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Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

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.

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.

The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary β2-microglobulin (β2MG) and N-acetyl-β-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02-1.19, pancreas: HR, 1.10, 95%CI, 1.02-1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67-0.96) and for β2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93-1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.

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

Purpose We recently reported that children and adolescents with a history of Kawasaki disease (KD) had slight but significant elastic arterial stiffness even when no coronary artery lesions (CALs) were present. Moreover, we hypothesized that KD-related arteriopathy may also cause peripheral artery dysfunction. The objective of this study was to assess the involvement of radial artery pulse waves, especially reflection waves from the peripheral arteries using the radial artery augmentation index (rAI) in patients without CALs after KD. Materials and methods We first collected the rAI data from 312 subjects (149 consecutive patients of KD and 163 control subjects). Next, 225 cases between 6 and 15 years old were selected. Finally, 41 pairs were included for analysis. The rAI values of these two groups were compared and analyzed. Acute-phase data were also collected to reveal the possible correlation with rAI in the convalescent period. Results Multivariable analysis revealed the history of KD was positively correlated with rAI@75 value in children from 6 to 15 years old. After pairing the height and gender, the KD group also had significantly higher rAI and rAI@75 than the control group (rAI 60.63±13.77 vs 54.56±13.17, p=0.028; rAI@75 63.61±15.21 vs 55.68±14.86, p=0.003). With regard to acute-phase condition, nonresponse to initial treatment was also linked to elevated rAI during the convalescent period. Conclusions During the convalescent period, the rAI increased in KD patients without acute CALs. Furthermore, nonresponse to initial treatment in acute phase conferred higher rAI to KD subjects than respondent cases. Elevated rAI means the reflection wave from the peripheral vascular is stronger or earlier. This small but significant change may indicate the existence of peripheral artery stiffness during the convalescent period.

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.

The relationship between urinary β

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.

The aim of this study was to estimate the benchmark dose (BMD) as the threshold limit level of the cadmium (Cd) concentration in rice for itai-itai disease and/or suspected disease; it was based on the data that previously evaluated the association for such diseases with the Cd concentration in rice by using a logistic regression model. From 1971 to 1976, a total of 2446 rice samples were analyzed across the 88 hamlets in the Jinzu river basin. The mean Cd concentration in rice in each hamlet was used as the index of external Cd exposure of the entire population of the hamlet. We employed the incidence of itai-itai disease and/or suspected disease obtained from the available 55 hamlets. As the threshold, the lower limit of the BMD (BMDL) of the Cd concentration in rice for itai-itai disease and/or suspected disease was estimated using a logistic model, setting the benchmark response at 1% or 2%. The estimated BMDLs of the Cd concentration in rice for itai-itai disease and/or suspected disease were 0.62–0.76 and 0.27–0.56 mg kg−1 in men and women, respectively. The lowest BMDL was 0.27 mg kg−1 in women. In the present study, the threshold limit level of the Cd concentration in rice for itai-itai disease, which is the most severe form of chronic Cd poisoning, was estimated for the first time. This result provides important information about the worldwide standard for the Cd concentration in rice. Copyright © 2017 John Wiley & Sons, Ltd.

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 (

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.

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.

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 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.

We investigated the biological half-life of urinary cadmium concentration (U-Cd) based on a 22-year follow-up study after cessation of environmental Cd pollution. Spot urine samples were obtained from the inhabitants (32 men and 36 women) in the target area in 1986, 1991, 1999, 2003 and 2008. These inhabitants were divided into higher or lower baseline U-Cd group by the cut-off of 5 μg l(-1) or 5 μg g(-1) creatinine. Biological half-life of U-Cd was estimated using a linear mixed model adjusted for the baseline age. In the higher baseline U-Cd groups, the estimated half-life and 95% confidence intervals were 12.4 years (9.3-18.8 years) and 11.4 years (9.3-14.6 years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 16.0 years (13.0-20.7 years) and 20.4 years (16.6-26.2 years) in men and women, respectively. In the lower baseline U-Cd groups, biological half-life for unadjusted U-Cd in men was solely significant (23.4 years) and longer than the corresponding half-life in the higher baseline U-Cd group. The biological half-lives of U-Cd obtained in this study were identical with the values for U-Cd or total body burden determined by a different method.

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.

Objective: Percutaneous endoscopic gastrostomy has been widely adopted, and its use is increasing in Japan due to the rapid aging of society and promotion of medical care at home. Percutaneous endoscopic gastrostomy is performed in patients with a variety of underlying basic diseases. Therefore, a procedure that is safe and less burdensome for the patient is required. Material and methods: We studied a percutaneous endoscopic gastrostomy procedure that is both safe and less burdensome, in 260 patients undergoing gastrostomy in our department. The items studied were postoperative risk factors for fever, postoperative risk factors for elevated leukocyte count, and risk factors for C-reactive protein (CRP) elevation. Results: Serious complications were fewer with the three-point fixing method of the abdominal and gastric walls. Multivariate analysis indicated that the conventional Pull method was an independent risk factor for fever (P

Previous studies have shown that GFR estimated from serum creatinine (eGFRcr) is higher in smokers although the implications remain unclear. We aimed to clarify the associations of smoking with eGFRcys (GFR estimated from serum cystatin C) and eGFRcr, cys (the surmised most precise GFR estimate based on serum creatinine and cystatin C) in a working population.Cross-sectional observation in 1,587 male workers aged 25-64 years. For eGFRcr, JEQcr proposed by the Japanese Society of Nephrology (JSN) and jEPIcr by the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) modified for Japanese, and for eGFRcys, JEQcys proposed by JSN and EPIcys by CKD-EPI were calculated together with eGFRcr,cys of JEQaver (the average of JEQcr and JEQcys) and jEPIcr,cys by CKD-EPI modified for Japanese.Mean JEQcys was 95.1 mL/min/1.73 m(2) in contrast to 80.9 in JEQcr, with this difference considerable. Serum cystatin C was higher in smokers and obese subjects while serum creatinine was lower in smokers and slender subjects. JEQcys and EPIcys were lower in smokers while JEQcr and jEPIcr were higher in smokers adjusting for body mass index (BMI). eGFRcr,cys (JEQaver and jEPIcr,cys) did not differ between the never smokers and current smokers. eGFRcr,cys predicted by the equations composed of eGFRcr, BMI, and smoking habits showed a good accordance with calculated eGFRcr,cys.Either eGFRcr, eGFRcys or both were not reliable indicators of renal function in workers who smoked. The possibly more precise estimate of eGFRcr,cys could be predicted by eGFRcr, BMI and smoking in such a generally healthy population.

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.

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.

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

Objective This cross-sectional study investigated the associations between the serum thyroid-stimulating hormone (TSH) concentration and indices of obesity in middle-aged Japanese men and women. Methods The participants were 2,037 employees (1,044 men and 993 women; age, 36-55 yr) of a metal products factory in Japan. Clinical examinations were conducted in 2009. We obtained a medical history and anthropometric measurements (body weight, body mass index [BMI] and waist circumference) and measured the serum TSH concentrations. The anthropometric indices were compared across serum TSH quartiles. The associations were evaluated separately according to the smoking status in men. Results The mean body weight (kg), BMI (kg/m(2)) and waist circumference (cm) were 69.2, 23.7 and 83.2 in men and 55.3, 22.3 and 74.3 in women, respectively. Men with a higher TSH concentration had higher body weight and BMI values (p for trend=0.016 and 0.019, respectively), and these significant associations were observed even after adjusting for age, smoking status and other potential confounders. The TSH level was not associated with waist circumference. We found a significant interaction between the TSH level and the smoking status on body weight (p for interaction=0.013) and a significant association between the TSH level and body weight in nonsmokers, but not in current smokers. No significant associations were observed between the TSH level and the anthropometric indices in women. Conclusion Significant positive associations between the serum TSH concentration, body weight and BMI were detected in men only, and an interaction with the smoking status was observed for this association.

Background: Elevated serum gamma-glutamyltransferase (GGT) is predictive of various cardiovascular (CV) risk factors including chronic kidney disease (CKD). Elevated serum GGT has been recognized in smokers who are likely to develop CKD, but no study has focused on serum GGT and CKD in smokers. Objectives: The aim of this study was to clarify the associations between cigarette consumption, elevation of serum GGT and the development of proteinuria and CKD. Patients and Methods: A retrospective 6-year observational study was conducted on 2,603 male workers aged between 40 and 64 years. Incidences of proteinuria detected by dipstick and CKD defined by proteinuria and/or reduced estimated glomerular filtration rate (eGFR) measured in health check-ups were determined 6 years later for those who had been free of them at baseline. Results: Higher means of serum GGT in smokers than in nonsmokers at baseline, and a higher incidence of elevated serum GGT in smokers than in nonsmokers during the 6-year period were recognized only for alcohol consumers. Incidences of proteinuria and moderate or severe CKD which has a high risk of future renal failure or CV disease were higher in the subjects with greater cigarette consumption or a higher serum GGT level. Multiple logistic regression analyses adjusting for major CV risk factors showed a significant interactive effect between smoking and elevated serum GGT on the development of proteinuria and an additive effect of smoking and serum GGT on the development of high-risk CKD. Conclusions: Elevation of serum GGT in smokers, to a large extent, depends on the associated alcohol consumption. Elevated GGT in smokers plays at least a partial role in the development of CKD, mainly proteinuria, and the underlying mechanisms remain to be elucidated.

The aim of this study was to identify psychosocial work characteristics associated with long sick leave in a large population of male Japanese employees in multiple workplaces. We ex- amined various psychosocial work characteristics (job overload, job control, supervisor support, coworker support, support by family and friends, role ambiguity, role conflict, intragroup conflict and intergroup conflict) of employees in six factories at the base line. We then conducted a follow- up survey on the recorded long sick leaves of ≥30 continuous days taken by the employees due to any medical condition. We found 574 cases of long sick leave out of 15,531 subjects during an aver- age 5.07-yr follow-up. The results showed that high supervisor support was significantly associated with a decrease in the hazard ratio (HR) of long sick leave after adjustment for several confounding factors (95%CI; 0.69-0.97). High role ambiguity also tended to increase HR, but without reaching significance (95%CI; 0.99-1.41). The results suggest that supervisor support in the workplace may be important to reduce long sick leave in Japanese male employees.

The aim of this study was to estimate the benchmark dose (BMD) as the threshold limit level of the cadmium (Cd) concentration in rice for itai-itai disease and/or suspected disease; it was based on the data that previously evaluated the association for such diseases with the Cd concentration in rice by using a logistic regression model. From 1971 to 1976, a total of 2446 rice samples were analyzed across the 88 hamlets in the Jinzu river basin. The mean Cd concentration in rice in each hamlet was used as the index of external Cd exposure of the entire population of the hamlet. We employed the incidence of itai-itai disease and/or suspected disease obtained from the available 55 hamlets. As the threshold, the lower limit of the BMD (BMDL) of the Cd concentration in rice for itai-itai disease and/or suspected disease was estimated using a logistic model, setting the benchmark response at 1% or 2%. The estimated BMDLs of the Cd concentration in rice for itai-itai disease and/or suspected disease were 0.62-0.76 and 0.27-0.56 mg kg

Aims: To investigate the effects of shift work on increased alcohol intake associated with poor sleep quality. Methods: This cross-sectional survey evaluated the correlation between work schedule, poor sleep quality and heavy drinking among 909 factory workers aged 35-54 years in Japan. Subjects included 530 day workers, 72 shift workers who did not work at night and 290 shift workers who engaged in night work. Heavy drinking was defined as a mean volume of alcohol consumption exceeding 60 g/day. Results: Compared with other workers, night-shift workers who suffered poor sleep quality exhibited the highest frequency of heavy drinking (17.6%). Multiple logistic regression analysis demonstrated that compared with day workers with good sleep, night-shift workers who experienced poor sleep had more than twice the odds of heavy alcohol consumption (odds ratio 2.17 [95% confidence interval (CI), 1.20-3.93]). Shift workers who did not work at night and day workers with poor sleep were not at increased odds of heavy drinking. Conclusion: Shift workers who engage in night work may try to modify their health behavior to cope with sleep problems. Such modification may be a risk factor for heavy drinking. Language: en

Objective: This cohort study investigated the association between eating speed and the incidence of type 2 diabetes in middle-aged Japanese men. Materials/Methods: Participants were 2,050 male employees of a metal products factory in Japan. We measured self-reported categorical eating speed. The incidence of diabetes was determined in annual medical examinations over a 7-year period. The association between eating speed and the incidence of diabetes adjusted for multiple variables (age, family history of diabetes, smoking, alcohol drinking, habitual exercise, and presence of hypertension and hyperlipidemia) was evaluated using Cox proportional hazards models. Results: The prevalence of obesity (BMI ≥ 25 kg/m 2) across the categories of eating speed (slow, medium, and fast) was 14.6, 23.3, and 34.8%, respectively, and a faster eating speed was associated with a higher prevalence of obesity. During the study, 177 participants developed diabetes. Crude incidence rates (/1,000 person-years) across the three categories of eating speed were 9.9, 15.6, and 17.3, respectively. Multivariate-adjusted hazard ratios (95% CI) across the categories were 1.00 (reference), 1.68 (0.93-3.02), and 1.97 (1.10-3.55), respectively, and eating speed was associated with the risk of diabetes (p for trend = 0.030). After further adjustment for BMI, a significant association was not observed. Conclusions: Eating speed was associated with the incidence of diabetes. Since these associations were not significant after adjusting for BMI, eating speed may act via its effect on body weight. Eating speed is a controllable risk factor, and eating slowly could be an acceptable lifestyle intervention for the prevention of diabetes mellitus. © 2012 Elsevier Inc. All rights reserved.

To clarify the renal effects of cigarette smoking in a middle-aged occupational population because the effects have previously been demonstrated mainly in community populations that included many elderly people who are thought to be vulnerable to such effects.In 990 middle-aged men recruited from a chemical plant, proteinuria was measured by a dipstick method and the glomerular filtration rate was estimated (eGFR) using a formula proposed by the Japanese Society of Nephrology.Proteinuria was found in 4.6% of the current smokers and 1.5% of the never-smokers. It was found in 4.8% of the subjects having a Brinkman index (BI) of 400-599 and 6.3% of those having a BI of 600 or above. The odds ratio for proteinuria in them was 2.94 (CI: 1.01-8.55) and 3.61 (CI: 1.29-10.1), respectively, adjusting for possible confounders. The mean eGFR was higher in smokers than in nonsmokers throughout middle age up to 64 years. Normal but high eGFR was found in 6.7% of the current heavy smokers and subnormal eGFR in 5.7% of the largest cumulative cigarette consumers in contrast to 3.0% or less of the never-smokers. Proteinuria was found in 13.3% of the subjects showing subnormal eGFR, specifically in 16.7% of the smokers and 8.3% of the nonsmokers.Smoking causes proteinuria in working middle-aged men. Smokers tend to have a high eGFR, but those with subnormal eGFR showed proteinuria most frequently. Whether the high eGFR in smokers will eventually decrease and cause proteinuria remains an important focus for further studies.

Little is known about the relationship between the HOMA of insulin resistance (HOMA-IR) and the risk of cardiovascular events in Asian populations, which have lower levels of HOMA-IR than Western populations. Accordingly, we determined the predictive value of HOMA-IR for cardiovascular risk in a Japanese population that was apparently free of diabetes, addressing whether insulin resistance itself increases cardiovascular risk independently of other relevant metabolic disorders.We followed 2,548 non-diabetic men aged 35 to 59 years for 11 years. The hazard ratios for the incidence of cardiovascular events due to increased HOMA-IR were estimated using a Cox proportional hazards model that was adjusted for potential confounding factors.The multivariate-adjusted hazard ratio for cardiovascular events compared with the first quartile of HOMA-IR (or=0.66) was 1.07 (95% CI 0.44-2.64) for the second (HOMA-IR 0.67-1.01), 1.36 (0.56-3.28) for the third (HOMA-IR 1.02-1.51) and 2.50 (1.02-6.10) for the fourth quartile (HOMA-IRor=1.52). The hazard ratio associated with a one SD (0.61) increment in log-transformed HOMA-IR was 1.51 (1.13-2.02). A similar positive relationship was observed for coronary events and stroke. In addition, the relationship between HOMA-IR and cardiovascular risk was broadly similar in participants with and without hypertension, dyslipidaemia (elevated triacylglycerol and/or reduced HDL-cholesterol), abdominal obesity and current smoking.Increased HOMA-IR predicted subsequent cardiovascular events in non-diabetic Japanese men. The association was independent of traditional cardiovascular risk factors and other relevant metabolic disorders.

To investigate the cross-sectional association between organizational justice (i.e., procedural justice and interactional justice) and psychological distress or work engagement, as well as the mediating roles of other job stressors (i.e., job demands and job control, or their combination, effort-reward imbalance [ERI], and worksite support).A total of 243 workers (185 males and 58 females) from a manufacturing factory in Japan were surveyed using a self-administered questionnaire including the Organizational Justice Questionnaire, Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, K6 scale, Utrecht Work Engagement Scale, and other covariates. Multiple mediation analyses with the bootstrap technique were conducted.In the bivariate analysis, procedural justice and interactional justice were significantly and negatively associated with psychological distress; they were significantly and positively associated with work engagement. In the mediation analysis, reward at work (or ERI) significantly mediated between procedural justice or interactional justice and psychological distress; worksite support significantly mediated between procedural justice or interactional justice and work engagement.The effects of organizational justice on psychological distress seem to be mediated by reward at work (or ERI) while those regarding work engagement may be mediated by worksite support to a large extent, at least in Japanese workers.

金沢大学医薬保健研究域医学系, 金沢医科大学健康増進予防医学（公衆衛生学）, Aims This study investigated the relationship between waist circumference and the subsequent incidence of Type 2 diabetes and the association with insulin resistance and pancreatic B-cell function in relatively lean Japanese individuals. Methods The study participants were 3992 employees (2533 men and 1459 women, aged 35-55 years) of a metal-products factory in Japan. The incidence of diabetes was determined in annual medical examinations during an 8-year follow-up. We calculated age- and sex-adjusted hazard ratios (HRs) according to the sex-specific quintile of waist circumference at baseline. Differences in baseline insulin resistance [homeostatis model assessment (HOMA)-IR] and pancreatic B-cell function (HOMA-B) were compared between participants who developed diabetes and those who did not. Results During the follow-up, 218 participants developed diabetes. Age- and sex-adjusted HRs across the quintiles of waist circumference were 1.78, 1.00 (reference), 1.59, 3.11 and 3.30, respectively (P for trend, < 0.0001). The HR for the lowest quintile was significantly higher than that for the second quintile. Among participants with waist circumference of the lowest quintile, HOMA-B was lower in those who developed diabetes than in those who did not [33.1 (24.1-45.0) vs. 54.3 (37.9-74.6) median (interquartile range), P < 0.0001], but HOMA-IR did not differ between these groups. Conclusions There was a J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes in relatively lean Japanese individuals; lower pancreatic B-cell function may also increase the risk of diabetes in very lean Japanese people. © 2009 Diabetes UK.

Objectives: The purpose of this longitudinal study was to investigate the effects of burnout on risk factors for arteriosclerotic disease. Methods: Baseline data were collected from 442 male middle managers working for a manufacturing company in Japan. All participants had a physical health check-up and completed the Japanese Maslach Burnout Inventory-General Survey. We calculated the Japanese-specific cut-off points of the MBI-GS and applied "exhaustion +1" criterion to define subjects as healthy or burnout at baseline. Follow-up measures were collected 4-5 yr later for 383 middle managers. Changes in the subjects' waist circumference, body weight, body mass index (BMI), blood pressure, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, fasting blood sugar, fasting insulin, HOMA-R, and HbA1c over a time period of 4 to 5 yr were compared between the healthy and burnout groups. New cases of large waist circumference, high BMI, metabolic syndrome, hypertension, hypercholesterolemia, high triglycerides, low HDL cholesterol, high LDL cholesterol, and impaired fasting glucose were detected at follow-up. Results: Changes in waist circumference, body weight, and BMI were significantly greater in burned-out managers than in healthy managers. Furthermore, compared to other variables (age and health behaviors such as smoking), burnout was a significant explanatory variable. The odds ratio of the burnout group was 2.80 for hypercholesterolemia with statistical significance after adjusting for age. After adjusting for age, health behaviors, and baseline total cholesterol, the results were similar. Conclusions: Burnout, which results from prolonged exposure to chronic work stress, may be associated with risk factors for arteriosclerotic disease.

Objectives: Previous European studies reporting low procedural justice and low interactional justice were associated with increased health problems have used a modified version of the Moorman's Organizational Justice Questionnaire (OJQ, Elovainio et al., 2002) to assess organizational justice. We translated the modified OJQ into the Japanese language and examined the internal consistency reliability, and factor-based and construct validity of this measure. A back-translation procedure confirmed that the translation was appropriate, pending a minor revision. Methods: A total of 185 men and 58 women at a manufacturing factory in Japan were surveyed using a mailed questionnaire including the OJQ and other job stressors. Results: Cronbach alpha coefficients of the two OJQ subscales were high (0.85-0.94) for both sexes. The hypothesized two factors (i.e., procedural justice and interactional justice) were extracted by the factor analysis for men; for women, procedural justice was further split into two separate dimensions supporting a three- rather than two-factor structure. Convergent validity was supported by expected correlations of the OJQ with job control, supervisor support, effort-reward imbalance, and job future ambiguity in particular among the men. Conclusion: The present study shows that the Japanese version of the OJQ has acceptable levels of reliability and validity at least for male employees.

The aim of this study was to investigate the effects of shift work on nutrient intakes, including macronutrient intake and micronutrient intake, in a large sample size. The study population included 2,254 male manual workers, 20-59 yr of age, employed in a factory. A self-administered diet history questionnaire was used. The subjects were classified into 3 groups according to their work schedule: (i) fixed day workers; (ii) shift workers without midnight shifts; and (iii) shift workers with midnight shifts. The nutrient intakes of the groups were compared by age group. There was a significant difference in nutrient intakes between subjects aged 20-29 yr and those aged 30 yr and over. Among subjects aged 20-29 yr, the energy density value for saturated fat and the energy adjusted intakes of calcium, potassium, vitamin A, and vitamin B1 were the lowest among shift workers with midnight shifts. Among subjects aged 30 yr and over, the total energy intake was the highest among shift workers with midnight shifts; the difference was significant compared to fixed day workers. Shift workers with midnight shifts had the highest intake of cereals among subjects 30 yr of age and older. In conclusion, there were no significant differences in nutrient intakes between fixed day workers and shift workers without midnight shift. Shift work, particularly midnight shift work, affected nutrient intake. The impact of shift work on nutrient intakes differed by age and the type of shift work.

The present study examined the relationship between genetic combinations of the C1429T polymorphism in the G-protein beta-3 subunit (GNB3) gene and the A1330V polymorphism in the low-density lipoprotein receptor-related protein 5 (LRP5) gene and the risk of hypercholesterolaemia in Japanese workers. The present study included observations from 1997 to 2002 in 927 males and 662 females who were not hypercholesterolaemic on entry. The endpoint was the development of hypercholesterolaemia, defined as a total cholesterol levelor =240 mg/dl. The odds ratios for the combination of polymorphisms were calculated using pooled logistic regression analyses that incorporated other potential factors into the model. The odds ratios in males and females with GNB3/1429TT and LRP5/1330VV or AV genotypes were 4.17 compared to males with the 1429CT or TT and 1330AA genotypes and 3.53 compared to females with the 1429CC, CT or TT and 1330AA genotypes. Assuming these effects were a mere addition of two independent effects, the odds ratios for both GNB3/1429TT and LRP5/1330VV or AV were estimated to be 3.27 for males and 1.42 for females. Therefore, the synergic effects were shown to be 1.28 times in males (not significant) and 2.49 times in females (P0.05 by bootstrap method). These results provide clear evidence that the genetic combination has a synergic effect. This study indicates that the combination of GNB3/C1429T and LRP5/A1330V is a very useful marker for predicting the development of hypercholesterolaemia in the general Japanese population.

Objectives The aim of this cohort study was to investigate the effects of shift work on changes in parameters related to metabolic disturbances. Methods The study population included 1529 male blue-collar workers, aged 19–49 years at baseline, working in a sash and zipper factory in Japan. The participants were divided into four groups according to the work schedule at baseline, the end point being workers doing fixed daytime work in both years (day–day), workers who changed from shift work to fixed daytime work (shift–day), workers who changed from fixed daytime work to shift work (day–shift), and workers doing shift work in both years (shift–shift). The changes in body mass index (BMI), blood pressure, serum cholesterol, and glycosylated hemoglobin A1c over a period of 10 years were compared among the groups by work schedule. Results The age-adjusted mean increase in BMI was 1.03 kg/m 2 for the day–shift workers, and it was significantly larger than that of the day–day workers and shift–day workers. The shift–shift workers showed a significantly larger increase in BMI than the day–day workers. These tendencies remained after adjustment for age and all other confounding factors, such as BMI, smoking, drinking, and leisure-time physical activity at baseline. The increase in total cholesterol tended to be higher among the shift–shift workers and the day–shift workers, but there were no significant differences. Blood pressure and hemogrlobin A1c did not differ among the four groups. Conclusions Shift work is considered to be a risk factor for excess weight. However, no significant difference in the biomarkers was found between daytime workers and shift workers.

We examined the influence of the A1330V variant in the low-density lipoprotein receptor-related protein 5 gene on blood pressure in a large cohort of Japanese workers. This study used analysis of covariance in a multivariate general linear model to adjust for other potential factors such as age, body mass index, blood chemistry and lifestyle. The target subjects were 1440 males and 1169 females selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg or the use of antihypertensive medications. Genotype distributions for A1330V in hypertensive males (AA = 139(54.5%), AV = 101(39.6%), VV = 15(5.9%)) and females (AA = 48(63.2%), AV = 24(31.6%), VV = 4(5.3%)) were not significantly different from normotensive males (AA = 594(50.1%), AV = 488(41.2%), VV = 103(8.7%)) and females (AA = 568(52.0%), AV = 441(40.3%), VV = 84(7.7%)). Allele distributions were not significantly different in either sex. In males, analysis of covariance showed that the VV genotype was associated with a 2.5 mm Hg lower diastolic blood pressure and a 2.3 mm Hg lower mean blood pressure than the AA genotype. This study indicates that the 1330V allele is an independent factor for lower diastolic and mean blood pressure in Japanese males.