a significant risk factor for SAH. Lower BMI showed a nonsignificant tendency toward higher risk of SAH. Our results suggest a J-shaped association between BMI and risk of SAH incidence.

Background High body mass index (BMI) has been reported as a risk factor for cardiovascular events in Western countries, while low BMI has been reported as a risk factor for cardiovascular death in Asian countries, including Japan. Although stroke is a major cause of death and disability in Japan, few cohort studies have examined the association between BMI and stroke incidence in Japan. This study aimed to examine the association between BMI and stroke incidence using prospective data from Japanese community residents. Methods Data were analyzed from 12,490 participants in the Jichi Medical School Cohort Study. Participants were categorized into five BMI groups: ≤18.5, 18.6–21.9, 22.0–24.9, 25.0–29.9, and ≥30.0 kg/m2. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. The group with a BMI of 22.0–24.9 kg/m2 was used as the reference category. Results During mean follow-up of 10.8 years, 395 participants (207 men and 188 women) experienced stroke, including 249 cerebral infarctions and 92 cerebral hemorrhages. Men with a BMI ≤18.5 kg/m2 (HR 2.11; 95% CI, 1.17–3.82) and women with a BMI ≥30.0 kg/m2 (HR 2.25; 95% CI, 1.28–5.08) were at significantly higher risk for all-stroke. Men with a BMI ≤18.5 kg/m2 were at significantly higher risk for cerebral infarction (HR 2.15; 95% CI, 1.07–4.33). Conclusions The association between BMI and stroke incidence observed in this population was different than those previously reported: low BMI was a risk factor for all-stroke and cerebral infarction in men, while high BMI was a risk factor for all-stroke in women., Highlights • The association of body mass index (BMI) with stroke remains controversial in Japan. • Our large cohort study examined the association of interest in a Japanese population. • Low BMI increased the risk of all-stroke and cerebral infarction incidence in men. • In contrast, high BMI increased the risk of all-stroke incidence in women.

Prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Tsuda et al. show that Crhr2 activation causes cardiac dysfunction and suggest Crhr2 blockade is a promising therapeutic strategy for chronic heart failure., Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.

Lifetime risk (LTR) provides an absolute risk assessment during the remainder of one’s life. Few studies have focused on the LTRs of stroke and coronary heart disease (CHD), categorized by fine blood pressure in Asian populations. We aimed to assess it using a large database of a meta-analysis with the individual participant data. The present meta-analysis included 107 737 Japanese (42.4% men; mean age, 55.1 years) from 13 cohorts. During the mean follow-up of 15.2±5.3 years (1 559 136 person-years), 1922 died from stroke and 913 from CHD. We estimated risks after adjusting for competing risk of death other than the outcome of interest. The 10-year risk of stroke and CHD deaths at index age of 35 years was ≤1.9% and ≤0.3%, respectively. The LTRs of stroke death at the index age of 35 years (men/women) were 6.1%/4.8% for optimal, 5.7%/6.3% for normal, and 6.6%/6.0% for high-normal blood pressure groups, and 9.1%/7.9% for grade 1, 14.5%/10.3% for grade 2, and 14.6%/14.3% for grade 3 hypertension groups. The LTRs of CHD death similarly elevated with an increase in blood pressure but were lower (≤7.2%) than those of stroke death. In conclusion, blood pressure was clearly associated with an elevated LTR of stroke or CHD death, although the LTR of CHD death was one-half of that of stroke death in an Asian population. These results would help young people with hypertension to adopt a healthy lifestyle or start antihypertensive therapy early.

Japan is an aging society, and the incidence of diseases related to aging, such as pneumonia, heart failure, vertebral compression fracture (VCF), is increasing. Prolonged hospital stays are becoming a serious social problem, leading to elevated medical expenses. Thus, shortening the period of hospitalization is important. This study aimed to reveal determinants associated with prolonged hospital stays for patients with VCF. Our institution is the primary hospital in a rural area in the Kanto region of Japan. Altogether, 110 patients with a VCF, aged 65 years or older, including 79 women, were divided into two groups according to the average hospital stay period of 28 days: the long-stay group (mean stay 40.0 ± 11.6 days, n = 39) and the short-stay group (mean stay 20.6 ± 4.4 days, n = 71). Notably, the short-stay group included 55 women. Multivariate logistic regression analyses in male showed no variates significantly associated with prolonged hospitalization. By contrast, multivariate logistic regression analyses in female showed requiring emergency transportation to hospital was significantly associated with prolonged hospitalization [odds ratio 7.69, 95% confidence interval 1.13-52.29, P = 0.04]. In conclusion, this study implies that patients with better levels of activities of daily living are able to walk alone sooner and are easily discharged. Furthermore, the patient requiring emergency transportation might be in a poor social living environment, such as living alone. These results may give us a good opportunity to re-consider fundamental problems surrounding the elderly.

Additional file 1: Table S1. Multivariate analysis of cancer mortality with metabolic syndrome by sex, excluding participants

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Background Due to ethic differences in its serum levels, clinical applicability of high-sensitivity C-reactive protein (hsCRP) to the primary prevention of atherosclerotic events has not completely been established in Japanese people whose hsCRP levels are lower than in Western people. This study investigated the relationship between hsCRP and myocardial infarction (MI) in general Japanese people. Methods In relation to hsCRP, the incidence of MI was determined in a multiregional population-based prospective cohort study (n = 6,637; mean age 54.9 years; 2,513 men/4,124 women). Results Fifty-six cases of MI were confirmed during a follow-up period of 10.7 years. The cut-off levels of hsCRP between the highest quartile (fourth quartile) and the other quartiles combined were 0.368 mg/l in men and 0.279 mg/l in women. The hazard ratio (HR) of the highest quartile for MI was significantly greater than that of the other quartiles combined (multivariate-adjusted HR: 2.07, 95% confidence interval: 1.03–4.15) in men, but not in women (1.03, 0.35–2.21). Conclusions In this population, serum hsCRP measurement predicted MI in men, but not in women. Under the low hsCRP level, a method of applicability of hsCRP to a risk assessment for preventing MI among Japanese people should be further explored.

Dietary salt intake has been reported to be associated with cardiovascular disease (CVD). However, there were few studies that assessed the relationship of salt preference with CVD. We examined the association between salt preference and the incidence of CVD and its subtypes in a Japanese general population. Based on the prospective Jichi Medical School Cohort Study, data were analyzed from 11,394 eligible participants. A baseline survey of the preference for salt was obtained by questionnaire and health examinations from April 1992 through July 1995 in 12 communities in Japan. The participants were followed up until December 2005 (mean follow-up period, 10.7 ± 2.4 years). Subjects were divided into three categories according to their preference for salt: favor, so-so, and disfavor. A Cox proportional hazards model was used to calculate hazard ratios (HRs) of the incidence of CVD according to the preference categories. We observed 485 cardiovascular events (258 in men and 227 in women). Among the men, the multivariable adjusted HRs for incidence of myocardial infarction and subarachnoid hemorrhage for favor versus so-so salt preference were 0.34 (95% confidence interval, 0.17 - 0.71) and 7.10 (0.88 - 56.84), respectively. Among the women, age-adjusted HRs for the incidence of CVD, total stroke, cerebral hemorrhage, and cerebral infarction for the favor preference were 1.41 (1.02 - 1.95), 1.36 (0.97 - 1.91), 1.79 (0.87 - 3.71), and 1.40 (0.89 - 2.19), respectively. The data indicated that preference for salt may be associated with an increase in the incidence of CVD in women.

Background: Previous studies on the association between coffee consumption and subarachnoid hemorrhage (SAH) have provided inconsistent results. We examine the risk of SAH from coffee consumption in a Japanese population. Methods: Our analyses were based on the Jichi Medical School Cohort Study, a large-scale population-based prospective cohort study. A total of 9941 participants (3868 men and 6073 women; mean age 55 years) with no history of cardiovascular disease or carcinoma were examined. Participants were asked to choose one of five options to indicate their daily coffee consumption: none, less than 1 cup a day, 1–2 cups a day, 3–4 cups a day, or 5 or more cups a day. The incidence of SAH was assessed independently by a diagnostic committee. Cox proportional hazards models were used to calculate hazard ratios (HRs) and their 95% confidence intervals (CI) after adjustment for age and sex (HR1) and for additional potential confounders (HR2). Results: During 10.7 years of follow-up, SAH occurred in 47 participants. When compared with the participants who consumed less than 1 cup of coffee a day, the HR of SAH was significantly higher in the group who consumed 5 or more cups a day in both models (HR1 4.49; 95% CI, 1.44–14.00; HR2 3.79; 95% CI, 1.19–12.05). Conclusions: The present community-based cohort study showed that heavy coffee consumption was associated with an increased incidence of SAH after adjusting for age, sex, and multiple potential cardiovascular confounders.

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "

Background Minor ST-T changes are frequently observed on the electrocardiogram (ECG), but the risk of stroke associated with such changes is unclear.Methods and Results:In 10,642 subjects from the Japanese general population, we evaluated minor and major ST-T changes (major ST depression ≥0.1 mV) on ECGs obtained at annual health examinations. At baseline, minor ST-T changes were found in 10.7% of the subjects and 0.5% had major ST-T changes. Minor ST-T changes were associated with older age, female gender, higher systolic blood pressure, presence of hyperlipidemia, and use of antihypertensive medication. There were 375 stroke events during the follow-up period (128.7±28.1 months). In all subjects, minor ST-T changes (HR, 2.10; 95% CI: 1.57-2.81) and major ST-T changes (HR, 8.64; 95% CI: 4.44-16.82) were associated with an increased risk of stroke, but the stroke risk associated with minor ST-T changes had borderline significance after adjustment for conventional risk factors (P=0.055). In subgroup analysis, the risk of stroke was significantly associated with minor ST-T changes in subjects who had hyperlipidemia (HR, 1.75; 95% CI: 1.15-2.67) compared to those without hyperlipidemia (HR, 1.01; 95% CI: 0.64-1.59; P for interaction=0.016), even after adjustment for ECG-diagnosed left ventricular hypertrophy. Conclusions Minor ST-T changes were particularly associated with a higher risk of stroke in subjects with hyperlipidemia and this association was independent of electrocardiographic left ventricular hypertrophy.