Metabolic Syndrome and the Increased Risk of Medically Certified Long-term Sickness Absence: A Prospective Analysis Among Japanese Workers.

BACKGROUND: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers. METHODS: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components. RESULTS: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. CONCLUSION: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Overtime Work and the Incidence of Long-term Sickness Absence Due to Mental Disorders: A Prospective Cohort Study.

BACKGROUND: Although previous research has focused on the association between long working hours and several mental health outcomes, little is known about the association in relation to mental health-related sickness absence, which is a measure of productive loss. We aimed to investigate the association between overtime work and the incidence of long-term sickness absence (LTSA) due to mental disorders. METHODS: Data came from the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). A total of 47,422 subjects were followed-up in the period between April 2012 and March 2017. Information on LTSA was obtained via a study-specific registry. Baseline information was obtained at an annual health checkup in 2011; overtime working hours were categorized into <45; 45-79; 80-99; and ≥100 hours/month. RESULTS: During a total follow-up period of 211,443 person-years, 536 people took LTSA due to mental disorders. A Cox proportional hazards model showed that compared to those with less than 45 hours/month of overtime work, those with 45-79 hours/month were at a lower risk of LTSA due to mental health problems (hazard ratio [HR] 0.63; 95% confidence interval [CI], 0.56-0.71) while those with overtime work of ≥100 hours/month had a 2.11 (95% CI, 1.12-3.98) times higher risk of LTSA due to mental health problems. CONCLUSION: Engaging in excessive overtime work was linked with a higher risk of LTSA due to mental health problems while the lower risk observed among individuals working 45-79 hours/month of overtime work might have been due to a healthy worker effect.

Diagnosis-specific Cumulative Incidence of Return-to-work, Resignation, and Death Among Long-term Sick-listed Employees: Findings From the Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away. METHODS: We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012-2013 among employees of 11 Japanese private companies (n = 1,209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis. RESULTS: During the 3.5-year period (follow-up rate: 99.9%), 1,014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00-F99) to 95.3% for circulatory diseases (I00-I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00-D48), of which the cumulative incidence of death reached 14.2% by 1.5 years. CONCLUSION: Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

Prediabetes, Diabetes, and the Risk of All-Cause and Cause-Specific Mortality in a Japanese Working Population: Japan Epidemiology Collaboration on Occupational Health Study.

OBJECTIVE: Prediabetes has been suggested to increase risk for death; however, the definitions of prediabetes that can predict death remain elusive. We prospectively investigated the association of multiple definitions of prediabetes with the risk of death from all causes, cardiovascular disease (CVD), and cancer in Japanese workers. RESEARCH DESIGN AND METHODS: The study included 62,785 workers who underwent a health checkup in 2010 or 2011 and were followed up for death from 2012 to March 2019. Prediabetes was defined according to fasting plasma glucose (FPG) or glycated hemoglobin (HbA1c) values or a combination of both using the American Diabetes Association (ADA) or World Health Organization (WHO)/International Expert Committee (IEC) criteria. The Cox proportional hazards regression model was used to investigate the associations. RESULTS: Over a 7-year follow-up, 229 deaths were documented. Compared with normoglycemia, prediabetes defined according to ADA criteria was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.53; 95% CI 1.12-2.09) and death due to cancer (HR 2.37; 95% CI 1.45-3.89) but not with death due to CVD. The results were materially unchanged when prediabetes was defined according to ADA FPG, ADA HbA1c, WHO FPG, or combined WHO/IEC criteria. Diabetes was associated with the risk of all-cause, CVD, and cancer deaths. CONCLUSIONS: In a cohort of Japanese workers, FPG- and HbA1c-defined prediabetes, according to ADA or WHO/IEC, were associated with a significantly increased risk of death from all causes and cancer but not CVD.

Smoking Cessation, Weight Gain, and the Trajectory of Estimated Risk of Coronary Heart Disease: 8-Year Follow-up From a Prospective Cohort Study.

INTRODUCTION: The effect of weight gain following smoking cessation on cardiovascular risks is unclear. We aimed to prospectively investigate the association of weight gain following smoking cessation with the trajectory of estimated risks of coronary heart disease (CHD). METHODS: In a cohort of 18 562 Japanese male employees aged 30-64 years and initially free of cardiovascular diseases, participants were exclusively grouped into sustained smokers, quitters with weight gain (body weight increase ≥5%), quitters without weight gain (body weight increase <5% or weight loss), and never smokers. Global 10-year CHD risk was annually estimated by using a well-validated prediction model for the Japanese population. Linear mixed models and piecewise linear mixed models were used to compare changes in the estimated 10-year CHD risk by smoking status and weight change following smoking cessation. RESULTS: During a maximum of 8-year follow-up, both quitters with and without weight gain had a substantially decreased level of estimated 10-year CHD risk after quitting smoking, compared with sustained smokers (all ps for mean differences < .001). The estimated 10-year CHD risk within the first year after cessation decreased more rapidly in quitters without weight gain than in quitters with weight gain (change rate [95% confidence interval, CI] -0.90 [-1.04 to -0.75] vs. -0.40 [-0.60 to -0.19] % per year, p < .0001). Thereafter, the estimated 10-year CHD risk in both groups increased at similar rates (change rate [95% CI] -0.07 [-0.21 to 0.07] vs. 0.11 [-0.09 to 0.30] % per year, p = .16, from year 1 to year 2; and 0.10 [0.05 to 0.15] vs. 0.11 [0.04 to 0.18] % per year, p = .80, from year 2 to year 8). CONCLUSIONS: In this population of middle-aged, Japanese male workers, smoking cessation greatly reduces the estimated 10-year risk of CHD. However, weight gain weakens the beneficial effect of quitting smoking in a temporary and limited fashion. IMPLICATIONS: To the best of our knowledge, this study is the first to examine the effect of weight gain following smoking cessation on the trajectory of the absolute risk of CHD. Our data imply that the benefits of cessation for reducing the absolute risk of CHD outweigh the potential risk increase due to weight gain, and suggest that in order to maximize the beneficial effects of quitting smoking, interventions to control post-cessation weight gain might be warranted.

Smoking and Long-Term Sick Leave in a Japanese Working Population: Findings of the Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan. METHODS: We followed 70 896 workers aged 20-59 years (60 133 males, 10 763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (ie, SL lasting ≥30 consecutive days). Cause-specific analyses were also conducted. RESULTS: A total of 1777 people took long-term SL during a follow-up of 307 749 person years. Compared with never-smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.32; 95% confidence interval [CI] = 1.19 to 1.48). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.44, 95% CI = 1.22 to 1.69), cancer (HR = 1.49, 95% CI = 1.10 to 2.01), cardiovascular disease (CVD; HR = 2.16, 95% CI = 1.31 to 3.55), and injuries/external causes (HR = 1.83, 95% CI = 1.31 to 2.58). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.38, 95% CI = 0.99 to 1.92). Low-intensity smoking (ie, 1-10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to injuries/external causes compared with never-smokers. CONCLUSION: In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term SL. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan. IMPLICATIONS: Our study contributes to the literature on the association between smoking and SL in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on SL given that there is growing evidence of an elevated health risk associated with low-intensity smoking.

Loss of Working Life Years Due to Mortality, Sickness Absence, or Ill-health Retirement: A Comprehensive Approach to Estimating Disease Burden in the Workplace.

BACKGROUND: While much effort has focused on quantifying disease burden in occupational health, no study has simultaneously assessed disease burden in terms of mortality and morbidity. We aimed to propose a new comprehensive method of quantifying the disease burden in the workplace. METHODS: The data were obtained from the Japan Epidemiology Collaboration on Occupational Health (J-ECOH) Study, a large-scale prospective study of approximately 80,000 workers. We defined disease burden in the workplace as the number of working years lost among the working population during a 6-year period (April 2012 to March 2018). We calculated the disease burden according to consequences of health problems (ie, mortality, sickness absence [SA], and ill-health retirement) and disease category. We also calculated the age-group- (20-39 and 40-59 years old) and sex-specific disease burden. RESULTS: The largest contributors to disease burden in the workplace were mental and behavioural disorders (47.0 person-years lost per 10,000 person-years of working years; ie, per myriad [proportion]), followed by neoplasms (10.8 per myriad) and diseases of the circulatory system (7.1 per myriad). While mental and behavioural disorders made a greater contribution to SA and ill-health retirement compared to mortality, the latter two disorders were the largest contributors to the disease burden in the workplace due to mortality. The number of working years lost was greater among younger versus older female participants, whereas the opposite trend was observed in males. CONCLUSIONS: Our approach is in contrast to those in previous studies that focused exclusively on mortality or morbidity.

Diabetes, prediabetes, and suicide deaths in a Japanese working population.

OBJECTIVE: To examine the association of diabetes and prediabetes with suicide deaths in a Japanese working population. METHODS: A nested case-control study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. During 8 years of follow-up, we identified 56 registered cases of suicide death that had information on fasting plasma glucose or glycated hemoglobin A1c at any health check-up during the past 3 years prior to suicide. For each case, we randomly selected five controls matched for age, sex, and worksite. We used the latest health check-up data for analysis. We defined diabetes status based on the American Diabetes Association criteria and used a conditional logistic regression model to investigate the association. RESULTS: Adjusted odds ratios and 95% confidence intervals for suicide death were 0.67 (0.32-1.41) and 3.53 (1.05-11.91) for prediabetes and diabetes, respectively, compared to normoglycemia. Similar results were obtained when diabetes status was exclusively defined by the fasting plasma glucose or glycated hemoglobin A1c level. CONCLUSION: Diabetes, but not prediabetes, was associated with a higher risk of suicide death, compared with normoglycemia, among a Japanese working population.

BMI and Medically Certified Long-Term Sickness Absence Among Japanese Employees.

OBJECTIVE: In contrast to the association between excess weight and sickness absence (SA), the association in relation to underweight has been under-researched. This study aimed to examine the effects of BMI at both extremes of its distribution on SA. METHODS: Data came from the Japan Epidemiology Collaboration on Occupational Health study of 77,760 workers aged 20 to 59 years (66,166 males, 11,594 females). Information was collected on medically certified long-term SA (LTSA) (i.e., SA lasting ≥ 30 consecutive days) from April 2012 to March 2017. A sex-specific Cox proportional hazards model was used to investigate the associations. RESULTS: Among males, both obesity (hazard ratio [HR] = 1.81, 95% CI: 1.50-2.17) and underweight (HR = 1.56, 95% CI: 1.23-1.96) were significantly associated with LTSA compared with normal weight. This U-shaped association between BMI categories and LTSA was observed both for mental and physical disorders. Among females, an elevated risk was observed among those with overweight (HR = 1.54, 95% CI: 1.16-2.05). CONCLUSIONS: In a cohort of the Japanese working-age population, both obesity and underweight were associated with a greater risk of LTSA in males. Future research should not overlook the excess risk of LTSA associated with underweight.

Trajectories of body mass index and waist circumference before the onset of diabetes among people with prediabetes.

BACKGROUND & AIMS: To investigate trajectories of body mass index (BMI) and waist circumference (WC) among prediabetic people who progressed to diabetes, people who remained with prediabetes, and those who returned to normoglycemia. METHODS: We used data from 22,945 prediabetic people who received an annual health checkup for up to eight years. The development of diabetes was defined using the American Diabetes Association criteria. People who did not progress to diabetes during the observation period were classified as 'remained with prediabetes' or 'returned to normoglycemia', based on their last health checkup data. Trajectories of BMI and WC were evaluated using linear mixed models for repeated measures, with adjustment for a wide range of covariates. RESULTS: During the study period, 2972 people progressed to diabetes, 4706 returned to normoglycemia, and 15,267 remained with prediabetes. People who progressed to diabetes had a larger increase in mean BMI from 7 years to 1 year prior to diagnosis, which was about three times that of people who remained with prediabetes (annual change rate, 0.20 [95% confidence interval; 0.15 to 0.24] vs 0.06 [0.04 to 0.08] kg/m2 per year, P < 0.001), regardless of their BMI levels at the initial health checkup. Among people who returned to normoglycemia, mean BMI remained almost the same over time (-0.04 [-0.09 to 0.002] kg/m2 per year), except for those with obesity (-0.16 [-0.28 to -0.05] kg/m2 per year). As for WC, the annual change rate among people who developed diabetes was about 7 times that of people who remained with prediabetes (0.38 [0.32 to 0.45] vs 0.05 [0.03 to 0.08] cm per year, P < 0.001). We also observed a constant mean WC over time among people who had no central obesity and later returned to normoglycemia (-0.02 [-0.06 to 0.03] cm per year), and an annual decrease in mean WC among those who had central obesity and later returned to normoglycemia (-0.40 [-0.47 to -0.32] cm per year). CONCLUSIONS: Our study provides strong evidence that avoiding weight gain could help prediabetic people minimize the risk of developing diabetes, regardless of whether they are obese. Losing weight could help obese people restore normoglycemia from a prediabetic state, whereas maintaining current weight may help nonobese people return to normoglycemia.

Obesity and risk of hearing loss: A prospective cohort study.

BACKGROUND & AIMS: The existing yet limited prospective studies reported conflicting results about obesity and hearing loss. We investigated the prospective association between obesity and hearing loss in a large-scale Japanese working population, as well as the association between metabolic phenotype and hearing loss. METHODS: The study included 48,549 employees aged 20-64 years and free of hearing loss at baseline. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression was used to investigate the risk of hearing loss associated with body mass index (BMI) and metabolic phenotype (based on a BMI of ≥25.0/<25.0 kg/m2 and presence/absence of ≥2 components of metabolic syndrome, except waist circumference). Baseline and updated information were obtained from annual health checkups. RESULTS: With a median follow-up of 7 years, 1595 and 3625 individuals developed unilateral hearing loss at 1 and 4 kHz, respectively. The adjusted hazard ratios (HR) for hearing loss at 1 kHz were 1.21 (1.08, 1.36) and 1.66 (1.33, 2.08) for those with BMI 25.0-29.9 kg/m2 and BMI ≥30.0 kg/m2, respectively, compared to individuals with BMI <25.0 kg/m2. For hearing loss at 4 kHz, the corresponding HRs were 1.14 (1.05, 1.23) and 1.29 (1.09, 1.52). Compared with metabolically healthy non-obese individuals, the adjusted HRs for hearing loss at 1 kHz were 1.19 (1.03, 1.39), 1.27 (1.01, 1.61), and 1.48 (1.25, 1.76) for unhealthy non-obese, healthy obese, and unhealthy obese individuals, respectively. For hearing loss at 4 kHz, the corresponding HRs were 1.13 (1.04, 1.25), 1.21 (1.04, 1.41), and 1.26 (1.12, 1.41). CONCLUSIONS: Overweight and obesity are associated with an increased risk of hearing loss, and metabolically unhealthy obesity may confer additional risk.

Smoking cessation after long-term sick leave due to cancer in comparison with cardiovascular disease: Japan Epidemiology Collaboration on Occupational Health Study.

In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval [CI]: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.

Association between anthropometric indices of obesity and risk of cardiovascular disease in Japanese men.

OBJECTIVES: We aimed to compare the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with risk of cardiovascular disease (CVD) among middle-aged working Japanese men. METHODS: A nested case-control study was performed among middle-aged male employees who underwent periodic health checkup. A total of 241 CVD cases were identified and matched individually on age, gender, and worksite with 1205 controls. Data on BMI, WC, WHtR, smoking, hypertension, diabetes, and dyslipidemia collected at 4 years before the event/index date were retrieved. Associations between BMI, WC, WHtR, and CVD risk were assessed by using conditional logistic regression models. RESULTS: The strength of the association of BMI, WC, and WHtR with CVD risk was similar. The smoking-adjusted odds ratio (95% confidence interval) for CVD was 1.60 (1.38-1.85), 1.53 (1.33-1.78), and 1.56 (1.35-1.81) for a 1 SD unit increase in BMI, WC, and WHtR respectively. After further adjustment for hypertension, diabetes, and dyslipidemia, these associations were attenuated but remained statistically significant. CONCLUSIONS: Measures of general (BMI) and abdominal (WC and WHtR) obesity were similarly associated with CVD in middle-aged Japanese men.

Associations of anemia and hemoglobin with hemoglobin A1c among non-diabetic workers in Japan.

AIMS/INTRODUCTION: We examined the association between hemoglobin A1c (HbA1c) and anemia, which was categorized into three groups according to mean corpuscular volume (MCV), as well as the association between hemoglobin in the non-anemic range and HbA1c. MATERIALS AND METHODS: We used the 2016 health checkup data from 36,422 workers without diabetes. Anemic people were divided into three groups based on MCV: <80, 80-90 and >90 fL. Non-anemic people were divided into four groups based on their hemoglobin levels. We carried out multiple linear regression models to estimate the means and 95% confidence intervals (CIs) of HbA1c. RESULTS: For men, 0.2% had anemia with MCV <80 fL, 0.5% had anemia with MCV 80-90 fL, 0.9% had anemia with MCV >90 fL and 98.4% had no anemia. For women, the corresponding values were 6.1, 6.4, 2.8 and 84.7%, respectively. The adjusted mean HbA1c (%) values for men with anemia with MCV <80, 80-90 and >90 fL were 5.67 (95% CI 5.60-5.74), 5.58 (95% CI 5.54-5.62) and 5.41 (95% CI 5.37-5.44), respectively. Among men without anemia, HbA1c (%) increased from 5.36 (95% CI 5.34-5.39) in those with hemoglobin ≥17.5 mg/dL to 5.45 (95% CI 5.45-5.46) in those with hemoglobin 13.0 to <14.5 mg/dL (P for trend <0.001). The HbA1c values were higher in men with anemia with MCV <80 fL or MCV 80-90 fL, but lower in men with MCV >90 fL, compared with non-anemic men with hemoglobin 13.0 to <14.5 mg/dL (All P < 0.001). Similar findings were observed in women. CONCLUSIONS: We observed elevated HbA1c among anemic people with MCV <80 fL or MCV 80-90 fL, and decreased HbA1c among anemic people with MCV >90 fL, suggesting that different types of anemia might influence HbA1c differently. In addition, non-anemic people with lower hemoglobin levels had higher HbA1c levels, suggesting that hemoglobin levels are in need of consideration when interpreting HbA1c values among non-anemic people.

Five-year cumulative incidence of overweight and obesity, and longitudinal change in body mass index in Japanese workers: The Japan Epidemiology Collaboration on Occupational Health Study.

OBJECTIVE: The present study aimed to estimate cumulative incidence of overweight and obesity and describe 5-year longitudinal changes in body mass index (BMI) in a large occupational cohort in Japan. METHODS: Participants were 55 229 Japanese employees, who were aged 20-59 years and attended at all subsequent annual health check-ups between 2009 and 2014. Mixed model analysis was performed to examine the effects of age and cohort by gender on BMI change, with age as a random variable. Cumulative incidence of overweight (23.0≤ BMI <27.5 kg/m2 ) and obesity (BMI ≥27.5 kg/m2 ) was calculated. Logistic regression analysis was used to estimate odds ratios for the incidence of overweight and obesity according to age group. RESULTS: The incidence of overweight and obesity was approximately double in men (28.3% and 6.7%, respectively) compared to women (14.3% and 3.9%, respectively).The incidence of obesity decreased with age in men, but did not differ according to age in women (P for trend: .02 and .89, respectively). Among overweight participants, the incidence of obesity was higher in women (18.9%) than men (14.5%) and decreased with advancing age (P for trend: <.001 in men and .003 in women). Mean BMI was higher in men than women in all age groups throughout the period. Younger cohorts tended to have a higher BMI change compared with older cohorts. CONCLUSIONS: In this Japanese occupational cohort, transition from overweight to obesity is higher in women than men, and the more recent cohorts had a higher change in mean BMI than the older cohorts.

Serum cholesterol levels preceding to suicide death in Japanese workers: a nested case-control study.

OBJECTIVE: To investigate the association between suicide death and serum cholesterol levels as measured at times close to suicide death. METHODS: We conducted a nested case-control study of 41 cases of suicide deaths and 205 matched controls with serum total cholesterol (TC) levels till 3 years before suicide death in a large cohort of Japanese workers. RESULTS: Individuals in the lowest versus highest tertile/predefined category of TC in a Japanese working population had a three- to four-fold greater risk of suicide death. Each 10 mg/dl decrement of average TC was associated with an 18% increased chance of suicide death (95% confidence interval, 2-35%). Similar results were found for TC levels at each year. CONCLUSION: These results suggest that a low serum TC level in recent past is associated with an increased risk of suicide death.

Smoking, Smoking Cessation, and the Risk of Hearing Loss: Japan Epidemiology Collaboration on Occupational Health Study.

INTRODUCTION: We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort. METHODS: The cohort study included 50195 employees, who were aged 20-64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss. RESULTS: During follow-up, 3532 individuals developed high-frequency hearing loss, and 1575 developed low-frequency hearing loss. The hazard ratio (HR) associated with current smokers was 1.6 (95% confidence interval [CI] = 1.5 to 1.7) and 1.2 (95% CI = 1.1 to 1.4) for high- and low-frequency hearing loss, respectively, as compared with never smokers. The risk of high- and low-frequency hearing loss increased with the number of cigarettes smoked per day (both p for trend <.001). The HR associated with former smokers was 1.2 (95% CI = 1.1 to 1.3) and 0.9 (95% CI = 0.8 to 1.1) for high- and low-frequency hearing loss, respectively. The analysis by quitting years showed a decline in risk of hearing loss after quitting smoking, even among those who quitted less than 5 years before baseline. CONCLUSIONS: Smoking is associated with increased risk of hearing loss, especially at the high frequency, in a dose-response manner. The excess risk of hearing loss associated with smoking disappears in a relatively short period after quitting. IMPLICATIONS: The prospective association between smoking and hearing loss has not been well studied. To the best of our knowledge, our study is the largest to date investigating the association between smoking and incident hearing loss. Our results indicate that smoking is associated with increased risk of hearing loss in a dose-response manner. Quitting smoking virtually eliminates the excess risk of hearing loss, even among quitters with short duration of cessation. These results suggest that smoking may be a causal factor for hearing loss, although further research would be required to confirm this. If so, this would emphasize the need for tobacco control to prevent or delay the development of hearing loss.

Smoking, Smoking Cessation, and Risk of Mortality in a Japanese Working Population　- Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: The effect of smoking on mortality in working-age adults remains unclear. Accordingly, we compared the effects of cigarette smoking and smoking cessation on total and cause-specific mortality in a Japanese working population. Methods and Results: This study included 79,114 Japanese workers aged 20-85 years who participated in the Japan Epidemiology Collaboration on Occupational Health Study. Deaths and causes of death were identified from death certificates, sick leave documents, family confirmation, and other sources. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards regression. During a maximum 6-year follow-up, there were 252 deaths in total. Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10-2.01), 1.79 (0.99-3.24), and 1.80 (1.02-3.19), respectively, in current vs. never smokers. Among current smokers, the risks of total, tobacco-related cancer, and CVD mortality increased with increasing cigarette consumption (Ptrend<0.05 for all). Compared with never smokers, former smokers who quit <5 and ≥5 years before baseline had HRs (95% CIs) for total mortality of 1.80 (1.00-3.25) and 1.02 (0.57-1.82), respectively. CONCLUSIONS: In this cohort of workers, cigarette smoking was associated with increased risk of death from all and specific causes (including CVD and tobacco-related cancer), although these risks diminished 5 years after smoking cessation.

Prediabetes and cardiovascular disease risk: A nested case-control study.

BACKGROUND AND AIMS: We aimed to examine the risk of cardiovascular disease (CVD) with persistent prediabetes during the last four years prior to a CVD event in a large occupational cohort in Japan. METHODS: We performed a nested case-control study using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 197 registered cases of CVD were identified and matched individually with 985 controls according to age, sex, and worksite. Prediabetes was defined as fasting plasma glucose 100-125 mg/dL and/or HbA1c 5.7-6.4%. Persistent prediabetes was defined as having prediabetes at years one and four prior to the onset/index date; persistent normoglycemia was similarly defined. Associations between prediabetes and CVD risk were assessed using conditional logistic regression models. RESULTS: Compared with people with persistent normoglycemia over the four years prior to the onset/index date, the unadjusted odds ratio (95% confidence interval) for CVD was 2.88 (1.56, 5.32) for people with persistent prediabetes. After adjusting for BMI, smoking, hypertension, and dyslipidemia assessed four years before the onset/index date, the association was slightly attenuated to an OR (95% confidence interval) of 2.62 (1.31, 5.25). Prediabetes assessed at single time points was also associated with an elevated risk of CVD, with multivariable-adjusted odds ratio (95% confidence interval) of 1.72 (1.12, 2.64) and 2.13 (1.32, 3.43) for prediabetes at one and four years prior to the onset/index date, respectively. CONCLUSIONS: Prediabetes is associated with an increased risk of CVD. Identification and management of prediabetes are important for the prevention of CVD.

Correction: Development of Risk Score for Predicting 3-Year Incidence of Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

[This corrects the article DOI: 10.1371/journal.pone.0142779.].