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This follow-up study was conducted over 30 years in a cadmium-polluted area of Japan. Urinary cadmium (U-Cd) concentration decreased by nearly half from 1986 to 2008 in men and women. However, it increased from 2008 to 2014 and maintained similar levels in 2016. Because renal atrophy may induce an increase in U-Cd, kidney volumes were determined using magnetic resonance imaging (MRI) scans in 2018. Based on the MRI results, we divided the participants into two groups, namely the normal group (n = 6, three men and three women) and the lesion group (n = 6, three men and three women). The level of urinary N-acetyl-β-d-glucosaminidase/creatinine (U-NAG/Cr) in the lesion group was significantly higher than in the normal group. The level of serum alkaline phosphatase (Al-P) was positively associated with U-Cd. Age and renal cortex volumes showed significantly negative associations. However, U-Cd and renal cortex and kidney volumes showed no significant associations. These results suggest that U-NAG and serum Al-P were sensitive biomarkers to reflect renal tubular dysfunction and bone damage caused by cadmium poisoning. Individuals chronically exposed to Cd should be observed carefully, due to the increased effect of aging on renal cortex volumes.

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40-59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (

The relationship between urinary β2 -microglobulin (β2 -MG) and the risk of all-cause mortality and cause-specific mortality in a cadmium (Cd)-polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35-year follow-up. The subjects had been participants in the 1981-1982 health impact survey that assessed Cd-induced renal dysfunction, as measured by the urinary β2 -MG concentration. Hazard ratios were calculated to assess the risk of all-cause and cause-specific mortality according to the urinary β2 -MG concentrations. Risk ratios (RRs) were assessed using the Fine and Gray regression model to account for competing risks of cause-specific mortality. The mortality rate was significantly higher in participants with urinary β2 -MG concentrations >1000 μg/g creatinine (Cr) for men and >300 μg/g Cr for women. In the proportional hazard model, higher urinary β2 -MG concentrations were associated with higher risks of circulatory disease, digestive system diseases, and kidney and urinary tract diseases in men and women, and with senility for women. However, when competing risk was accounted for, the RRs were significantly higher only for kidney and urinary tract diseases in men and women (RR for each increment of 1000 μg/g Cr [95% confidence interval]: 1.02 [1.00-1.04] for men, and 1.01 [1.00-1.02] for women). The long-term prognosis of participants with renal tubular dysfunction was poor, most likely due to kidney and renal tract diseases.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd (U-Cd) on cancer mortality in the general Japanese population. A 19-year cohort study was conducted in 1107 men and 1697 women who lived in three Cd non-polluted areas in Japan. Mortality risk ratio and 95% confidence interval (95%CI) for continuous U–Cd were estimated for all malignant neoplasms and specific cancers using a Fine and Gray competing risks regression model. The all-cause, including cancer and non-cancer mortality rates per 1000 person-years were 29.8 and 13.9 in men and women, respectively. By using Fine and Gray's method, continuous U–Cd adjusted for creatinine (+1 μg/g cre) was significantly related to mortalities for all malignant neoplasms (risk ratio = 1.06, 95%CI: 1.02–1.11) and pancreas (risk ratio = 1.13, 95%CI: 1.03–1.24) in women. In the present study, U–Cd was significantly associated with increased cancer mortality in the general Japanese population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan.

Background It is uncertain whether risk classification under the nationwide program on screening and lifestyle modification for metabolic syndrome captures well high‐risk individuals who could benefit from lifestyle interventions. We examined the validity of risk classification by linking the incidence of cardiovascular disease (CVD). Methods and Results Individual‐level data of 29 288 Japanese individuals aged 40 to 74 years without a history of CVD from 10 prospective cohort studies were used. Metabolic syndrome was defined as the presence of high abdominal obesity and/or overweight plus risk factors such as high blood pressure, high triglyceride or low high‐density lipoprotein cholesterol levels, and high blood glucose levels. The risk categories for lifestyle intervention were information supply only, motivation‐support intervention, and intensive support intervention. Sex‐ and age‐specific hazard ratios and population attributable fractions of CVD, which were also further adjusted to consider non–high density lipoprotein cholesterol levels, were estimated with reference to nonobese/overweight individuals, using Cox proportional hazard regression. Since the reference category included those with risk factors, we set a supernormal group (nonobese/overweight with no risk factor) as another reference. We documented 1023 incident CVD cases (565 men and 458 women). The adjusted CVD risk was 60% to 70% higher in men and women aged 40 to 64 years receiving an intensive support intervention, and 30% higher in women aged 65 to 74 years receiving a motivation‐support intervention, compared with nonobese/overweight individuals. The population attributable fractions in men and women aged 40 to 64 years receiving an intensive support intervention were 17.7% and 6.6%, respectively, while that in women aged 65 to 74 years receiving a motivation‐support intervention was 9.4%. Compared with the supernormal group, nonobese/overweight individuals with risk factors had similar hazard ratios and population attributable fractions as individuals with metabolic syndrome. Conclusions Similar CVD excess and attributable risks among individuals with metabolic syndrome components in the absence and presence of obesity/overweight imply the need for lifestyle modification in both high‐risk groups.

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.

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with

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.

Primary health care for mental health in workers should apply to actualities of workers’ stress coping and stress response. We conducted an assessment by cross-sectional study concerning stress coping, job stress, and stress response among IT employees in Japan. Subjects were 75 healthy new employees (males). We used the 54-item Maslach Burnout Inventory-General Survey (MBI-GS, domains: exhaustion, cynicism, professional efficacy), the Job Content Questionnaire (JCQ, domains: demand, control, social support), the General Coping Questionnaire (GCQ, domains: emotion expression, emotional support seeking, cognitive reinterpretation, problem solving).

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.

Aim: The positive relationship between dietary cholesterol and serum cholesterol has been questioned by a set of recent cohort studies. This study aimed to investigate how employment status and education years relate to the association between dietary cholesterol and serum low-density lipoprotein cholesterol (LDL-C) in a Japanese population. Methods: A population-based, random sample, cross-sectional study (INTERLIPID) was performed. Among 1,145 Japanese individuals aged 40–59 years, 106 were excluded because of special diets, use of lipid-lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls, and LDL-C was measured enzymatically with an autoanalyzer. A standard questionnaire inquired about employment status and education years. Results: In men, a 1 standard deviation (SD) higher dietary cholesterol was associated with 3.16 mg/dL lower serum LDL-C (P = 0.009; unadjusted model). After adjustment for covariates, higher serum LDL-C was estimated per 1 SD higher intake of dietary cholesterol in nonemployed men [self-employed, homemakers, farmers, fishermen, and retired employees; β = +9.08, 95% confidence interval (CI) = +0.90–+17.27] and less educated men (β = +4.46, 95% CI = −0.97–+9.90), whereas an inverse association was observed in employed men (β = −3.02, 95% CI= −5.49–−0.54) and more educated men (β = −3.66, 95% CI = −6.25–−1.07). Conclusions: In men who were nonemployed and less educated, a higher intake of dietary cholesterol was associated with elevated concentrations of serum LDL-C, whereas an inverse association was observed in men who were employed and more educated.

Dioxins have been suspected to be potential substances causing endocrine disruptions in humans. We are conducting the research in one of three dioxin exposure areas (hotspots) in Vietnam. We previously reported that the salivary dehydroepiandrosterone (DHEA) level decreased in 3-year-old Vietnamese children and that it was significantly inversely correlated with polychlorinated dibenzodioxin/dibenzofuran levels in their mother's breast milk. In this study, we investigated the influence of exposure to dioxin on steroid hormone biosynthesis in the same children when they reached 5 years of age, focusing on androgens. Thirty-five and 50 mother–child pairs from dioxin hotspot and non-sprayed areas, respectively, participated in this study. Maternal breast milk was donated at 4 to 16 weeks postpartum in 2008 to measure dioxin levels by gas chromatography/high-resolution mass spectrometry. Serum was collected from 5-year-old children in 2013. Seven steroid hormones were measured by liquid chromatography/mass spectrometry. Most dioxin congeners in breast milk were 2- to 10-fold higher in the hotspot than in the non-sprayed area. DHEA and testosterone (T) were significantly lower in the hotspot and showed negative correlations with most dioxin congeners. Similar results were observed for the activities of cytochrome P450-17, 20 lyase (CYP17 lyase), and 17β-hydroxysteroid dehydrogenase (HSD). Conversely, the elevated androstenedione (A-dione) level and 3β-HSD activity in children from the hotspot were positively correlated with dioxin levels. Moreover, a positive correlation was shown between T and 17β-HSD. It is possible that dioxin inhibits 17β-HSD activity, leading to a decrease in the T level. Multiple regression analysis indicated that dioxin had a strong association with the DHEA, A-dione, and T levels. In conclusion, the present study suggests that dioxin is associated with low levels of DHEA and T and inhibition of the activity of steroidogenic enzymes such as CYP17 lyase and 17β-HSD in 5-year-old children.

Objective This study investigated associations between three indices of obesity-the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR)-and the incidence of chronic kidney disease (CKD). Methods The employees of a company in Japan (1,725 men, 1,186 women; aged 35-55 years) had BMI, WC, and WHtR measured in health examinations. The incidence of CKD was determined at annual medical examinations over a six-year period. The hazard ratios for CKD were calculated using proportional hazard models, and the χ2 statistic was used to compare the strengths of the associations. Results The mean BMI (kg/m2), WC (cm), and WHtR were 23.6, 84.3, and 0.49 for men and 22.3, 79.7, and 0.50 for women, respectively. The incidence of CKD (/1,000 person-years) was 18.1 for men and 8.4 for women. In men, positive linear associations were observed between the BMI, WC, and WHtR and the risk of CKD, even after adjusting for the presence of metabolic abnormalities (p for trend

Aims/Introduction This cohort study assessed the risk for bodyweight gain and development of glucose intolerance based on the frequency of consumption of balanced meals including grain, fish or meat and vegetables. Materials and Methods The participants (8,573 men, 3,327 women) were employees of a company in Japan. A self‐administered questionnaire was used to evaluate the frequency of balanced meal consumption. Bodyweight changes and the incidence of glucose intolerance (glycated hemoglobin >6.0%) during the 3‐year follow‐up period were determined through annual health examinations. Results The mean bodyweight change over a period of 3 years was 0.78 kg for men and 0.84 kg for women. A lower frequency of balanced meals was associated with a higher bodyweight gain for men (P for trend = 0.004), but not for women. During the study, 464 men and 115 women developed glucose intolerance. Overall, the frequency of balanced meals was not associated with the risk of glucose intolerance in either sex. However, the interaction between the frequency of balanced meals and degree of obesity had a significant effect on the incidence of glucose intolerance in men (P = 0.005), with less frequent consumption of balanced meals being associated with a higher risk for glucose intolerance among men with a BMI ≥25.0 kg/m2 (P for trend = 0.007). Conclusions A higher frequency of balanced meals, including grain, fish or meat and vegetable dishes – important components of healthy Japanese food – was associated with a lower risk of glucose intolerance in obese men, but not in non‐obese men and women., We evaluated the risk for development of glucose intolerance based on the frequency of consumption of balanced meals including grain, fish and meat, and vegetable dishes. A lower frequency of balanced meals was associated with a higher risk of glucose intolerance in obese men.

The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U-Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U-Cd (μg/g cre) adjusted for urinary creatinine. Hazard ratio (HR) and 95% confidence interval (95% CI) for continuous U-Cd or the quartiles of U-Cd were calculated for noncancer mortality. By applying a Fine and Gray competing risk model, continuous U-Cd (+1 μg/g cre) showed significant HR for cardiocerebrovascular diseases (HR 1.05, 95% CI: 1.00-1.11), cerebrovascular diseases (HR 1.08, 95% CI: 1.01-1.16), and cerebral infarction (HR 1.11, 95% CI: 1.04-1.20) in men. However, notable significant HR for continuous and quartered U-Cd were not observed in women. In this study, U-Cd was associated with increased cardiocerebrovascular mortality in a general Japanese population, suggesting that environmental cadmium exposure is detrimental to the life prognosis in cadmium nonpolluted regions in Japan.

A lower-than-recommended potassium intake is a well-established risk factor for increased blood pressure. Although the Japanese diet is associated with higher sodium intake and lower potassium intake, few studies have examined the source foods quantitatively. Studies on dietary patterns in association with potassium intake will be useful to provide dietary advice to increase potassium intake. Twenty-four-hour (hr) dietary recall data and 24-hr urinary potassium excretion data from Japanese participants (574 men and 571 women) in the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were used to calculate food sources of potassium and compare food consumption patterns among quartiles of participants categorized according to 24-hr urinary potassium excretion per unit of body weight (UK/BW). The average potassium intake was 2791 mg/day per participant, and the major sources were vegetables and fruits (1262 mg/day), fish (333 mg/day), coffee and tea (206 mg/day), and milk and dairy products (200 mg/day). Participants in the higher UK/BW quartile consumed significantly more vegetables and fruits, fish, and milk and dairy products, and ate less rice and noodles. Conclusion: Advice to increase the intake of vegetables and fruits, fish, and milk may be useful to increase potassium intake in Japan.

BACKGROUND: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. METHODS AND RESULTS: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40–59 years in 1996–1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women. CONCLUSIONS: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

Background Many studies have reported the J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk; therefore, light-drinkers is generally recognized to be associated with the lower risk of CHD. However, the mechanisms of lower risk for CHD in light-drinkers are still unclear. Alcohol drinking status is likely to be associated with not only CHD risk factors but also dietary intake. Nevertheless, few studies report these relationships in detail. Purpose The purpose of this study is to evaluate the relationships of alcohol drinking status with CHD classical risk factors and the intake of macro- and micro- nutrients in Japanese. Methods Study participants were 1,090 Japanese men and women aged 40–59 years from The INTERLIPID study excepted for 55 individuals who had missing data (n=26) and were past-drinkers (n=29). Alcohol consumption was assessed with two 7-day alcohol records, and average ethanol intake (per week) was calculated. Participants were classified into following 4 groups: non-drinkers (0g/week), light-drinkers ( Results Serum HDL cholesterol levels increased and LDL cholesterol levels decreased with increasing alcohol consumption. Systolic and diastolic BP increased with increasing alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smoker, number of cigarettes, and the prevalence of hypertension; that is, light-drinkers was lowest among all groups. The prevalence of dyslipidemia was the highest in non-drinkers, and decreased with increasing alcohol consumption. In heavy-drinkers, total energy (kcal/day) was the highest, but energy intake without alcohol (kcal/day) was the lowest. For macronutrients, the intake of carbohydrate (%kcal) decreased, and the intakes of total and animal protein (%kcal) increased with increasing alcohol consumption. The intakes of total cholesterol (mg/1000kcal) and sodium (mg/1000kcal) increased, and total fiber (g/1000kcal) decreased with increasing alcohol consumption. These associations were similar in men and women. Conclusions Alcohol consumption was related with not only CHD classical risk factors but also the intake of macro- and micro-nutrients. Non-drinkers had a higher proportion of some CHD risk factors than light-drinkers. These results might influence on J-shaped relationship between alcohol consumption and CHD risk. Acknowledgement/Funding 1: Ministry of Education, Science, Sports, and Culture of Japan, 2: National Institutes of Health, Bethesda, MD, USA

Background This study investigated relationships among socioeconomic factors and participation in health examinations for Japanese National Health Insurance (NHI) using a representative Japanese population. Methods We used the linkage database of NIPPON DATA2010 and Comprehensive Survey of Living Conditions 2010. Participants with NHI aged 40-74 years were included in the analysis. Prevalence ratios (PRs) for participation in health examinations in the past year were set as an outcome. Participant characteristics, including sex, age, socioeconomic factors (educational attainment, employment, equivalent household expenditure [EHE], house ownership, and marital status), laboratory measures, and lifestyle were included in an age-stratified modified Poisson regression analysis to examine relationships. Results The number of study participants was 812, and 564 (69.5%) participated in health examinations in the past year. Among those aged 40-64 years, there was no significant PR for socioeconomic factors. Among those aged 65-74 years, high (≥13 years) educational attainment (adjusted PR, 1.22; 95% confidence interval [CI], 1.05-1.41) and house ownership (PR 1.40; 95% CI, 1.11-1.77) were positively associated with participation, while high (4th quartile) EHE (PR 0.84; 95% CI, 0.73-0.97) was negatively associated. Conclusion These results suggest that high educational attainment, house ownership, and low EHE were positive factors for participation in health examinations among those aged 65-74 years.

Although dietary soy intake is linked with health benefits, a relation with stroke has not been established. The present study examined the association between the intake of tofu, the richest source of dietary soy, with stroke mortality in a general population cohort of Japanese men and women.Data comprise 9244 Japanese enrolled in the National Nutrition Survey of Japan in 1980. Participants were free of cardiovascular disease and followed for 24 years. Dietary intake was estimated from 3-day weighed food records. Multivariable Cox regression models were used to estimate hazard ratios across levels of tofu intake.During follow-up, there were 417 deaths due to stroke (88 cerebral hemorrhage [CH], 245 cerebral infarction [CI], and 84 of other subtypes). Among all men, and in women aged 65 years or more, tofu intake was unrelated to each form of stroke. For young women (65 years of age), a significantly lower risk of CH in the top versus bottom quartile of tofu intake was observed (Multivariable-adjusted HR = 0.26, 95% CI: 0.08-0.85).In this large prospective study with long follow-up of Japanese men and women, consumption of tofu was unrelated to the risk of stroke except for CH in women65 years of age. Whether the association in younger women is real or due to chance alone warrants further study.

Since 2008, we have conducted epidemiological cohort studies on the relationship between dioxin exposure and disruption with children in the area sprayed with defoliants during the Vietnam War. In a long-term survey of children through the age of five, we observed androgen disruption due to decreased dehydroepiandrosterone (DHEA) and testosterone levels. In this study of 7-year-old, we separately elucidated androgen disruption for boys and girls, and discussed with respect to hormone disruption with sex differences on the steroid hormone biosynthesis process. This follow-up was conducted with 96 mother-child pairs in Vietnam (hotspot area: 45, non-sprayed area: 51). We took a questionnaire, the physical measurement and assayed 7 steroid hormones in their serum by LC-MS/MS. We examined the relationship between the hormone levels in the serum and dioxin levels in the maternal breast milk. The results showed that the serum DHEA level in the 7-year-old children in the hotspot recovered to levels in the non-sprayed area. The testosterone level of 66.5 pg/mL for boys in the non-sprayed area was 1.5 times the girls level of 44.6 pg/mL, a male-dominant effect. The testosterone level in boys and girls from the hotspot were significantly lower than in the non-sprayed area with no sex difference. The 17β-hydroxysteroid dehydrogenase (17β-HSD) activity was significantly higher in boys than in the girls from the non-sprayed area, but was significantly lower in the hotspot boys than in the non-sprayed area boys. Both the testosterone level and 17β-HSD activity in the boys were inversely correlated with the TEQ total PCDD/Fs in the maternal breast milk. These results indicated that dioxin delayed the expression of the testosterone level and 17β-HSD activity with growth in the 7-year-old boys. The serum DHEA in the 7-year-old children recovered to the levels of the children in the non-sprayed area.

SummaryObjective This study investigated the relationship between frequency of skipping breakfast and annual changes in body mass index (BMI) and waist circumference (WC). Methods The participants were 4,430 factory employees. BMI and WC were measured repeatedly at annual medical examinations over a 5-year period. The association between frequency of skipping breakfast at the baseline examination and annual changes in anthropometric indices was evaluated using the generalized estimating equation method. Results The mean (standard deviation) BMI was 23.3 (3.0) kg m−2 for men and 21.9 (3.6) kg m−2 for women; and the mean WC was 82.6 (8.7) cm for men and 77.8 (9.8) cm for women. During the follow-up period, mean BMI increased by 0.2 kg m−2 for men and women, and mean WC increased by 1.1 cm for men and 1.0 cm for women. The annual change in the BMI of men who skipped breakfast four to six times per week was 0.061 kg m−2 higher, and that of those who skipped breakfast seven times per week was 0.046 kg m−2 higher, compared with those who did not skip breakfast. Annual changes in the WC of male participants who skipped breakfast seven times per week was 0.248 cm higher than that of those who did not skip breakfast. Skipping breakfast was not associated with changes in BMI or WC in women. Conclusions Skipping breakfast was closely associated with annual changes in BMI and WC among men, and eating breakfast more than four times per week may prevent the excessive body weight gain associated with skipping breakfast.

Background Diabetes mellitus is a strong risk factor for cardiovascular disease. However, the age-specific association of diabetes with cardiovascular risk, especially in the elderly, remains unclear in non-Western populations. Methods A pooled analysis was conducted using 8 cohort studies (mean follow-up period, 10.3 years) in Japan, combining the data from 38,854 individual participants without history of cardiovascular disease. In all, 1867 of the participants had diabetes, defined based on the 1998 World Health Organization criteria. The association between diabetes and the risk of death from cardiovascular disease, coronary heart disease (CHD), and stroke was estimated using a stratified Cox model, accounting for variability of baseline hazard functions among cohorts. Results During the follow-up, 1376 subjects died of cardiovascular disease (including 268 of coronary heart disease and 621 of stroke). Diabetes was associated with an increased risk of cardiovascular death after multivariable adjustment (hazard ratio [HR] 1.62; 95% confidence interval [CI], 1.35–1.94). Similarly, diabetes was a risk factor for CHD (HR 2.13; 95% CI, 1.47–3.09) and stroke (HR 1.40; 95% CI, 1.05–1.85). In the age-stratified analysis of the risk of cardiovascular death, the relative effects of diabetes were consistent across age groups (p for heterogeneity = 0.18), whereas the excess absolute risks of diabetes were greater in participants in their 70s and 80s than in younger subjects. Conclusions The management of diabetes is important to reduce the risk of death from cardiovascular disease, not only in midlife but also in late life, in the Japanese population., Highlights • We conducted meta-analysis of individual data from 8 Japanese cohorts (n = 38,854). • Diabetes raised cardiovascular mortality in Japan. • Impact of diabetes on cardiovascular death was similar across 10-year age groups.

The absorption of cadmium (Cd) may lead to Cd-related diseases such as renal tubular dysfunction and bone disease, and it is known to take around 10-30 years to reduce Cd concentrations to half their original levels. Urinary β2 -microglobulin (β2 -MG), N-acetyl-β-D-glucosaminidase (NAG), protein, glucose and albumin were used as indicators of renal dysfunction caused by Cd exposure. Our previous study found that urinary Cd concentrations had increased recently and that age was more strongly associated with urinary β2 -MG concentration than recent Cd body burden. Therefore, the purpose of the present study was to investigate the effect of aging on Cd concentrations and renal dysfunction. The Cd, β2 -MG, NAG, protein, glucose and albumin concentrations in the urine of 40 Japanese subjects (20 females and 20 males) environmentally exposed to Cd were collected. They lived in the Kakehashi River basin and were divided into three age categories: 50-69, 70-79 and 80-99 years. Significant differences in urinary Cd and β2 -MG concentrations were found among age groups, with urinary Cd levels tending to increase with age in both sexes. No significant correlations were found between urinary Cd and any indicators of renal dysfunction. The correlation between age, Cd and indicators of renal dysfunction was observed more clearly in females than in males. Age is more strongly correlated with indicators of renal dysfunction than Cd body burden. Copyright © 2017 John Wiley & Sons, Ltd.

The aim of this study is to estimate the reference level of lifetime cadmium intake (LCd) as the benchmark doses (BMDs) and their 95% lower confidence limits (BMDLs) for various renal effects by applying a hybrid approach. The participants comprised 3,013 (1,362 men and 1,651 women) and 278 (129 men and 149 women) inhabitants of the Cd-polluted and nonpolluted areas, respectively, in the environmentally exposed Kakehashi River basin. Glucose, protein, aminonitrogen, metallothionein, and β2 -microglobulin in urine were measured as indicators of renal dysfunction. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at zero exposure set at 5%. The obtained BMDLs of LCd were 3.7 g (glucose), 3.2 g (protein), 3.7 g (aminonitrogen), 1.7 g (metallothionein), and 1.8 g (β2 -microglobulin) in men and 2.9 g (glucose), 2.5 g (protein), 2.0 g (aminonitrogen), 1.6 g (metallothionein), and 1.3 g (β2 -microglobulin) in women. The lowest BMDL was 1.7 g (metallothionein) and 1.3 g (β2 -microglobulin) in men and women, respectively. The lowest BMDL of LCd (1.3 g) was somewhat lower than the representative threshold LCd (2.0 g) calculated in the previous studies. The obtained BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure.

Objectives: The present cohort study investigated the relationship between serum ferritin levels and indices of insulin resistance and β-cell dysfunction in a normoglycemic population without iron overload disorders. Methods: The study participants included 575 normoglycemic Japanese men aged 35–57 years with serum ferritin levels of 400 μg/L or less. Insulin resistance and β-cell dysfunction were estimated at baseline and after 3 years by the homeostasis model assessments of insulin resistance and β-cell function (HOMA-IR and HOMA-β, respectively). To compare the subsequent changes in HOMA-IR and HOMA-β over a 3-year follow-up period among 3 groups based on tertiles of baseline serum ferritin levels (4.9–87.1, 87.2–140.5, and 140.6–396.8 μg/L), the geometric mean HOMA-IR and HOMA-β values at year 3 were calculated for each group using analysis of covariance, incorporating the respective log-transformed parameters at baseline in addition to age, body mass index and major confounding factors. Results: The multivariate-adjusted geometric mean HOMA-IR at year 3 was significantly higher in those in the highest and middle serum ferritin tertiles (1.24 and 1.22, respectively), compared with the lowest tertile (1.07) (p=0.009). When the total study participants were stratified by median body mass index (22.72 kg/m2), similar positive relationships were observed between serum ferritin levels and HOMA-IR for both obese and non-obese participants. However, the adjusted geometric mean HOMA-β at year 3 was similar among the 3 serum ferritin groups. Conclusions: Elevated serum ferritin levels predicted a subsequent increase in HOMA-IR in normoglycemic Japanese men without iron overload disorders.

Objectives The increasing number of working elderly people has enhanced the importance of workplace health promotion activities. We investigated the association between the health status of workers approximately 60 years of age and the risk of all‐cause mortality after compulsory retirement in Japan. Methods The 2026 participants (1299 males and 727 females) had retired from a metal‐products factory at ≥60 years of age. Baseline health examinations were conducted at 60 years of age and included questions about medical history and lifestyle factors; the participants also underwent a physical examination. The participants were followed up annually by mail for an average of 7.4 years. The association between health status at age 60 years and the risk of all‐cause mortality was assessed by Cox proportional hazards regression analysis. Results During the study, 71 deaths were reported. The age‐ and sex‐adjusted hazard ratio (HR [95% confidence interval]) for all‐cause mortality was higher for males (HR, 3.41 [1.73‐6.69]) compared with females, participants with a low body mass index (

The increased cancer incidence and mortality associated with cadmium (Cd) exposure have been investigated worldwide, but the findings are often inconsistent. The increased mortality from cardiovascular and other non-cancer diseases has also been reported in populations exposed to Cd. In Japanese Cd-polluted areas, including one where itai-itai disease is endemic, levels of urinary Cd and renal tubular dysfunction induced by Cd exposure are associated with an increased mortality in both sexes (women > men), particularly from cardiovascular and renal diseases. However, deaths from respiratory and digestive diseases have also been recorded in patients with itai-itai disease. Significant association between Cd in rice and mortality was found only in the most polluted part of the Jinzu River basin, Toyama in Japan. These findings indicate that high-level Cd exposure, whether environmental or occupational, may adversely affect life prognosis, but more studies are required to characterize the effects of low-level Cd exposure indicated by urinary or blood Cd in general populations with different dietary and lifestyle habits.

Very few studies have investigated the dose–response relationship between external cadmium (Cd) exposure and mortality. We aim to investigate the relationship between lifetime Cd intake (LCd) and mortality in the Cd-polluted Kakehashi River basin in Japan. Mortality risk ratios for a unit of increase of LCd and urinary Cd were analyzed using Cox’s proportional model. LCd was estimated based on residency and Cd in rice produced in their living areas. In men, mortality for all causes was significantly increased for a 10-μg/g Cr increase in urinary Cd, but not for a 1-g increase in LCd. In women, mortality risks for all causes and renal diseases, particularly renal failure, were significantly increased for a 10-μg/g Cr increase in urinary Cd. Similarly, mortality risks for renal diseases and renal failure were significantly increased for a 1-g increase of LCd in women. Comparing the contribution of two exposure markers to increased mortality in women, LCd was more effective for increasing mortality risks for renal diseases and renal failure, while urinary Cd contributed more to increased mortality risk for all causes. LCd may show a better dose–response relationship with mortality risk for renal diseases in women.

Aims: The present study aimed to investigate relationships among abdominal obesity, metabolic abnormalities, and the prevalence of chronic kidney disease (CKD) in relatively lean Japanese men and women. Participants and methods: The participants included 8133 men and 15 934 women between 40 and 75 years of age recruited from the government health check-up center in Kanazawa City, Japan. The prevalence of abdominal obesity, high blood pressure, dyslipidemia, and high fasting plasma glucose levels were assessed according to the Japanese criteria for metabolic syndrome. The estimated glomerular filtration rate (eGFR) was calculated using the modified Modification of Diet in Renal Disease equation for the Japanese population, and participants with an eGFR

The biological half-life of cadmium (Cd) is as long as 10-30 years. Exposure to this element induces renal tubular dysfunction, which is considered irreversible. β2 -microglobulin (β2 -MG) is a low-molecular-weight protein, and urinary β2 -MG is one of the most useful and critical indicators for the early detection of renal tubular dysfunction. However, very little research has been published concerning the long-term observation of Cd-induced adverse health effects. As such, this follow-up study was conducted for 28 years to clarify the relationship between the concentration of Cd and β2 -MG in the urine of 28 inhabitants (14 male and 14 female) living in the Kakehashi River basin, Ishikawa prefecture (Japan), previously one of the most highly Cd-polluted regions in this country. All subjects were over 60 years old in 2014 and participated in all six health examinations conducted over 28 years (1986-2014). Urine was collected at the appropriate time and kept frozen to analyze urinary Cd and β2 -MG concentrations. The urinary Cd concentration was found to decrease by nearly half between 1986 and 2008 in both male and female subjects, whereas it increased significantly from 2008 to 2014 in males. In contrast, urinary β2 -MG concentrations tended to increase over the 28-year study period in both sexes. Urinary Cd and β2 -MG concentrations in females were significantly higher than those in males in this Cd-polluted region. Age is more strongly associated with urinary β2 -MG concentration than recent Cd body burden. Copyright © 2016 John Wiley & Sons, Ltd.

Most studies on the relationship between Agent Orange and prostate cancer have focused on US veterans of the Vietnam War. There have been few studies focusing on the relationship between levels of prostate-specific antigen (PSA) and dioxins or steroid hormones in Vietnamese men. In 2009–2011, we collected blood samples from 97 men who had resided in a “dioxin hotspot” and 85 men from a non-sprayed region in Vietnam. Then levels of PSA, dioxins, and steroid hormones were analyzed. Levels of most dioxins, furans, and non-ortho polychlorinated biphenyls were higher in the hotspot than those in the non-sprayed region. Levels of testosterone, dehydroepiandrosterone, and estradiol differed significantly between the hotspot and the non-sprayed region, but there were no correlations between levels of PSA and steroid hormones and dioxins in either of the two regions. Our findings suggest that PSA levels in Vietnamese men are not associated with levels of dioxin or steroid hormones in these two regions. © 2016 Springer-Verlag Berlin Heidelberg, Embargo Period 12 months

Half-life of urinary cadmium level (U-Cd) was estimated in inhabitants whose initial U-Cd was ≥5 μg/L (131 men and 177 women) or ≥5 μg/gcr (195 men and 246 women), using a linear mixed model adjusted for the baseline age. To clarify the effect of initial U-Cd, the target participants were divided into higher or lower initial U-Cd group. In the higher groups, the half-lives were 15.4 and 13.1 years for unadjusted U-Cd and 19.0 and 23.0 years for creatinine-adjusted U-Cd, in men and women, respectively. In the lower groups, the half-lives were 38.0 and 26.0 years for unadjusted U-Cd in men and women. For creatinine-adjusted U-Cd, it was 42.9 years in men. For attenuation of U-Cd, there were an early fast component shown in the higher group and late slow component shown in the lower group. The attenuation of U-Cd is slower in the longer time compared to that previously reported.

PURPOSE: It is often reported that Na intake levels are higher in Japan than in western countries. Detailed analysis of food intake and its association with Na intake are necessary for supporting further decreases in Na consumption in Japan. We investigated the association between Na and food intake by food group using data from the Japanese participants of the INTERMAP Study. METHOD: Results from the Japanese participants of the INTERMAP Study who did not use antihypertensive medication and/or consume a reduced Na diet were used (531 men and 518 women, aged 40–59 years), obtained from four 24-h dietary recalls and two 24-h urine collections from each participant. We developed a classification system with 46 food group classifications; food consumption and Na intake from these groups were compared across quartiles of participants determined by 24-h urinary Na excretion per unit of body weight (UNa/BW). RESULTS: Average daily Na intake from Japanese high-Na foods was 2552 mg/day. Participants with a higher UNa/BW consumed a significantly greater amount of high-Na Japanese foods, such as salted fish (P = 0.001) and miso soup (P < 0.001). They also had greater amount of rice (P = 0.001). Participants with lower UNa/BW consumed a significantly greater amount of western foods, such as bread (P < 0.001) and milk and dairy products (P < 0.001). CONCLUSIONS: Detailed analyses of various Japanese and western food intakes in addition to Na intake were performed. These results can be used to help draw up effective programs for the reduction in Na intake and prevention of prehypertension/hypertension in the Japanese population.

A Japanese-style diet consists of meals that include grain (shushoku), fish and meat (shusai), and vegetable dishes (fukusai). Little is known about the association of such meals (designated well-balanced meals hereafter) with nutrient intake. We therefore examined the frequency of well-balanced meals required to prevent nutrient deficiency. Participants were Japanese people, ages 40 to 59 y, from Toyama, recruited for INTERMAP, in an international population-based study. Each person provided 4 in-depth 24-h dietary recalls (149 men, 150 women). The prevalence of risk ratios of not meeting the Dietary Reference Intakes for Japanese (2015) was calculated. Well-balanced diets were assessed by the Japanese Food Guide Spinning Top. We counted the frequencies of meals in which participants consumed 1.0 or more servings of all 3 dishes categories. We divided the frequency of consumption of well-balanced meals into the following 4 groups

The present cohort study assessed the risk among Japanese men for developing type 2 diabetes, based on the percentage of energy intake from carbohydrates and degree of obesity. Participants and Methods: The participants were 2,006 male factory employees, and the macronutrient intake of each patient was measured using a self-administered diet history questionnaire. The incidence of diabetes was determined in annual blood examinations over a 10-year period. Results: During the study, 232 participants developed diabetes. The crude incidence rates (/1,000 person-years) for different levels of carbohydrate intake as a percentage of calories consumed (65.0% of energy intake) were 16.5, 14.4, 12.7 and 17.6. Overall, carbohydrate intake was not associated with the risk of diabetes. However, there was significant interaction between carbohydrate intake and degree of obesity on the incidence of diabetes (P for interaction = 0.024). Higher carbohydrate intake was associated with elevated risk for diabetes among participants with a body mass index ≥25.0 kg/m2 (P for trend = 0.034). For obese participants, the multivariate-adjusted hazard ratio for those with carbohydrate intakes >65% energy was 2.01 (95% confidence interval 1.08-3.71), which was significantly higher than that of participants with carbohydrate intakes 50.0-57.4% energy. Conclusions: Higher carbohydrate intake was associated with higher risk of diabetes in obese participants, but not in non-obese participants. Obese participants with carbohydrate intakes >65% energy should reduce their intakes to levels within the desirable carbohydrate energy proportion for Japanese (50-65% energy) to prevent development of type 2 diabetes. © 2016 Asian Association for the Study of Diabetes and John Wiley & Sons Australia, Ltd.

Recent studies have found elevated dioxin levels inside some former US military air bases in Vietnam, known as hotspots. The aim of the present study was to evaluate the association of dioxin exposure and steroid hormone in preschool children in Vietnam. In 2010, 2011, 52 primiparae mother–infant pairs in the hotspot and 52 pairs in a non-exposure region were enrolled. For the final analysis, 26 vs 26 pairs were selected, who participated at all three surveys. Univariable and multivariable linear regressions were used to evaluate associations between hormone and dioxin congeners. Geometric mean total TEQ of PCDD/DFs in the hotspot were significantly higher than in the non-exposure region, 8.7 and 3.4 pg TEQ/g lipid, respectively. In the hotspot, salivary dehydroepiandrosterone (DHEA) was significantly higher in 1-year-old children (Boys = 123 pg/mL, Girls = 120 pg/mL) than in the non-exposure region (Boys = 28 pg/mL, Girls = 27 pg/mL). In contrast, DHEA was significantly lower in 5-year-old children (Boys = 70 pg/mL, Girls = 106 pg/mL) in the hotspot than in the non-exposure region (Boys = 496 pg/mL, Girls = 654 pg/mL). Salivary testosterone was significantly lower in the hotspot (Boys = 1.9 pg/mL, Girls = 1.9 pg/m; Boys = 1.0 pg/mL, Girls = 1.1 pg/mL, respectively) than in the non-exposure region (Boys = 3.7 pg/mL, Girls = 3.8 pg/m; Boys = 5.7 pg/mL, Girls = 7.0 pg/mL, respectively) at 3 years and 5 years of age. Higher levels of highly chlorinated dioxins in breast milk were associated with higher DHEA in 1-year-old and lower DHEA and testosterone levels in 5-year-old children. Our findings indicated that dioxins were associated with changes of DHEA and testosterone levels in preschool Vietnamese children.

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40–59 years from four countries (Japan, the People’s Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

Background: This study examined the relationships among household income, other SES indicators, and macronutrient intake in a cross-sectional study of a representative Japanese population. Methods: In 2010, we established a cohort of participants in the National Health and Nutrition Survey (NHNS) from 300 randomly selected areas throughout Japan. A total of 2,637 participants (1,145 men and 1,492 women) were included in the study. Data from NHNS2010 and the Comprehensive Survey of Living Conditions 2010 (CSCL2010) were merged, and relationships among macronutrient intake and SES were evaluated. Additionally, socioeconomic factors associated with a risk of a higher carbohydrate/lower fat intake beyond dietary recommendations were evaluated. Results: Household income was positively associated with fat intake (P = 0.001 for men and

Background: Although socioeconomic status (SES) may affect food and nutrient intakes, few studies have reported on sodium (Na) and potassium (K) intakes among individuals with various SESs in Japan. We investigated associations of SES with Na and K intake levels using urinary specimens in a representative Japanese population. Methods: This was a cross-sectional study of 2,560 men and women (the NIPPON DATA2010 cohort) who participated in the National Health and Nutrition Survey Japan in 2010. Casual urine was used to calculate estimated excretion in 24-hour urinary Na (E24hr-Na) and K (E24hr-K). The urinary sodium-to-potassium (Na/K) ratio was calculated from casual urinary electrolyte values. An analysis of covariance was performed to investigate associations of aspects of SES, including equivalent household expenditure (EHE), educational attainment, and job category, with E24hr-Na, E24hr-K, and the Na/K ratio for men and women separately. A stratified analysis was performed on educational attainment and the job category for younger (

Background Exposure to cadmium (Cd) via food is supposed to affect life prognosis of inhabitants of Cd-polluted area in Japan. However, there have been few reports demonstrating a significant relationship between the amount of Cd intake and mortality. We aimed to investigate the relationship between mortality and individual lifetime Cd intake (LCd) in inhabitants of the polluted Jinzu River basin, Toyama, Japan. Methods We conducted a 26-year follow-up survey in 2407 inhabitants (1208 men and 1199 women) who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The calculation of LCd in each inhabitant was based on the formula of Nogawa (Nogawa et al., 1989): (mean Cd concentration in rice of the present hamlet × 333.5 g/day + 34 μg/day) × 365 days/year × number of years of residence in the present hamlet + 50 μg/day × 365 days/year × number of years living in Cd non-polluted regions. In this formula, 333.5 g/day is the 1970 average daily intake of rice in this area, 34 µg/day is the Cd intake from foods other than rice in this area, and 50 μg/day is the average intake of Cd in non-polluted areas in Japan. Mortality risk ratios of LCd for all and specific causes were estimated after adjustments for age at baseline, smoking status, and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. Results The mortality risk ratios of LCd (+ 1 g) for all causes in women were significantly dose-dependently increased (risk ratio: 1.08). Relative risk of LCd for kidney and urinal tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly higher in women. Conclusions The present study documents that individual LCd dose-dependently decreased life prognosis over long-term observation in women. LCd was significantly related to the increased mortality for renal disease and toxic effect of Cd in women. The result provides clear evidence that life prognosis was adversely affected by Cd-exposure, especially in women.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all-cause mortality in the Japanese general population. A 19-year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non-polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U-Cd (µg g−1 cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U-Cd or the quartiles of U-Cd were estimated for all-cause mortality using a proportional hazards regression.The all-cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U-Cd (+1 µg g−1 cre) was significantly related to the all-cause mortality in men (HR 1.05, 95% CI: 1.02–1.09) and women (HR 1.04, 95% CI: 1.01–1.07). Furthermore in men, the third (1.96–3.22 µg g−1 cre) and fourth quartile (≥3.23 µg g−1 cre) of U-Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03–1.77, fourth: HR 1.64, 95% CI: 1.26–2.14) for all-cause mortality compared with the first quartile (

Objective To determine whether combinations of two odorants of the Open Essence smell identification test can be used to screen for olfactory impairment in Japanese people. Methods A total of 243 Japanese subjects (142 males, 101 females; mean age, 37.5 years; age range, 20–62 years) were enrolled in the study. The main outcome measures were the results of olfactory testing by using the full 12 odorants (condensed milk, cooking gas, curry, cypress wood (Japanese cypress, hinoki ), India ink, Japanese orange ( mikan ), menthol, perfume, roasted garlic, rose, sweaty-smelling clothes, and wood) of the Open Essence test as well as combinations of two odorants of the Open Essence test, and the results of self-reported questionnaires addressing awareness of a smell disorder, history of sinunasal disease, self-reported nasal obstruction, and history of smoking. Results In screening with combinations of two odorants, the highest positive likelihood ratio (19.1) was obtained with the cypress wood and India ink odorants. All subjects correctly identified the curry odorant. Combinations of other odorants also had high positive likelihood ratios (India ink and sweaty-smelling clothes, 17.6; perfume and sweaty-smelling clothes, 14.7; cypress wood and roasted garlic, 14.1; cypress wood and rose, 13.2; cypress wood and perfume, 11.0; cypress wood and wood, 10.7). Conclusion The combination of cypress wood and India ink odorants may be useful for detecting individuals with olfactory impairment among subjects who can correctly identify the curry odorant.

Aims To examine the relation of insulin resistant status determined by homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of incident hyperuricemia. Methods The study participants included 2071 Japanese men without hyperuricemia and diabetes, aged 35–54 years. The participants had undergone annual heath examinations for 6 years to compare incident hyperuricemia (serum uric acid >416.4 μmol/L (7.0 mg/dL) and/or taking medication for hyperuricemia) in four groups based on quartiles of baseline HOMA-IR. Results During follow-up there were 331 incident cases of hyperuricemia. The hazard ratios for hyperuricemia, compared with HOMA-IR ≤0.66, were 1.42 (95% confidence interval 1.02–1.98) for HOMA-IR 0.67–0.98, 1.20 (0.86–1.68) for HOMA-IR 0.99–1.49 and 1.44 (1.04–1.98) for HOMA-IR ≥1.50 after adjustment for baseline serum uric acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol intake, and smoking and exercise habits. The hazard ratio associated with an increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard deviation of HOMA-IR) was 1.14 (1.03–1.28) ( p for trend = 0.02). Conclusions Increased HOMA-IR independently predicted the subsequent development of hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may contribute to the development of hyperuricemia.

The aim of this study was to investigate the relationship between mortality and rice cadmium (Cd) concentration in inhabitants of a polluted area in Japan. The target subjects were inhabitants of the Jinzu River basin who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The mean rice Cd concentration in each hamlet was used as an index of the Cd exposure. We conducted a 26 year follow-up survey in 3281 inhabitants (1544 men and 1737 women) whose data regarding the rice Cd concentration were available. Mortality risk ratios for all and specific causes were estimated after adjustments for age at baseline, smoking status and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. The mortality risk ratios of rice Cd concentration (+0.1 ppm) for all causes in women were significantly increased (risk ratio: 1.04). Furthermore, the relative risks of rice Cd concentration for kidney and urinary tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly increased in both sexes. These findings indicated that increased rice Cd concentration decreased the prognosis for life over a long-term observation in women. This result provides important information for determining the worldwide standard for allowable rice Cd concentration.

Idiopathic olfactory disorder is resistant to treatment, and the recovery time is long. This study investigated the prognostic value of the migration of nasally administered thallium-201 to the olfactory bulb (thallium migration to the OB), a measure of olfactory nerve damage, in patients with idiopathic olfactory disorders. Twenty-four patients with idiopathic olfactory disorders were enrolled in the study (7 women and 17 men; aged 23–73 years). We retrospectively analyzed potential prognostic markers in subjects who underwent thallium-based olfactory imaging with the nasal administration of thallium-201 before conventional treatment with the Japanese herbal medicine tokishakuyakusan and compared those data with the prognosis. Log-rank tests were performed to assess the relationship between thallium migration to the OB (

Background: Immigration studies reported that dyslipidemia is more prevalent in people living in a western lifestyle. However, it is not clear what kind of lifestyle and dietary factors contribute to this difference. Aim: To investigate whether lifestyle including dietary factors could explain the difference in serum lipids between Japanese in Japan and Japanese-Americans in Hawaii living a western lifestyle. Methods: Analyses were conducted in the INTERLIPID study, where four standardized in-depth 24-h dietary recalls were performed. Non-fasting blood was drawn from the participants who included 1,087 Japanese and 176 Japanese-American. Participants’ characteristics were described as means and SD , t test was used for the comparison of means between Hawaii and Japan. Multiple linear regression models were used to examine relationships between dietary and lifestyle factors and the difference in serum lipids levels (low-density lipoprotein cholesterol [LDL-C] and log transformed triglycerides [log-TG]) between Hawaii and Japan, adjusting for age, sex and site as the basic model. Other confounders were then added separately to the basic model. Percentage reduction of regression coefficient for the difference between Hawaii and Japan was calculated. Results: In men, LDL-C levels were significantly higher in Japanese-Americans (138.3 mg/dl) compared to Japanese in Japan (120.3mg/dl, P Conclusion: BMI explained about half of the higher LDL-C and TG levels in Japanese-Americans in Hawaii compared to Japanese in Japan. BMI together with other macro-nutrients contributed to about 70% of the difference. Further investigation is required to explore the remaining difference.

We investigated the relation between overall sleep status based on the modified Pittsburgh Sleep Quality Index (PSQI) global score and subsequent changes in serum high-sensitivity C-reactive protein (hsCRP) in a population of Japanese factory workers, who were predominantly female. A total of 991 Japanese with inflammation classified as low cardiovascular risk (baseline hsCRP 1.0 mg L(-1) ) were grouped according to the presence or absence of unfavourable sleep, defined as a modified PSQI global score 5.5 points. The subsequent changes in hsCRP after 3 years were then compared in the two groups. Analysis of covariance incorporating log-transformed baseline hsCRP, age, sex, lifestyle and physical and biochemical profiles was used to compare the geometric means of hsCRP at year 3 in each sleep status group. A logistic regression model incorporating the same variables was used to calculate the odds ratios for development of inflammation with a medium-to-high cardiovascular risk (hsCRP at year 3 ≥ 1.0 mg L(-1) ) comparing the presence or absence of unfavourable sleep habits. The multivariate-adjusted geometric mean of hsCRP at year 3 was significantly higher in subjects with unfavourable sleep habits compared with those with a normal pattern (0.275 versus 0.242 mg L(-1) ). The multivariate-adjusted odds ratio for developing increased and potentially pathogenic levels of inflammation due to unfavourable sleep was 2.08 (95% confidence interval = 1.29-3.35). There was a significant linear trend for the development of increased inflammation across the modified PSQI global scores (P = 0.04). Unfavourable sleep is associated with activation of low-grade systemic inflammation.

The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and mortality. A 19-year cohort study was conducted in 900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary β2-microglobulin (β2-MG) and N-acetyl-β-glucosaminidase (NAG) for mortality were calculated using a proportional hazard regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Simultaneously, the dose-effect relationship between renal tubular markers and urinary cadmium at baseline was evaluated using multiple regression analyses. In men, HR was significant for β2-MG (HR corresponding to an increase of 100 μg/g cre: 1.02) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.05). In women, a significant HR was observed for β2-MG (HR corresponding to an increase of 100 μg/g cre: 1.01) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for urinary cadmium and all renal tubular markers in men and women. The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium non-polluted areas in Japan.

Aims: The aim of this study was to investigate age-related differences in the relationship between work-related factors and heavy drinking. METHODS: This study in 3398 male workers at a factory in Japan examined data on heavy drinking, defined as an alcohol consumption >40 g/day, and work-related factors including occupation, shift work, and job stress evaluated using the Japanese version of the Karasek's Job Content Questionnaire (JCQ). In the present cross-sectional study, alcohol consumption was assessed using a self-administered diet history questionnaire (DHQ). RESULTS: The prevalence of heavy drinkers in the study population was 15.5% and rose with increasing age. An increase in the odds ratio (OR) for heavy drinking was observed consistently in blue-collar workers compared with white-collar workers in all age groups. In subjects aged 20-29 years, shift work had also increased the OR for heavy drinking. In subjects aged 40-49 years, the two groups with a lower decision latitude had an increased OR compared with the highest group. The adjusted OR for individuals who received the lowest level of social support in the workplace was increased significantly compared with the highest group (4.22 [95%CI, 1.07-16.62]). On the other hand, social support showed a positive association with heavy drinking in subjects aged 40-49 and 50-59 yr. Job demand was not related to heavy drinking in any of the age groups. CONCLUSION: Our findings suggest that occupation and work schedule are related to alcohol use more apparently in a younger age group and that psychosocial factors are related to enhancement or prevention of alcohol use. Language: en