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Background: Healthy life expectancy (HLE) is a population health indicator that is widely used in developed countries, but little is known about its relationships with combinations of non-communicable disease risk factors. This study was conducted to examine HLE at age 65 years according to combinations of blood pressure levels, body mass index, smoking status, and diabetes mellitus (DM) in a Japanese population.Methods: In a nationwide cohort study (NIPPON DATA90), data on these risk factors were obtained from participants in 1990 through physical examinations, blood tests, interviews, and questionnaires. Subsequently, participants aged ≥65 years underwent surveys on activities of daily living in 1995 and 2000, and multistate life tables were used to calculate combination-specific HLEs and their 95% confidence intervals (CIs).Results: The study population comprised 6,569 participants (men: 2,797; women: 3,772) who were followed until 2010. HLE at age 65 years in men with grade II/III hypertension, obesity, current smoker status, and DM (HLE 12.9; 95% CI, 12.9–13.0 years) was 9.7 years shorter than men without these risk factors (HLE 22.6; 95% CI, 22.4–22.8 years). Similarly, HLE at age 65 years in women with grade II/III hypertension, obesity, current smoker status, and DM (HLE 16.2; 95% CI, 15.9–16.5 years) was 10.1 years shorter than women without these risk factors (HLE 26.3; 95% CI, 26.3–26.3 years).Conclusion: The large discrepancies in HLEs underscore the impact of non-communicable disease risk factors, which should be considered when formulating health interventions to improve HLE in Japanese older adults.

To estimate the average treatment effect of working past the current retirement age on the health of Japanese men. We used publicly available data from the National Survey of Japanese Elderly, extracting a sample of 1288 men who were 60 years or older. Survey respondents were followed-up for at most 15 years for the onset of four health outcomes: death, cognitive decline, stroke and diabetes. By using the propensity score method, we adjusted for the healthy worker effect by incorporating economic, sociodemographic and health data in the form of independent variables. By calculating the differences in times to a health outcome between those in employment and those not employed, we estimated the average treatment effects on health of being in paid work past retirement age. Compared with those not employed, those in employment lived 1.91 years longer (95% confidence interval, CI: 0.70 to 3.11), had an additional 2.22 years (95% CI: 0.27 to 4.17) before experiencing cognitive decline, and had a longer period before the onset of diabetes and stroke of 6.05 years (95% CI: 4.44 to 7.65) and 3.35 years (95% CI: 1.42 to 5.28), respectively. We also observed differences between employees and the self-employed: the self-employed had longer life expectancies than employees. In terms of years to onset of diabetes or stroke, however, we only observed significant benefits to health of being an employee but not self-employed. Our study found that being in employment past the current age of retirement had a positive impact on health.

Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment.Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.Conclusion: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

Background: Whether smoking is associated with worse quality of life (QoL) or not is relatively controversial. The current study is to investigate the relationship between smoking and subjective QoL in a long cohort study.Methods: The NIPPON DATA 90 project collected 8,383 community residents in 300 randomly selected areas as baseline data in 1990, administered four follow-up QoL surveys, and evaluated mortality statistics. We conducted multinomial logistic regression analysis to compare past smokers and current smokers to never smokers, with impaired QoL and mortality as outcomes.Results: In four follow-ups, QoL data was collected from 2,035, 2,252, 2,522, and 3,280 participants in 1995, 2000, 2005, and 2012, respectively. In the 1995 follow-up, current smoking at baseline was not associated with worse QoL. In 2000 and 2005 follow-ups, smoking was significantly associated with worse QoL (odds ratio [OR] 2.1; 95% confidence interval [CI], 1.33–3.36 and OR 2.29; 95% CI, 1.38–3.80, respectively). In the 2012 follow-up, smoking was not associated with QoL. Sensitivity analysis did not change the result significantly.Conclusion: In this study we found that baseline smoking was associated with worse QoL in long-follow-up.

Background: It has been reported that chronic inflammation may play an important role in the pathogenesis of several serious diseases and could be modulated by diet. Recently, the Dietary Inflammatory Index (DII®) was developed to assess the inflammatory potential of the overall diet. The DII has been reported as relevant to various diseases but has not been validated in Japanese. Thus, in the present study, we analyzed the relationship between DII scores and high-sensitivity C-reactive protein (hs-CRP) levels in a Japanese population. Methods: Data of the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010 (NIPPON DATA2010), which contained 2,898 participants aged 20 years or older from the National Health and Nutrition Survey of Japan (NHNS2010), were analyzed. Nutrient intakes derived from 1-day semi-weighing dietary records were used to calculate DII scores. Energy was adjusted using the residual method. Levels of hs-CRP were evaluated using nephelometric immunoassay. Multiple linear regression analyses were performed. Results: After adjusting for age, sex, smoking status, BMI, and physical activity, a significant association was observed between DII scores and log(CRP+1) (standard regression coefficient = 0.05, P < 0.01). Although it was not statistically significant, the positive association was consistently observed in almost all age-sex subgroups and the non-smoker subgroup. Conclusions: The current study confirmed that DII score was positively associated with hs-CRP in Japanese.

Background: Non-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population.Methods: A total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg/dL, 60–89 mg/dL, 90–119 mg/dL, 120–149 mg/dL, 150–179 mg/dL, 180–209 mg/dL, and ≥210 mg/dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age <65 and ≥65 years.Results: During the follow-up period, 433 deaths due to CVD were detected. Compared with a non-fasting TG of 150–179 mg/dL, non-fasting TG ≥210 mg/dL was significantly associated with increased risk for CVD mortality (HR 1.56: 95% CI, 1.01–2.41). Additionally, lower levels of non-fasting TG were also significantly associated with increased risk for fatal CVD. In participants aged ≥65 years, lower levels of non-fasting TG had a stronger impact on increased risk for CVD mortality, while higher levels of non-fasting TG had a stronger impact in those aged <65 years.Conclusion: In a general Japanese population, we observed a U-shaped association between non-fasting TG and fatal CVD events.

Background: Basic and instrumental activities of daily living (BADL and IADL, respectively) are known predictors of mortality. However, the relationship between higher-level functional capacity (HLFC) and mortality and related sex differences have rarely been investigated.Methods: A prospective population-based cohort study was conducted in 1,824 older residents (≥65 years) with independent BADL from 300 randomly selected areas in Japan from 1995, and the participants were followed up until 2010. Using the Cox proportional hazards model, the relationship between HLFC and mortality risk was investigated, with adjustment for possible confounders. HLFC was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Baseline data were collected using a questionnaire or by home-visit interviews.Results: During an average 12.2-year follow-up, all-cause death was observed in 836 (45.8%) participants. Impaired HLFC was significantly associated with mortality (hazard ratio [HR] 1.37; 95% confidence interval [CI], 1.13–1.65). Lower social role was significantly associated with higher mortality risk in men (HR 1.38; 95% CI, 1.13–1.68). Lower IADL and intellectual activity were significantly associated with higher mortality risk in women (HR 1.50; 95% CI, 1.15–1.95 and HR 1.46; 95% CI, 1.19–1.79, respectively). The relationship between HLFC and mortality risk showed a similar tendency among cardiovascular diseases, stroke, cancer, and pneumonia.Conclusion: Impaired HLFC was associated with a high risk of all-cause mortality among community-dwelling older people with independent BADL. In particular, social role in men and IADL and intellectual activity in women were associated with long-term mortality risk.

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

Background: We sought to investigate the optimal values of BMI for the lowest risk of all-cause death and whether the optimal BMI differs according to smoking status in large-scale pooled analysis of 13 Japanese cohorts. Methods: Data from 179,987 participants of 13 well-qualified cohort studies conducted throughout Japan were used for our analysis. A cohort-stratified Cox proportional hazard model was used. P values for interactions were calculated based on the cross product of BMI and age, sex, or smoking status. Results: In the entire study population, all-cause mortality risk was lowest when the BMI was 22.0–24.9 kg/m2. This was also the case for selected healthy participants (never smoked, baseline total cholesterol level ≥4.1 mmol/L; the first 5 years of follow-up data were excluded). No effect modification of age, sex, or smoking status was observed. Regardless of their BMI, never smokers always had a lower all-cause mortality risk than did current smokers even with an ideal BMI in terms of mortality risk. Conclusion: A BMI of 22–24.9 kg/m2 correlated with the lowest risk of mortality, regardless of whether all participants or selected healthy participants were analyzed. The fact that smoking was more strongly associated with mortality than obesity emphasizes the urgency for effective anti-smoking programs.

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