Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90 days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

PURPOSE: Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90 days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC (≥ 70 mg prednisolone or equivalent; PSL) in the initial 90 days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080 days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90 days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC ≥ 5 mg PSL/day had a significantly increased fracture risk in the stratum of 30-59 days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5 mg PSL/day) for 90 days in the initial 90 days of GC therapy had a significantly increased fracture risk. CONCLUSIONS: GC exposure in the initial 90 days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90 days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

Rapid reduction in fracture risk after the discontinuation of long-term oral glucocorticoid therapy: a retrospective cohort study using a nationwide health insurance claims database in Japan.

Increased fracture risk due to oral glucocorticoids (GCs) rapidly decreases with GC discontinuation. However, evidence for this is limited. We found that fracture risk decreased rapidly in the first year after GC discontinuation, while hip fracture risk remained higher than reference levels for about two years after GC discontinuation. PURPOSE: We investigated changes in fracture risk following discontinuation of long-term oral glucocorticoids (GCs) using Japan's nationwide health insurance claims database (NDBJ). METHODS: We identified patients aged ≥ 50 years who initiated GC therapy in 2012-2019. Those receiving ≥ 5 mg (prednisolone or equivalent, PSL)/day for ≥ 72 days in the initial 90 days of GC therapy were classified as the GC-exposure group, and those receiving < 5 mg PSL/day for < 30 days were classified as the reference group. Patients discontinuing GC after 90 days of GC therapy were classified as the GC-discontinuation group; all others were classified as the GC-continuation group. We tracked the incidence rates of hip and clinical vertebral fractures for up to 990 days, and assessed fracture risk after GC discontinuation by hazard ratios (HR) adjusted by inverse probability weighting using propensity scores for GC discontinuation. RESULTS: There was a total of 52,179 GC-discontinuation, 91,969 GC-continuation, and 43,138 reference group women, and 57,560, 93,736, and 33,696 men in the corresponding groups, respectively. According to adjusted HRs, incidence rates of fractures were significantly lower in the GC-discontinuation group than in the GC-continuation group in the initial 90 days after GC discontinuation and remained significant for 360 days, except for hip fracture in men. HRs for hip fractures remained significantly higher in the GC-discontinuation group compared to the reference group for 720 days post-discontinuation. CONCLUSION: Fracture risk declines rapidly in the first year after GC discontinuation, but vigilance is necessary as the increased risk persists for two years post-discontinuation.

Mushroom intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study (CIRCS).

It is uncertain whether dietary intake of mushrooms rich in dietary fibre and several antioxidants is associated with a lower risk of dementia. We sought to examine prospectively the association between mushroom intake and the risk of disabling dementia. We performed a prospective study involving 3750 people aged 40 to 64 years residing in three communities who participated in an annual cardiovascular risk survey from 1985 to 1999. Cases of incident disabling dementia were surveyed from 1999 to 2020. We calculated the hazard ratios (HR) and 95 % CI for incident total dementia according to mushroom intake among participants with or without a history of stroke. During a mean 16·0 years' follow-up in 3739 eligible participants, 670 people developed disabling dementia. For women, mushroom intake was inversely associated with the risk of total dementia and the association was confined to dementia without a history of stroke. The multivariable HR (95 % CI) for total dementia in women were 0·81 (0·62, 1·06) for mushroom intake of 0·1-14·9 g/d and 0·56 (0·42, 0·75) for mushroom intake above 15·0 g/d (Pfor trend = 0·003) compared with no intake. The corresponding HR (95 % CI) for dementia without a history of stroke were 0·66 (0·47, 0·93) and 0·55 (0·38, 0·79) (Pfor trend = 0·01). In men, no associations were observed between mushroom intake and the risk of disabling dementia. Among Japanese women, dietary mushroom intake was associated with a lower risk of disabling dementia.

Serum folate and risk of disabling dementia: a community-based nested case-control study.

PURPOSE: The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia). METHODS: We performed a nested case-control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. RESULTS: After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51-0.99), 0.76 (0.54-1.06), 0.70 (0.49-1.00), and 0.62 (0.43-0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke. CONCLUSION: In this nested case-control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals.

Relationship between Ikigai and longitudinal changes in serum HDL cholesterol levels: the Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: Having positive psychological well-being has been associated with serum high-density lipoprotein cholesterol (HDLC), but no longitudinal study to date has examined the association between Ikigai and serum HDLC. Therefore, we examined the association between Ikigai and change in serum HDLC over time using a cohort dataset spanning 2010-2018. METHODS: The study included 471 men and 776 women aged 40-74 years who underwent a cardiovascular examination in 2010 and were asked their levels of Ikigai. We combined "definitely yes" and "yes" as "with Ikigai" and recorded "a little" as "with a little Ikigai" and "no" as "without Ikigai". We measured serum HDLC using direct methods. The association between Ikigai and serum HDLC levels at baseline, and changes in this relationship during an eight-year period, were analyzed using linear mixed-effect models. RESULTS: At the baseline, relative to those without Ikigai, women with Ikigai had higher serum HDLC (baseline difference in those with a little Ikigai = 7.52 mg/dl, 95% confidence interval [CI]: 1.12 to 13.9 and in those with Ikigai = 8.11 mg/dl, 95% CI: 1.54 to 14.7). The difference in serum HDLC between women with and without Ikigai remained over the eight-year follow-up period. There were no similar Ikigai-associated differences in the serum HDLC of men. CONCLUSIONS: Women with Ikigai showed differences in serum HDLC that were observed at baseline and persisted over time.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

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 <60 or >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 <60 mL·min-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.

Longitudinal changes in cell-mediated immunity after varicella-zoster virus skin test in the general population; Shozu Herpes Zoster Study: SHEZ study.

Varicella-zoster virus-specific cell-mediated immunity has been associated with the onset and severity of herpes zoster (HZ), and the administration of the HZ vaccine enhanced the immunity. However, limited data is available on the duration of cell-mediated immunity enhancement by soluble antigen of varicella-zoster virus (VZV) skin test. A prospective, community-based cohort study was conducted in Shozu County, Kagawa Prefecture, Japan. Repeated VZV skin tests containing inactivated VZV antigen and blood tests were performed on 365 subjects aged 60 years and older at baseline, 1, 2, and 3 years later. The differential immunity indices of VZV over time for cell-mediated and humoral immunity were evaluated. VZV skin test reaction and ELISpot counts increased significantly at 1, 2, and 3 years later compared to the baseline. However, humoral immunity indices did not change materially over time. Soluble antigen by VZV skin test enhanced VZV-specific cell-mediated immunity, and it persisted for at least 1 year. In addition, the inoculation with inactivated antigens every year by VZV skin test continued to enhance VZV-specific cell-mediated immunity after 2 and 3 years.

Modifying Effect of Outdoor Recreational Activity on the Association Between Anger Expression and Cardiovascular Disease Risk: The Circulatory Risk in Communities Study.

OBJECTIVE: Outdoor recreational activity (ORA) has been suggested as a practical strategy for anger management to moderate the risk of cardiovascular disease (CVD). However, there is a lack of evidence pertaining to this topic. Our aim was to examine whether ORA modified the association between anger expression and the risk of CVD. METHODS: A community-based cohort study was conducted among 1877 Japanese individuals aged 40 to 79 years at baseline in 1997. The anger expression was measured using the Spielberger Anger Expression Scale. Stratified into low and high ORA (0 and ≥1 of the four behaviors), a Cox proportional hazards model was used to assess the anger expression-related risk of incident CVD (ischemic heart disease and stroke). RESULTS: We identified 76 incident CVDs during a median follow-up of 18.8 years. Among participants with low ORA, anger expression was associated with an increased risk of CVD, whereas no association was identified among those with high ORA. The standardized hazard ratios were 1.53 (95% confidence interval, 1.23-1.91) and 0.77 (0.51-1.15) among those with low and high ORA, respectively ( p for interaction = .004). Similar associations were observed regarding the risk of total and ischemic stroke, and ischemic CVD. CONCLUSIONS: We found an elevated risk of CVD associated with anger expression among participants with low ORA but not among those with high ORA, suggesting that ORA use may mitigate the association between anger expression and CVD risk.

Longitudinal trajectories of smoking status using 25 year annually-updated data and all-cause mortality followed over 30 years: A community-based prospective cohort study.

We aimed to evaluate the long-term risk of smoking for all-cause mortality according to smoking status trajectories using 25-year annually-repeated input, traced by group-based trajectory modeling with an extension to account for non-random participant attrition or truncation due to death. We examined 2682 men and 4317 women aged 40 to 59 years who participated in annual health checks for the community-based prospective cohort study, 1975-1984 enrollment in Japan. The main outcome measure was all-cause mortality (follow-up period: median 30.2 years in men and 32.2 years in women). We traced annual smoking trajectories, stratified by sex and smoking status at baseline. For smokers at baseline, we identified five trajectories in both sexes, with different patterns of smoking cessation (e.g., early quitters and lifelong smokers). We calculated HRs and 95% CI of all-cause mortality using Cox proportional hazards regression modeling adjusted for age, body mass index, alcohol intake, blood pressure category, dyslipidemia and glucose category. Compared with one-time-point-based smokers, trajectory-based lifelong smokers had an increased risk of all-cause mortality; HRs were 1.31 (95% CI, 1.18-1.46) in men and 1.26 (95% CI, 0.91-1.73) in women. Among community residents aged 40 to 59 years, 25-year-trajectory-based lifelong smokers had an approximately 30% increased risk for all-cause mortality compared to one-time-point-based smokers. Risk of all-cause mortality among smokers with earlier cessation varied materially. It is necessary to consider the trajectories of smoking status to clarify the long-term excess risk of smoking.

Association Between Changes in Alcohol Consumption Before and After the Great East Japan Earthquake and Risk of Hypertension: A Study Using the Ministry of Health, Labour and Welfare National Database.

BACKGROUND: The 2011 Great East Japan Earthquake has resulted in a nuclear accident, forcing residents of the surrounding areas to evacuate. To determine any association between excessive drinking and hypertension in the setting of disaster, we assessed whether the proportion of excessive drinkers increased and if post-disaster excessive drinking was a risk factor for hypertension. METHODS: This retrospective study assessed data from the Japanese National Database. Cumulative population data for Fukushima Prefecture (3,497,576 people) were analyzed by categorizing residents into four areas-evacuation, coastal, central, and mountainous-to calculate the proportion of excessive, heavy (equivalent to binge drinking), and at-risk drinkers for 2008-2017. The hazard ratios (HRs) for the incidence of hypertension for 2012-2017 were examined in association with changes in drinking status pre- and post-disaster, which included 136,404 people who received specific health checkups pre-disaster (2008-2010) and post-disaster (2011-2012). RESULTS: The proportion of excessive drinkers among women increased after the disaster in all areas examined. The association between excessive drinking and the incidence of hypertension was determined among men and women in all areas; it was stronger among women in the evacuation areas, with the sex- and age-adjusted HRs for the incidence of hypertension of 1.41 for pre-disaster excessive drinking, 2.34 for post-disaster excessive drinking, and 3.98 for pre- and post-disaster excessive drinking, compared with not excessive drinking pre- and post-disaster. CONCLUSION: Excessive drinking post-disaster may be associated with an increased risk of hypertension among men and women, especially among women in the evacuation areas.

Impact of Perceived Social Support on the Association Between Anger Expression and the Risk of Stroke: The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: Anger has been suggested as a risk factor for stroke. Perceived social support (PSS) may relieve anger, thus reducing the risk of stroke; however, evidence supporting this is limited. We aimed to examine whether PSS modifies the risk of stroke associated with anger expression. METHODS: A cohort study was conducted among 1,806 community residents aged 40-74 years who received a cardiovascular risk survey, including anger expression, in 1997. A Cox proportional hazards model was applied to the participants with low and high PSS to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the risks of total stroke and its subtypes based on total anger expression after adjusting for known stroke risk factors. RESULTS: The median follow-up duration was 18.8 years, with 51 incident strokes. Among the participants with low PSS, anger expression had a positive association with the total stroke risk: The multivariable HR per standard deviation increment of total anger expression was 1.43 (95% CI, 1.13-1.82). In contrast, no association was identified among those with high PSS. The corresponding HR was 0.83 (95% CI, 0.49-1.40), with a significant interaction between low and high PSS (P = 0.037). Similar associations regarding the risk of ischemic stroke were found. CONCLUSION: We found an increased risk of stroke associated with anger expression among the participants with low PSS, but not among those with high PSS. Our results suggest that PSS might mitigate the risk of stroke associated with anger.

Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study.

OBJECTIVES: It has been hypothesized that dietary fiber intake has a beneficial impact on prevention of dementia, but the epidemiological evidence is scant. We sought to examine whether dietary fiber intake is inversely associated with risk of dementia requiring care under the national insurance (disabling dementia). METHODS: The study setting was the Circulatory Risk in Communities Study, involving 3739 Japanese individuals aged 40-64 years at the dietary surveys (1985-99). Dietary fiber intake was estimated using the 24-hour dietary recall method. Incident disabling dementia was followed up from 1999 through 2020. Disabling dementia was further classified into that with or without a history of stroke. Hazard ratios of disabling dementia according to quartiles of total, soluble, and insoluble fiber intake were calculated using the Cox proportional hazards model. RESULTS: During a median 19.7-year follow-up, a total of 670 cases of disabling dementia developed. Dietary fiber intake was inversely associated with risk of dementia: the multivariate hazards ratios (95% confidence intervals) were 0.83 (0.67-1.04), 0.81 (0.65-1.02), and 0.74 (0.57-0.96) for individuals with the second, third, and highest quartiles of dietary fiber intake, respectively, as compared with the lowest quartile (P for trend = 0.03). The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke. As for fiber-containing foods, potatoes, but not vegetables or fruits, showed a similar association. CONCLUSIONS: Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population.

Sex- and age-specific impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus in the development of disabling dementia in a Japanese population.

BACKGROUND: Sex- and age-specific impacts of cardiovascular risk factors on the development of dementia have not been well evaluated. We investigated these impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus on the risk of disabling dementia. METHODS: The study participants were 25,029 (10,134 men and 14,895 women) Japanese aged 40-74 years without disabling dementia at baseline (2008-2013). They were assessed on smoking status (non-current or current), overweight/obesity (body mass index ≥25 kg/m2 and ≥30 kg/m2, respectively), hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or any antihypertensive medication use), and diabetes mellitus (a fasting serum glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, hemoglobin A1c ≥6.5% by the National Glycohemoglobin Standardization Program or glucose-lowering medication use) at baseline. Disabling dementia was identified as the level of care required ≥1 and cognitive disability grade ≥IIa according to the National Long-term Care Insurance Database. We used a Cox proportional regression model to estimate hazard ratios and 95% confidence intervals (95% CIs) of disabling dementia according to the cardiovascular risk factors and calculated the population attributable fractions (PAFs). RESULTS: During a median follow-up of 9.1 years, 1,322 (606 men and 716 women) developed disabling dementia. Current smoking and hypertension were associated with a higher risk of disabling dementia in both sexes, whereas overweight or obesity was not associated with the risk in either sex. Diabetes mellitus was associated with a higher risk only in women (p for sex interaction = 0.04). The significant PAFs were 13% for smoking and 14% for hypertension in men and 3% for smoking, 12% for hypertension, and 5% for diabetes mellitus in women. The total PAFs of the significant risk factors were 28% in men and 20% in women. When stratified by age, hypertension in midlife (40-64 years) was associated with the increased risk in men, while diabetes mellitus in later-life (65-74 years) was so in women. CONCLUSIONS: A substantial burden of disabling dementia was attributable to smoking, and hypertension in both sexes and diabetes mellitus in women, which may require the management of these cardiovascular risk factors to prevent dementia.

Relationships of habitual daily alcohol consumption with all-day and time-specific average glucose levels among non-diabetic population samples.

BACKGROUND: Alcohol consumption is a prevalent behavior that is bi-directionally related to the risk of type 2 diabetes. However, the effect of daily alcohol consumption on glucose levels in real-world situations in the general population has not been well elucidated. This study aimed to clarify the relationship between alcohol consumption and all-day and time-specific glucose levels among non-diabetic individuals. METHODS: We investigated 913 non-diabetic males and females, aged 40-69 years, during 2018-2020 from four communities across Japan. The daily alcohol consumption was assessed using a self-report questionnaire. All-day and time-specific average glucose levels were estimated from the interstitial glucose concentrations measured using the Flash glucose monitoring system for a median duration of 13 days. Furthermore, we investigated the association between all-day and time-specific average glucose levels and habitual daily alcohol consumption levels, using never drinkers as the reference, and performed multiple linear regression analyses after adjusting for age, community, and other diabetes risk factors for males and females separately. RESULTS: All-day average glucose levels did not vary according to alcohol consumption categories in both males and females. However, for males, the average glucose levels between 5:00 and 11:00 h and between 11:00 and 17:00 h were higher in moderate and heavy drinkers than in never drinkers, with the difference values of 4.6 and 4.7 mg/dL for moderate drinkers, and 5.7 and 6.8 mg/dL for heavy drinkers. Conversely, the average glucose levels between 17:00 and 24:00 h were lower in male moderate and heavy drinkers and female current drinkers than in never drinkers; the difference values of mean glucose levels were -5.8 for moderate drinkers, and -6.1 mg/dL for heavy drinkers in males and -2.7 mg/dL for female current drinkers. CONCLUSIONS: Alcohol consumption was associated with glucose levels in a time-dependent biphasic pattern.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

Risk of Herpes Zoster in Relation to Body Mass Index Among Residents Aged ≥50 Years: The Shozu Herpes Zoster Study.

BACKGROUND: The impact of body mass index on incidence of herpes zoster is unclear. This study investigated whether body mass index was associated with a history of herpes zoster and incidence during a 3-year follow-up, using data from a prospective cohort study in Japan. METHODS: In total, 12,311 individuals were included in the cross-sectional analysis at baseline, of whom 1,818 with a history of herpes zoster were excluded from the incidence analysis, leaving 10,493 individuals. Body mass index (kg/m2) was classified into three categories (underweight: <18.5; normal: 18.5 to <25; and overweight: ≥25). To evaluate the risk of herpes zoster, we used a logistic regression model for prevalence and a Cox proportional hazard regression model for incidence. RESULTS: Being overweight or underweight was not associated with herpes zoster prevalence at baseline. The multivariate hazard ratios of herpes zoster incidence for overweight versus normal-weight groups were 0.67 (95% confidence interval, 0.51-0.90) in all participants, and 0.57 (95% confidence interval, 0.39-0.83) in women, with no significant difference for men. CONCLUSION: Being overweight was associated with a lower incidence of herpes zoster than being normal weight in older Japanese women.

Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age.

OBJECTIVE: this study explored whether the modification of selected lifestyles is likely to increase life expectancy from middle age onwards, regardless of the presence of major comorbidities. METHODS: we examined a prospective cohort of 20,373 men and 26,247 women aged 40-80 years. Eight modifiable lifestyle factors were assessed: consumption of fruit, fish and milk, walking and/or sports participation, body-mass index, smoking status, alcohol consumption and sleep duration. Modifiable healthy lifestyle factors scored one point each, for a maximum of eight points. The impact of modifiable healthy lifestyle adoption on lifetime gain during the ages of 40-102 years was analysed. FINDINGS: during the median 21 years of follow-up, 8,966 individuals (3,683 men and 5,283 women) died. Life expectancy at 40 years (95% confidence intervals) for 7-8 health lifestyle points was 46.8 (45.6-48.1) and 51.3 (50.0-52.6) years for men and women, respectively. The potential impact of modifiable healthy lifestyle adoption on lifetime gain persisted over the age of 80 years or more, in individuals with ≥5 factors (P < 0.001), particularly older men. The benefits were more pronounced among patients with major comorbidities, such as cardiovascular disease, cancer, hypertension, diabetes, kidney disease and those with multimorbidity throughout all age categories. CONCLUSION: adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major comorbidities in each life stage since middle age. The findings imply the importance of improving the one's lifestyle for an increased lifespan, even among older patients and/or those with multimorbidity.

Effects of a laughter program on body weight and mental health among Japanese people with metabolic syndrome risk factors: a randomized controlled trial.

BACKGROUND: While there have been several intervention studies on the psychological effects of laughter, few have examined both the psychological and physical effects. This study investigates the effects of a laughter program on body weight, body mass index (BMI), subjective stress, depression, and health-related quality of life (HRQOL) among Japanese community-dwelling individuals using a randomized controlled trial with a waitlist. METHODS: Overall, 235 participants (37 men and 198 women) aged 43-79 years (mean 66.9, median 67.0) were randomized into laughter intervention and control groups (n = 117 and n = 118, respectively) to participate in a 12-week laughter program. Body weight, subjective stress, subjective well-being, and HRQOL were measured at the baseline, with a 12-week follow-up. The laughter program intervention's effects on these factors were analyzed using an analysis of covariance adjusted by age, sex, risk factors, medication, and area. Furthermore, Pearson's correlation and a general linear model analyzed the relationship between participants' BMI and psychological index changes. RESULTS: The comprehensive laughter program significantly improved the mean body weight (p = 0.008), BMI (p = 0.006), subjective stress (p = 0.004), subjective well-being (p = 0.002), optimism (p = 0.03), and physical component summary (PCS) scores of HRQOL (p = 0.04). A similar tendency occurred for the mean changes in BMI and subjective stress score by area, sex, and age. Moreover, there was a significant and negative correlation between the change in BMI and PCS change (p = 0.04). CONCLUSION: The comprehensive 12-week laughter intervention program, mainly comprising laughter yoga, significantly improved physical and psychological functions such as body weight, BMI, subjective stress, subjective well-being, and HRQOL among predominantly elderly Japanese community-dwelling individuals with metabolic syndrome risk factors. Moreover, PCS improved among participants who reduced BMI after the intervention. These results suggest that the laughter program may help reduce body weight in participants with metabolic syndrome risk factors by reducing stress and improving HRQOL and mental health factors, such as subjective well-being and optimism. TRIAL REGISTRATION: Registered with the University Hospital Medical Information Network Clinical Trials Registry UMIN-CTR000027145 on 27/04/2017.

Associations Between Occupational Status, Support at Work, and Salivary Cortisol Levels.

OBJECTIVE: The present study investigated associations between occupation, job stress, and salivary cortisol levels after psychological tasks. METHODS: We examined 766 (273 men and 493 women) healthy employed Japanese participants aged 21 to 68 years (mean age = 46.4 years, standard deviation = 8.5) with three types of occupation: manager, teacher, and general worker. The Brief Job Stress Questionnaire was used to evaluate participants' job stress levels, including job demand, job control, support from supervisors, and support from coworkers. Salivary cortisol levels were measured at pre-session, post-stressful tasks, and post-relaxation. All samples were assayed using an enzyme-linked immunosorbent assay test. Natural log transformation was applied before statistical analyses. A multiple regression analysis and a repeated measures analysis of covariance were conducted to test associations between occupation and salivary cortisol levels, adjusting for confounding factors. Statistical analyses were conducted separately for men and women. RESULTS: Among both men and women, general workers had higher cortisol levels than managers throughout the experimental session (men 0.6 µg/dL and 0.4 µg/dL, respectively; women 0.5 µg/dL and 0.4 µg/dL, respectively). Job control was positively associated with cortisol levels measured in all sessions, after adjusting for confounding factors (standardized beta 0.15, 0.21, and 0.18 for pre-session, post-stressful-tasks, and post-relaxation, respectively, all p < 0.05). Men with low support from coworkers had higher cortisol levels than those with high support through the sessions (0.6 µg/dL and 0.4 µg/dL, respectively). CONCLUSION: Socioeconomic disparity according to occupational status was related to cortisol levels in Japanese workers. Support from coworkers may be effective for reducing cortisol secretion in men.

The association of family history of herpes zoster and the risk of incident herpes zoster: the SHEZ Study.

BACKGROUND: We investigated whether family histories of herpes zoster (HZ) are associated with the risk of incident HZ in a Japanese population. METHODS: A total of 12,522 Japanese residents aged ≥50 years in Shozu County participated in the baseline survey between December 2008 and November 2009 (the participation rate = 72.3%). They were interviewed at baseline by research physicians regarding the registrants' history of HZ. A self-administered questionnaire survey was conducted to evaluate the potential confounding factors. 10,530 participants without a history of HZ were followed up to ascertain the incidence of HZ during 3-years follow-up until the end of November 2012 with Japanese nationals. We estimated hazard ratios (HRs) of incident HZ according to first-degree family histories using the Cox proportional hazard regression after adjusting for age, sex, and other potential confounding factors. RESULTS: Compared to no HZ history of each family member, a history of brother or sister was associated with a higher risk of incident HZ while histories of father and mother were not. The multivariable HR (95%CI) of incident HZ for a history of brother or sister was 1.67 (1.04-2.69). When comparing to no family histories of all first-degree relatives, the multivariable HRs (95%CIs) were 1.34 (0.77-2.34) for a history of brother or sister alone, but 4.81 (1.78-13.00) for a history of mother plus brother or sister. As for the number of family histories, the multivariable HRs (95%CIs) were 1.08 (0.76-1.54) for one relative (father, mother, or brother or sister) and 2.75 (1.13-6.70) for two or more relatives. CONCLUSION: Family histories of mother plus brother or sister and two or more first-degree relatives were associated with a higher risk of incident HZ.