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Background Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in one second (FEV1) decline. Methods Participants consisted of a resident population (n=2,612, aged 67.7) with FEV1 measurement in 2012-2014 and 2018-2019, and a worksite population (n=722, aged 49.3) without FEV1 data. Participants were categorized as never, past and combustible cigarette-only smokers, and HTP-only and dual users. The association between smoking group and the change in smoking consumption for 5.6 years was examined. Differences in annual FEV1 change between smoking groups were examined in the resident population. Results Prevalence of HTP-only and dual users in 2018-2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV1 decline in dual users tended to be greater than that in cigarette-only smokers (16 mL/yr [95% CI: -34, 2] after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV1 decline as cigarette-only smokers. Conclusions HTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV1 decline. Tobacco policy should consider dual use as high-risk.

Aim This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75-31.50) for men and 4.44 (95% CI 1.14-17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Patients or Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results (odds ratio [OR], 5.475; 95% confidence interval [CI], 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively). No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Aims The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness. Methods In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35-74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: "Category I (Low risk)," "Category II (Middle risk)," and "Category III (High risk)." Results The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61-5.43) and 7.33 (4.03-13.3) for males and 3.99 (2.55-6.24) and 3.34 (2.16-5.16) for females, respectively. Conclusions The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.

Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEVParticipants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEVPrevalence of HTP-only and dual users in 2018-2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEVHTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV

Background Heated tobacco product (HTP) users are rapidly increasing in Japan since 2014. Controlling HTPs is now one of the most urgent issues. We aimed to clarify the change of smoking habits by introducing and spreading HTPs. Methods We conducted the survey of HTP use in the participants of the Tsuruoka Metabolomics Cohort Study, a prospective cohort including 11,002 participants aged 40-74 in Japan. All data were obtained in the follow-up (2018-2019) and baseline (2012-2013) survey. Smoking habits were categorized to five groups according to follow-up survey; never smokers (NS), past smokers (PS), cigarette only smokers (CS), HTP only smokers (HS) and dual smokers (DS). Linear regression analysis was performed to examine the association between smoking habits and change of number of smoking tobacco products during follow-up. Results Prevalence of HTP user was 12.4% in 40-59 years of age and 1.8% in 60-79 for male, and 1.7% in 40-59 and 0% in 60-79 for female. Dual smokers accounted for 34.9% of all HTP users. Change of smoking number during follow-up (5.7±0.8 years) was +3.11 (95%CI: 1.17, 5.07) in DS and -1.09 (-2.70, 0.53) in HS compared with CS, after adjusted for age, sex and smoking number at baseline. Conclusions HTPs smoking including dual smoking was getting popular in Japan. Shift to HTPs was unlikely to affect the number of smoking tobacco, but dual smokers tended to smoke more than at baseline. Key messages Dual smokers of cigarettes and HTPs tended to smoke more than before introducing and spreading HTPs.

BACKGROUND:The trend of association between overweight and high serum total cholesterol (TC)among the elderly is unclear. In addition, there is little evidence of risk of underweightfor high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data., METHODS:Data of the National Survey on Circulatory Disorders and National Health and NutritionSurvey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was definedas 220 mg/dL and above. For participants aged ≥50 years, sex-specific odds ratios (ORs)of overweight or underweight compared with normal body mass index participants forhigh TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia., RESULTS:A total of 5,014, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980,1990, 2000, and 2010, respectively. Although overweight was positively and significantlyassociated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83-3.24 and 0.92; 95% CI, 0.66-1.27 among men and 1.43; 95% CI, 1.18-1.72 and 1.08; 95% CI, 0.81-1.44 among women, respectively). While underweight was inversely and significantlyassociated with high TC in 1980, the association also gradually weakened among women(ORs in 1980 and 2010 were 0.28; 95% CI, 0.12-0.60 and 0.37; 95% CI, 0.10-1.28 among men and 0.39; 95% CI, 0.26-0.57 and 0.96; 95% CI, 0.58-1.57 among women,respectively)., CONCLUSIONS:These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.

Background Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. Methods Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. Results The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93-0.96) and 0.97 (95% CI, 0.96-0.98) for antihypertensive medications, 0.94 (95% CI, 0.91-0.97) and 0.98 (95% CI, 0.98-0.99) for diabetes medications, and 0.84 (95% CI, 0.82-0.87) and 0.98 (95% CI, 0.97-0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. Conclusions In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.

Objective Several studies have suggested that high dietary Na/K ratio and body mass index (BMI) increase the prevalence of hypertension. However, there have been a few reports on the combination of these two factors and their relationship with hypertension. This study aimed to examine the association of the combined estimated 24-h urinary Na/K ratio (24h-u-Na/K) (high or low) and BMI (high or low) with the risk of high blood pressure.Method We performed a cross-sectional study involving 1,112 participants (340 men and 772 women) of the Kobe Orthopedic and Biomedical Epidemiological study (KOBE study) who had no cardiovascular diseases or current anti-hypertensive medications. Sex-specific analyses were performed. The 24h-u-Na/K ratio was calculated from an estimation formula using collected spot urine. Participants were divided into four groups based on their 24h-u-Na/K ratio (low or high) and BMI (low or high), with the cutoff points being the median and 25 kg/m

ObjectivesTo date, the association between accumulated unhealthy behaviours and insomnia in individuals stratified according to the presence or absence of major cardiovascular risk factors is unclear. This study aimed to examine the effect of accumulated unhealthy behaviours on insomnia in Japanese dwellers.DesignCross-sectional study.SettingBaseline data between April 2012 and March 2015.ParticipantsOur study used cross-sectional data among Japanese aged 35–74 years in a rural community (N=9565), the attendees of annual municipal or work site health check-up programmes.Main outcome measuresInsomnia was assessed by Athens Insomnia Scale, which was set at 6 points and greater; other scales were given. Participants were categorised into three groups by their number of unhealthy behaviours (no exercise habit, smoking, alcohol drinking, skipping breakfast and obesity): 0–1, 2–3, 4 or more. The association between accumulated unhealthy behaviours and insomnia was estimated by logistic regression analysis. Further analysis was done after stratification of cardiovascular risk factors assessed by anthropometrics and clinical biochemistry measurements.ResultsThe overall prevalence of insomnia was 13.3% for men and 19.3% for women. Men with unhealthy behaviour factors were more likely to have insomnia after adjusting for potential confounders, compared with the least unhealthy group (trend p=0.013). Women with four or more unhealthy behaviour factors were more likely to have insomnia, compared with the lowest groups (OR 1.175, 95% CI 1.077 to 1.282). Insomnia has an association with the unhealthy behaviours among men without cardiovascular risk factors (lowest groups: OR 1.133, 95% CI 1.037 to 1.238, trend p=0.026). Women without hypertension were more likely to have suspected insomnia, compared with the lowest group (OR 1.215, 95% CI 1.101 to 1.341).ConclusionThe results showed accumulated unhealthy behaviours were associated with increased risk of insomnia in Japanese dwellers. For healthy population without cardiovascular risk factors, unhealthy behaviours should be considered as background conditions for insomnia.

Background : Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. Methods : The participants were 1193 female residents aged 40-60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. Results : Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. Conclusion : Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

Objective To explore health-related and socioeconomic factors that can predict future deterioration in Psychological Distress Scale (K6) scores.Method We conducted a baseline (2010, 2011) self-administered questionnaire survey of the Kobe Orthopedic and Biomedical Epidemiological study (KOBE study) involving 1,117 participants who had no previous history of cancer or cardiovascular diseases and were not under treatment for hypertension, diabetes, or dyslipidemia. We used the Japanese K6 as an indicator of stress and defined K6≧5 points as a high-stress group and K65 points as a low-stress group. A four-year follow-up survey (2014, 2015) was conducted on 1,004 people (follow-up rate of 90%). We excluded 39 participants with missing values, and 185 people whose K6 score was higher than 5 points at baseline. A final total of 780 participants' scores were examined for: gender, age, living situation, physical activity level, average sleep time, as well as the K6 score, the Japanese Hearing Handicap Inventory for Elderly (HHIE-S), and the Japanese Oswestry Disability Index (ODI). We conducted a logistic regression analysis using K6≧5 points at the four-year follow-up survey as the dependent variable and each factor at the baseline survey as the independent variable.Results Of the 780 subjects analyzed, 132 (16.9%) were highly stressed (K6≧5 points) at the four-year follow-up point. A logistic regression analysis found age (40s/70s) (odds ratio 3.38, 95% confidence interval 1.45-7.86), living situation (single/living together) (odds ratio 1.98, 95% confidence interval 1.07-3.68), and ODI scores (every 1%) (odds ratio 1.05, 95% confidence interval 1.01-1.09), to all be significantly associated with high stress.Conclusion This study suggests that age, living situation, and ODI scores are related to future stress.

Aim Fatty liver is associated with the development of diabetes. However, to our knowledge, no study has examined the relationship between the fatty liver index (FLI), calculated scores of hepatic steatosis, and the development of diabetes among individuals without impaired fasting glucose (IFG). We aimed to examine whether FLI predicts the development of diabetes in individuals with and without IFG in a Japanese general population. Methods We selected 1498 men and 2941 women who participated in Specific Health Checkups in Japan. We divided all participants into six groups according to tertiles of FLI (low, moderate, and high) and the presence or absence of IFG, by sex. We calculated hazard ratios for incident diabetes for each group using a Cox proportional hazard model, adjusting for potential confounders. Results During a mean follow-up period of 3.0 years, 176 cases of diabetes in men and 320 cases in women were identified. Compared with the low FLI group without IFG, the high FLI group without IFG was significantly associated with incident diabetes in both men (hazard ratio, 1.90; 95% confidence interval, 1.08-3.36) and women (hazard ratio, 1.72; 95% confidence interval, 1.18-2.51). All IFG groups were significantly associated with incident diabetes regardless of FLI levels. Conclusions Our results showed that FLI is associated with the development of diabetes regardless of sex and the presence or absence of IFG, and that it may be a useful predictor of future risk of incident diabetes even in individuals without IFG.

The plasma homocysteine concentration is a good indicator of various diseases such as cardiovascular disease, stroke, and dementia. This study examined the relationship between plasma homocysteine concentrations and dietary habits in a population of elderly Japanese people from the Amami Islands. Data from 1131 participants collected during a baseline survey for the Japan Multi-institutional Collaborative Cohort study, which is a prospective cohort study, were used. Information on dietary habits was collected using a food frequency questionnaire. The plasma homocysteine concentration was associated with age in women only. Smoking in men and menopause were significantly associated with homocysteine concentrations. Analysis of blood biochemical data showed that estimate of glomerular filtration rate negatively correlated with plasma homocysteine in women (R = −0.91, p < 0.001) and men (R = −0.49, p < 0.001). There was no common food associated with homocysteine concentrations among the groups, but in each group, some food types were associated with homocysteine concentrations. In men, Chinese tea was a common factor showing a negative correlation with homocysteine concentrations. Natto showed a negative correlation with homocysteine concentrations in non-smoking men (β = −0.11, p < 0.05) and premenopausal women (β = −0.20, p < 0.01). Eggs (β = −0.21, p < 0.01) and food processed from fish eggs (β = −0.21, p < 0.01) negatively correlated with homocysteine concentrations in smoking men. Miso soup (β = −0.13, p < 0.01) and yoghurt (β = −0.10, p < 0.05) negatively correlated with homocysteine concentrations in postmenopausal women. Consumption of folate-rich food did not necessarily correlate with a low plasma Hcy concentration.

Background An increased risk of total death owing to human T-lymphotropic virus type-I (HTLV-I) infection has been reported. However, its etiology and protective factors are unclear. Various studies reported fluctuations in immune-inflammatory status among HTLV-I carriers. We conducted a matched cohort study among the general population in an HTLV-I-endemic region of Japan to investigate the interaction between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases. Method We selected 2180 sub-cohort subjects aged 35–69 years from the cohort population, after matching for age, sex, and region with HTLV-I seropositives. They were followed up for a maximum of 10 years. Inflammatory gene polymorphisms were selected from TNF-α, IL-10, and NF-κB1. A Cox proportional hazard model was used to estimate the hazard ratio (HR) and the interaction between gene polymorphisms and HTLV-I for risk of total death and incidence of cancer and atherosclerosis-related diseases. Results HTLV-I seropositivity rate was 6.4% in the cohort population. The interaction between TNF-α 1031T/C and HTLV-I for atherosclerosis-related disease incidence was statistically significant (p = 0.020). No significant interaction was observed between IL-10 819T/C or NF-κB1 94ATTG ins/del and HTLV-I. An increased HR for total death was observed in the Amami island region, after adjustment of various factors with gene polymorphisms (HR 3.03; 95% confidence interval, 1.18–7.77). Conclusion The present study found the interaction between TNF-α 1031T/C and HTLV-I to be a risk factor for atherosclerosis-related disease. Further follow-up is warranted to investigate protective factors against developing diseases among susceptible HTLV-I carriers., Highlights • We observed death and incidence risk with HTLV-I and SNPs in a matched cohort study. • An increased risk for total death with HTLV-I was observed in the island region. • Inflammatory SNP interacted with HTLV-I for atherosclerosis-related disease risk.

Background and aim Few studies have clarified the seasonal and age-related change of serum osmolarity and water intake, which is thought to be associated with heat stroke and ischemic stroke. We investigated the association between them in a healthy population. Methods We conducted a cross-sectional study using database from Kobe Orthopedic and Biomedical Epidemiologic (KOBE) Study. Among 1138 healthy Japanese participants in the baseline survey, 1010 (women 704 and men 306) participants were eligible for the present study. Daily non-alcohol drink (NAD) intake was estimated according to food frequency questionnaire. Alcohol beverage and water in the meal or soup were excluded from the counting. Serum osmolarity (Osm/L) was calculated by Worthley’s formula: 2 (serum sodium (mEq/L)) + (blood urea nitrogen (mg/dL))/2.8 + (glucose (mg/dL))/18. The seasons the surveys were conducted were categorized into 4 groups, March-May (Spring), June-August (Summer), September-November (Autumn), and December-February (Winter). The association between serum osmolarity and daily NAD intake was analyzed using linear regression models. Results The seasonal change was observed in the serum osmolarity and daily NAD intake; serum osmolarity increased in spring and summer and daily NAD intake increased in summer. The serum osmolarity increased by aging in any seasons, while daily water intake didn’t. There was no significant association observed between serum osmolarity and the daily NAD intake, even after adjusting for sex, age, and season. Conclusions Serum osmolarity showed seasonal and age-related changes, but the serum osmolarity in subjects who had the daily habit of high NAD intake was not necessarily low. Key messages Serum osmolarity increased by aging and in spring and summer. Serum osmolarity was not associated with non-alcohol drink intake.

Introduction Some studies reported that health behaviors and lifestyles are related to sleep disorder; obesity, drinking, smoking and lack of physical exercise are risk factors for insomnia. However, it’s unclear the association between accumulated unhealthy behaviors and insomnia in consideration of lifestyle-related diseases. Therefore, this study was to examine the effect of accumulated unhealthy behaviors on insomnia in a Japanese community population. Methods The subjects included 1,1002 participants aged 35–74 years. Sleep quality was assessed by the Athens Insomnia Scale. Unhealthy behaviors were classified into smoking, drinking, no habit of exercising, obesity, and skipping breakfast. We examined the impact of unhealthy behaviors accumulation, which was stratified into three categories, i.e., 0-1,2-3,4 or more, on insomnia. The association between accumulated unhealthy behaviors and insomnia was estimated by logistic regression analysis. Further analysis after stratification by lifestyle-related diseases was also performed. Results The overall prevalence of insomnia was 14.6% for men and19.3% for women. Men with unhealthy behaviors were more likely to have insomnia after adjusting for potential confounders, compared with the least unhealthy groups (trend p=0.017). Women with 4 or more unhealthy behavior factors were more likely to have the suspected insomnia, compared with the lowest groups (ORs 1.176 95% CI 1.079–1.282). Then, we analyzed to stratify by lifestyle-related disease. Insomnia has an association with unhealthy behaviors among men with the absence of diabetes (trend p=0.015) and dyslipidemia (trend p=0.032). Women without hypertension were more likely to have the suspected insomnia, compared with the lowest groups (ORs 1.215 95% CI 1.102–1.340), but the odd for those with the hypertension was 1.031(95%CI 0.855–1.243). Conclusion Accumulated unhealthy behaviors were associated with increased rates of insomnia in the Japanese community population. According to stratification by lifestyle-related disease, men showed the associations by the presence or absence of diabetes. Women showed the associations by the absence of hypertension. These associations were nearly similar regardless of the presence or absence of lifestyle-related disease. Support (if any) This research was supported by research funds from the Yamagata Prefectural Government and the city of Tsuruoka and the Grant-in-Aid for Scientific Research (JP24390168, JP15H04778 and JP19K19441) from the Japan Society for the Promotion of Science.

Food intake biomarkers can be critical tools that can be used to objectively assess dietary exposure for both epidemiological and clinical nutrition studies. While an accurate estimation of food intake is essential to unravel associations between the intake and specific health conditions, random and systematic errors affect self-reported assessments. This study aimed to clarify how habitual food intake influences the circulating plasma metabolome in a free-living Japanese regional population and to identify potential food intake biomarkers. To achieve this aim, we conducted a cross-sectional analysis as part of a large cohort study. From a baseline survey of the Tsuruoka Metabolome Cohort Study, 7,012 eligible male and female participants aged 40-69 years were chosen for this study. All data on patients' health status and dietary intake were assessed via a food frequency questionnaire, and plasma samples were obtained during an annual physical examination. Ninety-four charged plasma metabolites were measured using capillary electrophoresis mass spectrometry, by a non-targeted approach. Statistical analysis was performed using partial-least-square regression. A total of 21 plasma metabolites were likely to be associated with long-term food intake of nine food groups. In particular, the influential compounds in each food group were hydroxyproline for meat, trimethylamine-N-oxide for fish, choline for eggs, galactarate for dairy, cystine and betaine for soy products, threonate and galactarate for carotenoid-rich vegetables, proline betaine for fruits, quinate and trigonelline for coffee, and pipecolate for alcohol, and these were considered as prominent food intake markers in Japanese eating habits. A set of circulating plasma metabolites was identified as potential food intake biomarkers in the Japanese community-dwelling population. These results will open the way for the application of new reliable dietary assessment tools not by self-reported measurements but through objective quantification of biofluids.

Background Studies have shown significant associations of chronic kidney disease (CKD) and diabetes mellitus (DM) with cardiovascular disease (CVD) mortality. The impact on the general population is an important public health issue. However, the population attributable fraction (PAF) of CVD because of CKD and/or DM in a general population is uncertain. Methods We followed 7229 participants (age: ≥30 years) with no history of CVD in a Japanese community. We divided participants into four categories according to CKD and/or DM and calculated hazard ratios (HRs) of CVD mortality for each category using a Cox proportional hazards model adjusted for age, dyslipidemia, smoking and alcohol consumption. In addition, PAFs of CVD were estimated among populations with CKD and/or DM. Results During 20-year follow-up, 488 participants died. HRs for CVD were 1.63 [95% confidence interval (CI): 1.16-2.30] with DM only, 1.42 (95% CI: 1.08-1.86) with CKD only and 2.37 (95% CI: 1.40-4.01) with CKD + DM. In men, the corresponding HRs for CVD were 1.88 (95% CI: 1.19-2.97), 1.71 (95% CI: 1.15-2.56) and 3.26 (95% CI: 1.69-6.30), respectively; the corresponding PAFs of CVD were 4.1%, 5.1% and 2.9%, respectively. PAFs for CVD among women were lower than those in men, 1.6% for DM only, 2.0% for CKD only and 0.7% for CKD + DM. Conclusions PAFs of CVD mortality due to CKD and/or DM were not so high in past 20 years; however, they might increase in the future because of recent increase in prevalence of these in Japanese population.

AIM The Japan Atherosclerosis Society (JAS) Guidelines for Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases for Japanese 2012 version have set a non-high-density lipoprotein cholesterol (non-HDL-C)-management target of low-density lipoprotein cholesterol (LDL-C) ＋30 mg/dL. However, the actual difference between non-HDL-C and LDL-C is not clear. Therefore, we evaluated its joint distribution and assessed the validity of this criterion in the general Japanese population. METHODS We used baseline cross-sectional data of 4,110 participants from two studies; the KOBE Study (n=1,108) and the Tsuruoka Metabolomic Cohort Study (n=3,002). To evaluate whether the difference between LDL-C and non-HDL-C in the general population match that of the current guidelines, we classified LDL-C levels into four groups according to the JAS Guideline and evaluated its agreement with the corresponding non-HDL-C group. Analysis was also done using six groups (the previous four groups plus the upper and lower cut-off values). RESULTS The mean difference (mg/dL) between the non-HDL-C and LDL-C (for the KOBE Study and Tsuruoka Metabolomic Cohort Study, respectively) was 19.6 and 24.1 (p

The effect of the sodium-to-potassium ratio (Na/K) on renal function within the clinically normal range of renal function are limited. We investigated the effects of an estimated 24 h urinary Na/K (e24hUNa/K) on a 6-year renal function decline among 927 urban Japanese community dwellers with no history of cardiovascular diseases and medication for hypertension, diabetes, or dyslipidemia. We partitioned the subjects into quartiles according to the e24hUNa/K. The estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD/EPI) formula and renal function decline was defined as an absolute value at or above the third quartile of the eGFR decline rate. A multivariable logistic regression model was used for estimation. Compared with the first quartile of the e24hUNa/K, multivariable-adjusted odds ratios (ORs) for eGFR decline in the second, third, and fourth quartiles were 0.96 (95% confidence interval: 0.61&ndash, 1.51), 1.06 (0.67&ndash, 1.66), and 1.65 (1.06&ndash, 2.57), respectively. These results were similar when the simple spot urine Na/K ratio was used in place of the e24hUNa/K. Apparently healthy urban residents with an almost within normal range mean baseline eGFR and high e24hUNa/K ratios had an increased risk for a future decline in renal function. Reducing the Na/K ratio may be important in the prevention of chronic kidney disease in its early stage.

Individuals with an inactive acetaldehyde dehydrogenase 2 have an. elevated level of serum acetaldehyde after drinking alcohol, and this may cause an alcohol flushing response with symptoms such as facial flushing, tachycardia, headache, and nausea. Recent studies have suggested that the flushing response influences the association between alcohol consumption and various health-related outcomes. In the present study, we investigated the impact of the flushing response on the relationship between alcohol consumption and serum y -GTP levels in Japanese drinkers. We conducted a cross-sectional study of 521 Japanese drinkers (260 men and 261 'vomen) to examine the impact of the alcohol flushing response on the relationship between alcohol consumption and serum y -GTP levels. The subjects were divided into three groups according to the amount .of daily alcohol consumption. (low,20 g; moderate, 20-39 g;. and high,40 g). Multiple adjustments were performed with linear regression models to examine the association between daily alcohol consumption and serum y-GTP levels, adjusting for potential con- founders including the flushing response. We found that the proportion of flushers was significantly lower in the high alcohol consumption group than in the low consumption group. The results of a multivariable analysis showed that,serum y -GTP levels were significantly higher in the moderate and high consumption groups than in the low consumption group after. adjusting for all potential confounders other than the flushing response. In addition, the association between serum y -GTP levels and alcohol consumption was unchanged after adjusting for the presence of the flushing response. In conclusion, serum y -GTP levels increased with increasing alcohol-consumption regardless of the flushing response. Screening for heavy drinkers using serum y-GTP levels was very important to prevent alcohol-related diseases or health problems in health examination.

Background Although several epidemiological studies have suggested that high serum uric acid (SUA) levels are related to a decline in kidney function, only a few studies have investigated using cystatin C to calculate estimated glomerular filtration rate (eGFR). We aimed to clarify the relationship between SUA levels and kidney function assessed by cystatin C in a Japanese general community population without chronic kidney disease (CKD). Methods We conducted a community-based cross-sectional study that included 1086 healthy participants, aged 40–74 years, without CKD and not undergoing treatment of hyperuricemia, who had participated in the baseline survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. The preconditions for participation in this study were no past histories of cardiovascular disease or cancer, and not undergoing treatment for diabetes, hypertension, or dyslipidemia. We classified the participants into quartiles stratified by sex according to their SUA level and then examined the relationship with eGFR. The odds ratios for having a low eGFR, defined as the lowest quartile of eGFR (i.e., ≤78.4 mL/min/1. 73m2) was estimated according to SUA quartiles (men, Q1 ≤ 5.0, Q2 5.1–5.9, Q3 6.0–6.6, and Q4 ≥ 6.7; women, Q1 ≤ 3.8, Q2 3.9–4.3, Q3 4.4–4.9, and Q4 ≥ 5.0 mg/dL) after adjustment for age, body mass index, systolic blood pressure, HbA1c, high and low density lipoprotein cholesterol, and smoking and drinking habits. The adjusted mean of each quartile was also calculated. Results Multivariable-adjusted means of eGFR showed a graded decrease in higher SUA quartiles (men, Q1 90.5, Q2 88.0, Q3 83.5, and Q4 82.0; women, Q1 95.7, Q2 91.3, Q3 89.2, and Q4 86.7). In addition, the multivariable-adjusted odds ratios for having a lower eGFR (95% confidence interval) for each SUA quartile compared with Q1 was Q2 2.29 (0.98, 5.35), Q3 4.94 (2.04, 11.97), and Q4 8.01 (3.20, 20.04) for men, and was Q2 2.20 (1.12, 4.32), Q3 2.68 (1.39, 5.20), and Q4 4.96 (2.62, 9.41) for women. Conclusions There was a graded inverse relationship between mild elevations in SUA levels and eGFR assessed by cystatin C in an apparently healthy Japanese population without CKD. This association was similar in both men and women.

During the past 70 years, a relationship between low-density lipoprotein cholesterol (LDL-C) and coronary heart disease (CHD) incidence has been established in many countries. Evidence of causality has been provided by the prevention of CHD by reduction of LDL-C, most notably with statins. These findings have made it possible to develop risk assessment charts for CHD and to detect high-risk individuals for early intervention. However, a causal relation between lipids and stroke, an adverse effect on noncoronary mortality such as that due to intraparenchymal hemorrhage, and the roles of lipid parameters other than LDL-C remain controversial.