AIM: Hypertension is a leading contributor to the global disease burden and mortality. Although various risk factors have been identified, the roles of psychosocial stress and stress-coping strategies in the development of hypertension remain unclear. This study examined the longitudinal association between having a stress-coping strategy and the incidence of hypertension in Japanese communities. METHODS: A prospective cohort study, a part of the Circulatory Risk in Communities Study, included 3668 participants (1359 men and 2309 women), aged 40-74 years, from three rural areas in Japan. Stress levels, the presence of a stress-coping strategy, and hypertension status were assessed annually from 2010 to 2018. Generalized linear mixed models were used to examine longitudinal associations of stress levels and stress-coping strategies with the incidence of hypertension, adjusting for potential confounding factors. Separate models were fitted to explore sex-specific associations. RESULTS: The presence of a stress-coping strategy was significantly associated with a lower incidence of hypertension at baseline in both women (OR = 0.21 and 95% confidence interval (CI): 0.11 to 0.38, p < 0.001) and men (OR = 0.33, 95% CI: 0.18 to 0.60, p < 0.001). This association persisted throughout the follow-up period for both sexes, although the association was not significant in men with high stress. CONCLUSIONS: Having a stress-coping strategy was associated with a lower incidence of hypertension in both sexes. These findings highlight the potential role of coping strategies in hypertension prevention.

BACKGROUND: Although several studies have examined the associations between apoptosis-related factors or growth factors and cardiovascular diseases, evidence on their prospective association with hemorrhagic stroke remains limited. METHODS: We conducted a nested case-control study within the large cohort of the Circulatory Risk in Communities Study in Japan. A total of 98 cases (60 intracerebral hemorrhage and 38 subarachnoid hemorrhage; 34 men and 64 women, aged 35 to 83 years at baseline) were included, along with 196 controls matched by age, sex, community, and year of sample collection. We measured serum levels of the soluble form of Fas and insulin-like growth factor-I among cases and controls. The odds ratios of total hemorrhagic stroke and its subtypes were calculated using conditional logistic regression analyses. RESULTS: The median follow-up period from baseline to onset was 7.0 years. The multivariable odds ratios (95% confidence intervals) of total hemorrhagic stroke associated with a 1-standard deviation increment of soluble Fas (2.3 ng/mL) and insulin-like growth factor-I (40.5 ng/mL) were 0.93 (0.66-1.32) and 0.61 (0.41-0.89), respectively. The inverse association with insulin-like growth factor-I levels was similar for subarachnoid hemorrhage and intracerebral hemorrhage: the respective multivariable odds ratios were 0.53 (0.28-0.98) and 0.62 (0.37-1.04). CONCLUSIONS: The present study identified an inverse association between insulin-like growth factor-I levels and the risk of hemorrhagic stroke.

AIM: Evidence regarding the association between heart failure and sarcopenia in middle-aged and older community-dwelling adults is scarce. This study aimed to examine the association between NT-proBNP levels and sarcopenia among community-dwelling adults aged 40-74 years. METHODS: This cross-sectional study was conducted based on the Circulatory Risk in Communities Study, which involved 1675 Japanese residents aged 40-74 years. Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, physical function, and lifestyle information were measured. Participants were categorized according to their NT-proBNP levels (< 55, 55-124, and ≥ 125 pg/mL). Multivariate-adjusted logistic regression models were used to calculate the odds ratios for low skeletal muscle mass, muscle strength, walking speed, maximal walking speed, and sarcopenia according to serum NT-proBNP levels. RESULTS: Among the analyzed participants, the prevalence was 22.6% for low skeletal muscle mass, 4.3% for low handgrip strength, 14.3% for low walking speed, 24.1% for low maximal walking speed, and 5.9% for sarcopenia. The multivariable odds ratios (95% confidence interval, p for trend) comparing the highest versus lowest groups of serum NT-proBNP levels were 1.63 (1.07-2.49, p < 0.01) for low skeletal muscle mass, 3.38 (1.70-6.73, p < 0.01) for low handgrip strength, 1.81 (0.96-3.40, p = 0.06) for low walking speed, 1.75 (1.03-2.97, p = 0.06) for low maximal walking speed, and 2.56 (1.07-6.14, p = 0.03) for sarcopenia. CONCLUSIONS: High serum NT-proBNP levels, which are a surrogate marker for heart failure, were associated with low physical function and sarcopenia.

BACKGROUND/OBJECTIVES: Low intake of B vitamins may increase dementia; However, epidemiological evidence, particularly for riboflavin (vitamin B₂), remains sparse. This study aimed to examine the association between dietary intakes of B vitamins (riboflavin, vitamin B6, vitamin B12, and folate) and the incidence of disabling dementia necessitating care under Japan's national insurance over a 15-year observation period. METHODS: As part of the Circulatory Risk in Communities Study, a prospective study involving a community-based cohort of 4171 Japanese individuals aged 40-69 years was conducted. Dietary intakes of B vitamins were estimated through a single 24-h dietary recall method. Disabling dementia was defined by the daily living disability status related to dementia based on the long-term care insurance system of Japan. Hazard ratios of disabling dementia were estimated using area-stratified Cox proportional hazard models. RESULTS: Over a median follow-up of 15.4 years, 887 cases of disabling dementia were identified. Riboflavin intake was inversely associated with the risk of disabling dementia; the multivariable hazard ratio for the highest versus lowest quartiles was 0.51 (95% CI 0.42-0.63; P for trend <0.001). A similar inverse association was observed for vitamin B6 and folate intakes, with multivariable hazard ratios of 0.80 (0.66-0.97; P for trend = 0.01) and 0.79 (0.65-0.96; P for trend <0.001), respectively. CONCLUSIONS: Our findings suggest that dietary intake of B vitamins, especially riboflavin, vitamin B6, and folate, is associated with a reduced risk of disabling dementia in Japanese individuals.

INTRODUCTION: Evaluating long-term trends for the incidence of intracerebral hemorrhage is a priority for primary prevention. It is also important to assess the trends in the proportions of bleeding sites because the pathogenesis, prognosis, and operative procedures differ among them. METHODS: A prospective community-wide stroke registry in two rural Japanese communities (Ikawa Town and Kyowa Town, with populations of approximately 5000 and 15,000, respectively) was conducted. The age-adjusted incidence of intracerebral hemorrhage from 1985 to 2017 was calculated by the direct method using the World Standard Population. The proportions of intracerebral hemorrhage by bleeding sites (putamen, thalamus, lobes, cerebellum, and brainstem) based on neuroimaging were calculated in each of the following three periods: 1985-1995, 1996-2006, and 2007-2017. RESULTS: During the study period, 383 intracerebral hemorrhage events as first-ever strokes were registered. The age-adjusted incidence declined over time by 33%, with a large reduction between 1985-1989 and 1990-1994, but the magnitude of the decline has diminished since the 1990s. The proportions of bleeding sites were 37%, 29%, and 31% for putamen in 1985-1995, 1996-2006, and 2007-2017, respectively; the corresponding proportions were 24%, 35%, and 18% for thalamus; 10%, 10%, and 21% for lobes; 2%, 8%, and 12% for cerebellum; and 8%, 6%, and 5% for brain stem. CONCLUSION: The age-adjusted incidence declined by 33% from the 1990s with a large reduction in the early 1990s in Japanese rural communities. Among intracerebral hemorrhages, the proportion of bleeding sites decreased for the putamen, thalamus, and brain stem, and increased for lobes and the cerebellum.

AIM: Preventing frailty is crucial; however, the current evidence is limited to findings from older adults and may not apply to earlier life stages. This study examined the associations between health screening findings, body mass index, lifestyle factors, and medical findings in midlife with frailty in older ages by longitudinal analysis and the associations between them in older ages by cross-sectional analysis. METHODS: The study was conducted in a population-based cohort of the Circulatory Risk in Communities Study. We used the data of 1785 men and women aged 40-65 years (mean age: 54 years) who underwent health examinations between 2002 and 2004 in two Japanese communities. Among them, the frailty evaluation was conducted for 784 men and women aged 60 years or older (average age: 69 years) between 2017 and 2019. Multinomial logistic regression analysis was performed to calculate the multivariable odds ratios of pre-frailty and frailty compared with non-frailty, based on body mass index, lifestyle factors, and medical findings in midlife using longitudinal data, and based on these factors in older ages using cross-sectional data. RESULTS: We identified 351 non-frailty, 400 pre-frailty, and 33 frailty cases according to Fried's phenotype. Being overweight in middle age was associated with frailty in older ages in the longitudinal analysis, while being overweight in older ages was not in the cross-sectional analysis. A history of musculoskeletal disorders in both midlife and older ages was associated with frailty. In the cross-sectional analysis but not in the longitudinal analysis, the factors associated with pre-frailty or frailty included current smoking, current drinking, exercise, consumption of vegetables and soy products, and diabetes mellitus. CONCLUSIONS: Being overweight in midlife was associated with frailty in older ages, pointing to the importance of keeping an appropriate weight and lifestyle modifications in midlife to prevent frailty. Geriatr Gerontol Int 2025; ••: ••-••.

BACKGROUND: Previous research on the relationship between alcohol and stroke has highlighted several issues. Notably, the conventional categorization based on average consumption, which categorizes both those who consume 20 g/day of alcohol daily and those who engage in risky single-occasion drinking (RSOD) only on weekends into low drinkers, makes it difficult to account for individuals who fall into distinct characteristics. This study examined the association between alcohol and stroke, accounting for both average drinking levels and RSOD occurrences. METHODS: In a community-based prospective cohort study in Japan, 8026 men and 12,461 women were followed from 1989 to 2018. The outcome was the first-ever stroke event during the follow-up period. Alcohol consumption was divided into seven categories: never drinkers; former drinkers; low drinkers (<20 g/day on average for men and <10 g/day for women) without RSOD; moderate drinkers (20-59 g/day on average for men and 10-39 g/day for women) without RSOD; low drinkers with RSOD; moderate drinkers with RSOD; and heavy drinkers (≥60 g/day on average for men and ≥40 g/day for women). RSOD was defined as consuming ≥60 g for men and ≥40 g for women on a single occasion. We calculated sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stroke across these drinking categories compared with never drinkers. RESULTS: Low-to-moderate drinkers with RSOD experienced a significantly higher hazard of stroke; the multivariable HR (95% CI) of 1.47 (1.01-2.13) among men and 3.41 (1.50-7.79) among women. Overall, although some were not significant, low-to-moderate drinkers with and without RSOD tended to be associated with a higher hazard of stroke, except for low drinkers with RSOD in women. CONCLUSIONS: RSOD potentially increases the risk of stroke among men and women, even if their usual amount of alcohol consumption is low to moderate.

BACKGROUND: Few studies have prospectively, comprehensively, and by sex, examined the relationship between lifestyle and depressive symptoms. This study aimed to longitudinally examine which lifestyle factors are associated with depressive symptoms in a large cohort of Japanese participants stratified by sex. METHODS: Among 9087 office and community-based residents who attended a health measurement course at the Osaka Medical Center for Health Science and Promotion between 2001 and 2002, 6629 individuals (3962 men and 2667 women) without prior depressive symptoms were followed until the end of March 2012 to observe the associations between lifestyle factors and the development of new depressive symptoms. RESULTS: During the 5.06-year follow-up, 913 participants (517 men and 397 women) developed new depressive symptoms. Lifestyle factors such as very low physical activity, short sleep duration, smoking, skipping breakfast, and consuming a high-fat, high‑sodium diet, were associated with increased hazard ratios for depressive symptoms. Conversely, regular exercise, stress-coping methods, and diets rich in fish and fruit were associated with a reduced risk of depressive symptoms. In men, the risk was increased by very low physical activity, smoking, and diets including sugar-sweetened drinks, fatty meats, noodle soups, and highly seasoned dishes. In women, the risk was increased by long working hours and decreased by diets including seafood and fruits. CONCLUSIONS: Sex-specific differences were observed in the relationship between lifestyle and the onset of depressive symptoms. Alongside shared factors, such as sleep and stress management, sex-specific strategies could enhance prevention.

BACKGROUND: Quick accomplishment and responsiveness are behaviors related to time management by perceived control of time, such as a positive feeling of using one's time well. In recent years, positive psychological states have been associated with a lower risk of cardiovascular disease (CVD). Thus, we investigated the associations of quick accomplishment and responsiveness with CVD mortality in a large cohort study. METHODS: The study participants were 75,049 (30,901 men and 44,148 women) aged 40-79 between 1988 and 1990 and followed until the end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality from CVD according to quick accomplishment, responsiveness, and their combination were calculated after adjustment for potential confounding factors using the Cox proportional hazard model. RESULTS: Quick accomplishment was associated with a lower risk of CVD mortality in women; a similar but marginally significant association was observed in men; the respective multivariable HR (95%CI) was 0.91 (0.83-0.99) and 0.93 (0.86-1.01). The presence of both quick accomplishment and responsiveness was associated with lower risk in men, which was confined to men aged 60-79; the respective multivariable HR (95%CI) was 0.88 (0.78-0.99) and 0.83 (0.72-0.96). CONCLUSIONS: Quick accomplishment was associated with a lower risk of CVD mortality. Quick accomplishment and responsiveness combined were inversely associated with CVD mortality risk among older men.

UNLABELLED: 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.

Background: Evaluating the risk factors for intracerebral hemorrhage is indispensable for primary prevention. However, the pathogenesis varies depending on the bleeding site, and few prospective studies have explored risk factors in detail for each site. Participants and methods: The Japan Public Health Center-based Prospective Study is a prospective study comprising a population-based sample of Japanese adults in 1990 (Cohort I) and in 1993 (Cohort II). A total of 34,137 participants (11,907 men and 22,230 women) were enrolled in this study and followed up until 2009 for Cohort I and until 2012 for Cohort II. The association between risk factors (age, sex, blood pressure, serum cholesterol, triglycerides, blood glucose, body mass index, smoking, and drinking status) and intracerebral hemorrhage by its bleeding site (lobes, putamen, thalamus, cerebellum, and brainstem) was assessed using Cox proportional hazards analysis. Results: During a median 20-year follow-up, 571 intracerebral hemorrhage events occurred. Hypertension was associated with an increased risk of total intracerebral hemorrhage, but not lobar hemorrhage. The multivariable hazard ratio (95% confidence intervals) was 2.09 (1.75–2.50) for total intracerebral hemorrhage. In contrast, a low serum total cholesterol level was associated only with lobar hemorrhage (1.73 (1.01–2.96)). Heavy drinking was associated with the risk of total and putamen hemorrhage, and obesity was associated with the risk of putamen hemorrhage. Discussion and conclusion: The present study identified different risk factors depending on the bleeding site of intracerebral hemorrhage.

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.

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.

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.

Low back and knee pain, as major symptoms and early signs of osteoarthritis, have restricted healthy life expectancy, and numerous guidelines have recommended therapeutic exercise as the first-line treatment for chronic pain. Proportions of medical and exercise consultation use for those pain have been unclear, and these may change in the future. We performed a cross-sectional study of 2,954 persons aged over 30 years in 2017 as a part of the Circulatory Risk in Communities Study. A generalized linear model with logit link and 11-year age-group moving averages were used to estimate sex- and age-specific average proportions of lifetime pain, chronic pain, and dysfunctional chronic pain of the low back and knee, and history of medical and exercise consultation use. The medical consultation use increased in the order of lifetime pain, chronic pain, and dysfunctional chronic pain, reaching 69.1 % [65.2, 72.8] in women and 74.9 % [70.3, 79.0] in men for chronic low back pain, and 70.3 % [66.1, 74.2] in women and 55.6 % [49.3, 61.7] in men for chronic knee pain. On the other hand, the exercise consultation use accounted for 36.5 % [32.6, 40.6] in women and 28.8 % [24.4, 33.5] in men for chronic low back pain, and 40.8 % [36.5, 45.2] in women and 20.6 % [16.0, 26.0] in men for chronic knee pain. This survey revealed the differences in the multilayer proportions of medical and exercise consultation use for low back and knee pain in the cardiovascular mass screening, suggesting exercise consultation was less often provided compared to medical consultation.

AIM: Anger expression is associated with an increased risk of cardiovascular disease. This positive association was confined to individuals with lower perceived social support and outdoor recreational activity. However, the effects of retirement status remain unclear. This study aimed to investigate whether retirement status after the age of 60 years modifies the association between anger expression and the risk of cardiovascular disease in the Japanese population. METHODS: This longitudinal study included 499 community-dwelling retired and employed workers aged 60-79 years, who completed a cardiovascular risk survey in 1997. A Cox proportional hazards model was used to estimate the hazard ratios and 95% confidence intervals of incident cardiovascular disease (ischemic heart disease and stroke) according to anger expression in retired and employed workers after adjusting for potential cardiovascular risk factors. RESULTS: A total of 37 participants experienced incident cardiovascular disease during the mean follow-up period of 14.8 years (standard deviation 5.5 years). In retired workers, anger expression was associated with an increased cardiovascular disease risk, whereas no such association was observed in employed workers. The respective hazard ratio per one-standard deviation increment of total anger expression was 1.77 (95% confidence interval 1.29-2.43) and 1.03 (95% confidence interval 0.64-1.66; P for interaction = 0.036) among retired and employed workers, respectively. CONCLUSIONS: A positive association between anger expression and the risk of cardiovascular disease was confined to retired workers, suggesting that continuing work after retirement age could reduce anger expression-related cardiovascular disease risk. Geriatr Gerontol Int 2024; ••: ••-••.

AIM: Less is known about the impact of supper time on cardiovascular disease (CVD) risk among hypertensives and nonhypertensives. We aimed to explore this issue in a cohort study. METHODS: We analyzed the data of 72,658 participants (15,386 hypertensives and 57,272 nonhypertensives) aged 40-79 years without a history of CVD at baseline (1988-1990) under the Japan Collaborative Cohort study. Supper time was assessed based on self-reported questionnaires categorized as before 17:00, between 17:00 and 20:00, after 20:00, irregular supper time, and reference supper time (17:00-20:00). Hazard ratios (HRs) and 95% confidence intervals (95% CI) of CVD mortality were calculated according to supper time after adjustment for potential confounders, stratified by hypertensive status and age group (＜65 and ≥ 65 years). RESULTS: During a median of 19.4 years of follow-up, 4,850 CVD deaths were recorded. Compared with the reference time, the risk of CVD mortality was higher for irregular supper time for the total population, either hypertensives or nonhypertensives, more specifically hypertensives aged ≥ 65 years; the multivariable HR (95% CI) of CVD mortality in the total population was 1.28 (1.11-1.50, P＜0.01). The supper time of ＞20:00 tended to be associated with the higher risk only for hypertensives; the multivariable HR was 1.39 (0.98-1.96, P=0.06). CONCLUSION: Irregular supper time was associated with an increased risk of CVD mortality. Supper timing could be a surrogate marker for CVD risk.

BACKGROUND AND AIMS: We aimed to examine the association between timing of clinic visits after health checks and risk of hospitalization for cardiovascular events and all-cause mortality among the high-risk population. METHODS: A total of 412,059 high-risk individuals from the health claims database of the Japan Health Insurance Association were divided into 4 groups according to the timing of clinic visits during 12 months after health checks (early: <3 months, intermediate: 4-6 months, late: 7-12 months, and none). Cox proportional hazard regression models were used to examine the associations between timing of clinic visits after health checks and risk of hospitalization for stroke, coronary heart disease, heart failure, or all-cause mortality. RESULTS: During a median follow-up of 4.3 years, we identified a total of 15,860 cases having composite outcomes of first hospitalization for stroke, coronary heart disease, heart failure, or all-cause mortality. Compared to high-risk adults without clinic visits after the health checks, the fully adjusted hazard ratios (95% confidence interval) of a composite outcome were 0.78 (0.74, 0.81), 0.84 (0.78, 0.89), and 0.94 (0.89, 1.00) for early, intermediate, and late clinic visits, respectively. Compared to no clinic visit, an early clinic visit was associated with lower risks of all individual endpoints, and the risk reductions appeared to be greater in the hospitalization for stroke and heart failure. CONCLUSIONS: The present study using real-world data provided evidence that an early clinic visit after health checks was associated with lower risks of hospitalization for major cardiovascular events and all-cause mortality among high-risk individuals.

Cardiovascular diseases (CVDs), such as heart disease and stroke, have a significant impact on life expectancy, healthy life expectancy, and medical costs in Japan. Each prefecture is currently promoting measures in accordance with the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease, which was established by the government. In recent years, the crude mortality rate of heart disease in Japan has been increasing year by year with the aging population. Meanwhile, the age-adjusted mortality rate has leveled off or shown a downward trend. In addition, the proportion of acute myocardial infarction has decreased, whereas the proportion of heart failure has increased. By contrast, both the crude and age-adjusted mortality rates of stroke have a declining trend. Nevertheless, considering the potential variations in death certificates issued for patients with myocardial infarction across different prefectures, it is crucial to determine the incidence of CVD in each prefecture for the accurate assessment of CVD trends. However, as for the incidence of CVD, not many prefectures have yet implemented registration programs. The age-adjusted incidence rate of acute myocardial infarction has been increasing in some areas and decreasing in others since 1990. The age-adjusted incidence rate of stroke has consistently declined since the 1960s. Nevertheless, the possible increase in the incidence rate of cerebral embolism and thrombotic cerebral infarction among patients with different stroke subtypes is a cause of concern. The impact of heart failure on the incidence of heart disease has increased. Therefore, relevant academic societies and prefectures must collaborate in registering the incidence of heart failure as well as myocardial infarction and implementing countermeasures.

Immunity is known to persist after vaccination for varicella zoster virus, but the duration of immunity in patients who develop herpes zoster (HZ) remains unknown. To investigate the association between a past history of HZ and its occurrence in the general population. The Shozu HZ (SHEZ) cohort study included data for 12 299 individuals aged ≥50 years with information on their HZ history. Cross-sectional and 3-year follow-up studies were carried out to analyze the associations between a history of HZ (yes <10 years, yes ≥10 years, no) and the proportion of positive varicella zoster virus skin test results (erythema diameter ≥5 mm) and the risk of HZ after adjusting for potential confounding factors including age, sex, body mass index, smoking status, sleep duration, and mental stress. The incidences of positive skin test results were 87.7% (470/536) for individuals with a history of HZ <10 years ago, 82.2% (396/482) for those with a history of HZ ≥10 years, and 80.2% (3614/4509) for those with no history of HZ. The multivariable odds ratios (95% confidence intervals) of erythema diameter ≥5 mm were 2.07 (1.57-2.73) and 1. 39 (1.08-1.80) for individuals with a history <10 years and ≥10 years ago, respectively, compared with no history. The corresponding multivariable hazard ratios of HZ were 0.54 (0.34-0.85) and 1.16 (0.83-1.61), respectively. A past history of HZ <10 years ago may reduce the occurrence of HZ.

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.

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.

AIM: A cluster randomized trial was conducted within 41 Japanese municipalities (21 intervention and 22 usual care) to examine whether the standardized health counseling for individuals at high cardiovascular risk screened at community sites accelerates clinic visits to strengthen the primary health care system. METHODS: Among high-risk individuals aged 40-74 years screened by health checkups, 8,977 and 6,733 were allocated to the intervention and usual care groups, respectively, who were not under medical treatment but had high levels of blood pressure (systolic/diastolic ≥ 160/100 mmHg), hemoglobin A1c or glucose (≥ 7.0% or corresponding glucose levels), LDL-cholesterol (≥ 180 mg/dL for men), and/or proteinuria of ≥ 2+. The intervention was performed from May 2014 to March 2016 under a standardized health counseling program based on the health belief model primarily by public health nurses. The usual care group was provided with local counseling protocols. RESULTS: The cumulative proportions of clinic visits for 12 months after health checkups were 58.1% (95% confidence interval, 57.0%, 59.3%) versus 44.5% (43.2%, 45.8%), with the probability ratio of clinic visits between the groups being 1.46 (1.24, 1.72). The between-group differences between the baseline and 1-year surveys were -1.50 (-2.59, -0.41) mmHg for diastolic blood pressure in the hypertension category, -0.30% (-0.53%, -0.07%) for HbA1c in the diabetes category, -0.37 (-0.48, -0.27) mmol/L for LDL-cholesterol in the dyslipidemia category, and none for proteinuria. CONCLUSION: Standardized health counseling for high-risk individuals accelerated clinic visits, with larger reductions in blood pressure, HbA1c, and LDL-cholesterol levels. The nationwide use of counseling after health checkups for high-risk individuals could help in controlling risk factors and in preventing lifestyle-related diseases.

AIM: We aimed to examine sex-specific risk factors for hyperuricemia or gout in Japanese cohorts. METHODS: We followed up 3,188 men (mean age, 55.6 years) and 6,346 women (mean age, 54.1 years) without hyperuricemia, gout, or elevated liver enzymes at baseline from 1986 to 1990 for a median of 14.6 years. The participants were considered as having hyperuricemia or gout if their serum uric acid levels were ≥ 7.0 mg/dL or they were receiving treatment for hyperuricemia or gout during annual health checkups. The sex-specific multivariable hazard ratios (HRs) of hyperuricemia or gout incidence were calculated after adjustment for smoking and drinking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia using the Cox proportional-hazard model. RESULTS: During follow-up, 733 men and 355 women had hyperuricemia or gout. Among men, the multivariable HRs (95% confidence intervals) of hyperuricemia or gout were 1.23 (1.00-1.52) and 1.41 (1.13-1.75) for drinkers of ＜46 and ≥ 46 g ethanol/day, respectively, compared with non-drinkers; 1.00 (0.81-1.24) and 1.18 (0.93-1.50) for smokers of 1-19 and ≥ 20 cigarettes/day, respectively, compared with never smokers; and 1.41 (1.20-1.65) for hypertensive compared with non-hypertensive participants. The HRs for women were 1.02 (0.70-1.48), 1.66 (1.05-2.63), and 1.12 (0.88-1.42) for current drinkers, current smokers, and hypertensive participants, respectively. For both men and women, body mass index, diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with hyperuricemia or gout incidence. CONCLUSIONS: Hypertension and alcohol drinking are risk factors for hyperuricemia or gout among men and smoking among women.

AIMS: Information is limited about the influence of obstructive sleep apnea (OSA) on developing cardiovascular disease (CVD) among Asian community-dwelling populations. We examined the association between nocturnal intermittent hypoxia as a surrogate marker of OSA and the risk of CVD in a Japanese community-based cohort study. METHODS: We used baseline surveys from 2000 to 2008 to study the cohort data of 5,313 residents from three Japanese communities who were between the ages of 40 and 74 years and initially free from ischemic heart disease and stroke. We assessed the number of 3% oxygen desaturation index (ODI) as the indicator of nocturnal intermittent hypoxia. We divided individuals into two groups depending on 3% ODI (3% ODI ≥ 5 or 3% ODI ＜5). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD according to 3% ODI. Age, sex, body mass index, alcohol, and smoking were adjusted in the multivariable models. RESULTS: During 12.8 years of the median follow-up with 66,796 person-years, 185 cases with CVD (115 stroke and 70 coronary heart disease [CHD]) were recorded. The multivariable HRs (95% CIs) were 1.49 (1.09-2.03), 2.13 (1.08-4.22), and 1.93 (1.16-3.19) for the 3% ODI ≥ 5 group versus the 3% ODI ＜5 group of developing CVD, lacunar infarction, and CHD, respectively. CONCLUSIONS: Nocturnal intermittent hypoxia may increase the risk of developing lacunar infarction and CHD among community-dwelling Japanese populations. However, we could not find a significant risk of developing total stroke or stroke subtypes such as intraparenchymal hemorrhage, subarachnoid hemorrhage, and total ischemic stroke.

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.

BACKGROUND: Laughter has been reported to have various health benefits. However, data on the long-term effects of laughter interventions on diabetes are limited. This study aimed to investigate whether laughter yoga can improve glycemic control among individuals with type 2 diabetes. METHODS: In a single-center, randomized controlled trial, 42 participants with type 2 diabetes were randomly assigned to either the intervention or the control group. The intervention consisted of a 12-week laughter yoga program. Hemoglobin A1c (HbA1c), body weight, waist circumference, psychological factors, and sleep duration were evaluated at baseline and week 12. RESULTS: Intention-to-treat analysis showed that participants in the laughter yoga group experienced significant improvements in HbA1c levels (between-group difference: -0.31%; 95% CI -0.54, -0.09) and positive affect scores (between-group difference: 0.62 points; 95% CI 0.003, 1.23). Sleep duration tended to increase in the laughter yoga group with a between-group difference of 0.4 hours (95% CI -0.05, 0.86; P = 0.080). The mean attendance rate for laughter yoga program was high (92.9%). CONCLUSIONS: A 12-week laughter yoga program is feasible for individuals with type 2 diabetes and improves glycemic control. These findings suggest that having fun could be a self-care intervention. Further studies with larger numbers of participants are warranted to better evaluate the effects of laughter yoga. CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn, identifier UMIN000047164.

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.

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.

BACKGROUND: Evidence on the effects of preventive measures for noncommunicable disease is urgently needed for low-income and middle-income countries suffering from stroke epidemics along with population aging. OBJECTIVES: We sought to examine the impact of a community-based stroke prevention program on incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and medical expenditure. METHODS: Trends in the incidences of stroke and ischemic heart disease were documented in a Japanese rural community, Kyowa, from 1981 through 2015. Trends in mortality from cardiovascular disease and in medical expenditures were compared between Kyowa and its surrounding municipalities from 1981 through 2004. RESULTS: In Kyowa, the age and-sex-adjusted incidences of stroke and of ischemic heart disease decreased by half (from 4.1 to 1.9 and from 1.5 to 0.7 per year/1000 persons, respectively) over the past 35 years. A similar decreasing trend was observed for the age and-sex-adjusted mortality from cardiovascular disease, and this decreasing trend occurred earlier than that in the surrounding municipalities. The medical expenditures for cardiovascular disease became lower in Kyowa than in the surrounding municipalities over time. CONCLUSION: Our study's findings suggest that a community-based stroke prevention program augmented the decline in the incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and attenuated the increase in medical expenditures for cardiovascular disease.

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 evacuated 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. CONCLUSIONS: Excessive drinking post-disaster may be associated with an increased risk of hypertension among men and women, especially among women in the evacuation areas.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Soluble antigen by VZV skin test enhanced VZV-specific cell-mediated immunity, and it persisted for at least one 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. This article is protected by copyright. All rights reserved.

BACKGROUND: Few studies have provided observational data on long-term trends in the incidence of stroke and its subtypes, and shown the urban-rural disparities of stroke incidence in Japan. METHODS: A multiple-source, community-based stroke surveillance was performed since 1963/1964 to determine all first-ever stroke cases among Japanese residents aged ⩾40 years living in the Minami-Takayasu district in Yao city, an urban community, and Ikawa town, a rural community. Sex-specific, age-standardized incidence per 1000/year with 95% confidence intervals was calculated during seven periods of 1963/1964-1971 (urban population (% men): 3242 (47.3%); rural population (% men): 2311 (46.0%)), 1972-1979, 1980-1987, 1988-1995, 1996-2003, 2004-2011, and 2012-2018 (13,307 (46.7%); 3586 (44.8%)). RESULTS: The age-standardized incidence of all strokes in the Japanese urban community decreased from 6.60 to 1.15 per 1000/year for men and 3.28 to 0.59 for women. In the rural community, the corresponding incidence decreased from 11.51 to 1.98 for men and 6.46 to 1.31 for women. Similar reductions were observed in the incidence of intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke, and lacunar stroke. In the period of 2012-2018, the incidence ratios (95% confidence intervals) of all strokes for the rural compared to the urban community were 1.72 (1.08-2.75) for men and 2.23 (1.23-4.03) for women. CONCLUSION: The stroke incidence continued to decline in both urban and rural Japanese communities with the regional disparities over the past half century, whereas it remained higher than that in many Western countries.

OBJECTIVE: We aimed to longitudinally clarify the changes in cardiovascular disease risk factors associated with menopause in Japanese women in the 2000s. METHODS: Of the 4,596 women who underwent health examinations between 2007 and 2012 in three communities of the Circulatory Risk in Communities Study, 263 women who reported going through menopause during that period were included in the study. We randomly selected 1,665 men as control subjects who participated in a health examination at least once between 2001 and 2009 and at least once between 2010 and 2018 by 1:1 pair-matching for age, community, and examination year. The health examination data from 3 to 6 years before (2001-2009) and after menopause age (2010-2018) were compared in terms of body mass index, systolic and diastolic blood pressure levels, serum total cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin A1c, hemoglobin, aspartate aminotransferase, alanine aminotransferase, and current smoker status. RESULTS: Compared with the men, the women showed a greater increase in serum total cholesterol (+16.7 vs -3.1 mg/dL, P < 0.001), non-high-density lipoprotein cholesterol (+15.9 vs -6.3 mg/dL, P < 0.001), fasting triglycerides (+1.2 vs +1.0 mg/dL, P = 0.027), triglycerides regardless of fasting status (+1.2 vs -0.9 mg/dL, P < 0.001), uric acid (+0.5 vs +0.2 mg/dL, P = 0.008), hemoglobin (+0.9 vs -0.3 g/dL, P < 0.001), aspartate aminotransferase (+2.9 vs -2.7 IU/L, P < 0.001), and alanine aminotransferase (+2.9 vs -2.6 IU/L, P < 0.001). No differences were found in the changes in body mass index, systolic and diastolic blood pressures, and hemoglobin A1c between the women and the matched men. CONCLUSIONS: Menopause may be a crucial factor related to changes in serum total cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin, and liver enzymes.

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.

AIMS: Evidence on the risk factors for incident heart failure in Asia has been limited. We sought to identify the risk factors for pre-heart failure or symptomatic heart failure, based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), in the Japanese general population. METHODS: We performed a retrospective cohort study based on the Circulatory Risk in Communities Study involving 5335 Japanese individuals whose NT-proBNP levels were measured between 2010 and 2015. Of these, 2768 people aged between 30 and 69 years who undertook annual cardiovascular risk surveys at least once between 1990 and 2000 were retrospectively eligible to be participants in this study. We performed multivariable logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-heart failure or symptomatic heart failure defined as NT-proBNP >400 pg/mL or as having a diagnosis of heart failure and taking medication for heart failure for several cardiovascular risk factors (body mass index, blood pressure, diabetes mellitus, total cholesterol, triglyceride, smoking status, drinking status). RESULTS: We identified 85 cases of heart failure. The multivariable ORs (95% CIs) were 5.70 (2.70-12.0) for body mass index of 27-29.9 kg/m2 and 5.91 (2.19-16.0) for ≥30 kg/m2 compared with 21-22.9 kg/m2 ; 2.49(1.01-6.13) for systolic blood pressure of ≥160 mmHg vs. <130 mmHg; 2.87(1.23-6.68) for diastolic blood pressure of ≥100 mmHg vs. <80 mmHg; 5.16(2.14-12.4) for diabetes vs. non-diabetes; and 2.24 (0.92-5.49) for current smokers of ≥20 cigarettes/day vs. never smokers. The multivariable ORs (95% CIs) of the number of risk factors, defined as the sum of four risk factors (obesity, hypertension, diabetes, and current smoker) was 6.80 (3.69-12.5) for ≥2 risk factors vs. no risk factors. CONCLUSIONS: The accumulation of these risk factors was associated with a graded higher risk of pre-heart failure or symptomatic heart failure.

OBJECTIVE: To examine the association between positive psychological factors and the risk of pneumonia-associated mortality in a large prospective Japanese cohort. METHODS: The Japan Collaborative Cohort Study assessed 64,231 participants (26,293 men and 37,938 women), aged 40-79 years, without a history of stroke, myocardial infarction, cancer or tubercules at baseline (1988-1990). We used self-administered questionnaires about lifestyle, medical history, and mental states, including three positive psychological factors, and followed-up for mortality outcomes until the end of 2009. The Cox proportional hazard model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of pneumonia-associated mortality after adjustment for potential confounding factors, mutually positive psychological factors, and consideration for the competing risk. RESULTS: Having Ikigai (in Japanese) was inversely associated with the risk of pneumonia-associated mortality in both men and women; the multivariable HRs (95% CIs) for high versus low levels were 0.68 (0.48-0.97), P trend =0.090 and 0.66 (0.43-1.00), P trend =0.146, respectively. Such inverse associations were more pronounced in working men and non-working women; the multivariable HRs (95% CIs) for high versus low levels were 0.52 (0.32-0.85), P trend =0.010 and 0.59 (0.37-0.94), P trend =0.079, respectively. Being relied upon by others and Enjoyment of life was not associated with the risk in both genders. CONCLUSION: Having Ikigai was associated with a lower risk of pneumonia-associated mortality in both genders, especially in working men and non-working women.

OBJECTIVE: To examine whether bean intake (including soybeans) among Japanese adults is associated with risk of disabling dementia severe enough to require care under the national insurance system. METHODS: This cohort study involved 3739 individuals aged 40 to 64 years. The participants were categorized into five groups based on their dietary bean intake estimated by a 24h dietary recall. Hazard ratios and 95% confidence intervals of disabling dementia were estimated using Cox proportional hazard models adjusted for potential confounding factors (smoking, drinking, and intakes of energy and fish). RESULTS: During the 59,681 person-year follow-up, 670 cases of disabling dementia were observed. A weak inverse association between bean intake and risk of disabling dementia was found; the multivariable hazard ratios (95% CIs) were 0.79 (0.62-1.00), 0.80 (0.63-1.01), 0.84 (0.67-1.06), and 0.78 (0.62-0.99) for the four groups with higher bean intake, respectively, compared with the lowest group (P for trend = 0.21). A significant inverse association was observed for dementia without a history of stroke; for the four groups with higher bean intake the multivariable hazard ratios were 0.81 (0.61-1.08), 0.70 (0.52-0.95), 0.71 (0.52-0.95), and 0.69 (0.51-0.92), respectively, (P for trend = 0.03). No such association was observed for dementia with history of stroke. The group with increased natto intake were inversely associated with risk of disabling dementia (P for trend = 0.003), but tofu intake was not (P for trend = 0.19). CONCLUSIONS: Bean intake was inversely associated with risk of disabling dementia in those without a history of stroke.

There has been an increase in lifestyle-related diseases in Fukushima Prefecture since the Great East Japan Earthquake. However, the overall long-term trends of lifestyle-related diseases in the Fukushima Prefecture according to the evacuation and other area are not reported. Therefore, we examined the long-term trends in the prevalence of metabolic syndrome before and after the Great East Japan Earthquake in Fukushima Prefecture according to these areas using a national database. The target population was approximately 330,000-440,000 per year; Fukushima Prefecture residents aged 40-74 years who underwent specific health check-ups during 2008-2017 participated in the study. Fukushima was divided into mountainous, central, coastal and evacuation areas. Using the Poisson regression model, the prevalence of metabolic syndrome in each fiscal year was determined by gender and age group for each location and compared before and after the disaster as well as between areas. Prevalence increased significantly throughout the observation period, particularly in the evacuation area. Age- and gender-adjusted prevalence rates significantly increased from 16.2% in 2010 to 19.5% in 2012 (prevalence ratios = 1.21) and 20.4% in 2017 in the evacuation area. Among other areas, coastal areas showed the highest increase with 17.9% (2017), followed by central areas with 16.5% (2017) and mountainous areas with 18.3% (2016). These increases were particularly high among men and the elderly. The prevalence of metabolic syndrome increased rapidly after the disaster, especially in evacuation area, and continued for subsequent 6-7 year. Long-term monitoring and measures to prevent lifestyle-related diseases are needed after major disasters, especially in evacuation areas, among men and the elderly.

AIM: This study aimed to investigate whether the impact of body mass index (BMI) on the risk of cardiovascular disease (CVD) has changed among the 1960s, 1970s, 1980s, 1990s, and early 2000s in Japan. METHODS: The study population consisted of residents in Japan aged 40-69 years who had no history of CVD. The baseline surveys have been conducted every year since 1963. We defined the first, second, third, fourth, and fifth cohorts as 1963-1969 (n=4,248), 1970-1979 (n=6,742), 1980-1989 (n=12,789), 1990-1999 (n=12,537), and 2000-2005 (n=9,140) respectively. The participants were followed up for a median of 15 years for each cohort to determine the incidence of CVD. We classified them into four categories (BMI ＜21.0, 21.0-＜23.0, 23.0-＜25.0, and ≥ 25.0 kg/m 2). RESULTS: From 1963-1969 to 2000-2005, the prevalence of BMI ≥ 25.0 increased over time. Compared with BMI 23.0-＜25.0, the age-, sex- and community-adjusted hazard ratios (95% confidence interval [CIs]) of CVD for BMI ≥ 25.0 were 1.10 (0.77-1.57), 0.89 (0.68-1.18), 1.03 (0.85-1.26), 1.28 (1.04-1.58), and 1.36 (1.04-1.78)in the first, second, third, fourth, and fifth cohorts, respectively. The corresponding population attributable fractions were 2.0% (nonsignificant), -2.6% (nonsignificant), 0.9% (nonsignificant), 7.6%, and 10.9%. Further adjustment for systolic blood pressure and antihypertensive medication use in the fourth and fifth cohorts attenuated the associations, which may reflect that blood pressure may mediate the BMI-CVD association. CONCLUSION: The proportion of CVD attributable to overweight/obesity has increased during the periods between 1963-1969 and 2000-2005. The significant associations between overweight/obesity and risk of CVD after the 1990s were mediated by blood pressure levels.

AIMS: The evidence for the impact of alcohol consumption on long-term mortality among myocardial infarction (MI) survivors was limited. We aimed to examine whether alcohol consumption was associated with cause-specific and all-cause mortality in men with or without a history of MI. METHODS: A total of 32,004 men aged 40-79 years with no history of MI and 1,137 male MI survivors, free of stroke and cancer, were followed through the end of 2009. Alcohol consumption was assessed using self-administered questionnaires at baseline and five years. RESULTS: In MI survivors, consuming 23-45 g/day of alcohol was associated with a lower risk of coronary heart disease (CHD) mortality compared to never drinkers: the multivariable hazard ratio was 0.36 (95% confidence interval: 0.16-0.80). In non-MI men, a 10-26% lower risk was observed at ＜23 or 23-45 g/day with the U-shaped association for CHD, cardiovascular disease, other causes, and all causes (P-quadratic ＜0.001). CONCLUSION: Alcohol consumption of 23-45 g/day was associated with a lower CHD mortality in MI survivors as so in men without MI.

Early diagnosis and treatment are necessary to prevent lifestyle-related diseases among high-risk individuals. This study aimed to examine the impact of counselor characteristics on clinic visits among individuals at high risk for lifestyle-related diseases. A total of 8975 patients aged 40 to 74 years with lifestyle-related comorbidities, who underwent an annual health checkup and received health counseling, were included in this study. Data intervention timing, mode of counseling, number of counseling sessions, and explanation methods were collected. We assessed the impact of counselor characteristics, including profession (public health nurse, clinical nurse, and nutritionist), age, and years of counseling experience, on counseling outcomes. The probability ratios (95% confidence intervals) of clinic visits were 1.22 (1.11–1.35) for public health nurses and 1.04 (0.90–1.20) for nurses compared with nutritionists. After adjustment for participant and counselor characteristics and initial timing, mode, and number of counseling sessions, the corresponding probability ratios (95% confidence intervals) were 1.16 (1.05–1.29) and 1.12 (0.95–1.31), respectively. Counselor age and years of experience did not influence clinic visits of the target population. Public health nurses were more effective in increasing clinic visits among the target population owing to their profession-specific knowledge, skills, and experience.

AIMS: Epidemiological evidence is extremely limited about high-sensitivity cardiac troponin T (hs-cTnT) and future coronary heart disease (CHD) events for the general population in countries with low mortality from CHD. Therefore, we investigated the association between hs-cTnT levels and the risk of incident CHD using a nested case-control study in a large Japanese cohort study. METHODS: The participants were residents of four Japanese communities in the Circulatory Risk in Communities Study (CIRCS). We obtained 120 cases (81 men and 39 women, aged 38-86 years at baseline) of first incident CHD and 240 controls matched by age, sex, communities, and blood sampling term. Serum hs-cTnT levels were measured using an electrochemiluminescence immunoassay with stored sera collected between 2001 and 2011. The median period between sampling at survey and CHD incidence was 2.0 (interquartile range, 0.9-3.7) years. After adjusting for conventional risk factors, the multivariable odds ratios (ORs) of CHD were calculated using conditional logistic regression analyses. RESULTS: hs-cTnT ranged from ≤ 3 (assay detection limit) to 155 ng/L. Compared with the lowest quartile of hs-cTnT, multivariable ORs (95% confidence intervals) of CHD for the second, third, and highest quartiles were 1.30 (0.57-2.95), 2.48 (1.09-5.64), and 3.01 (1.27-7.12), respectively. Similar associations were observed after adjusting for estimated glomerular filtration, or after excluding matched groups, including people with chronic kidney disease. CONCLUSION: Serum hs-cTnT could predict CHD in the Japanese general population. These findings implicate a benefit from monitoring hs-cTnT to predict CHD even among populations in countries with low mortality from CHD.

BACKGROUND: This study aimed to investigate the association between evacuation status and lifestyle-related disease risks among Fukushima residents following the Great East Japan earthquake. METHODS: Fukushima health management survey respondents were classified into non-evacuees, returnees, evacuees in lifted areas, and evacuees in banned areas. During a seven-year follow-up, 22,234 men and 31,158 women were included. Those with a history of diabetes, hypertension, or dyslipidemia at baseline were excluded. The odds ratios of risk factors (ORs) and 95% confidence intervals (CIs) for diabetes, hypertension, and dyslipidemia were calculated using a logistic regression model. Spatial autocorrelation of the prevalence of these diseases in the Fukushima area in 2017, was calculated to detect the disease prevalence status. RESULTS: The risks of diabetes, hypertension, and dyslipidemia were higher in evacuees in banned areas than in non-evacuees; the multivariable ORs were 1.32 (95% CI: 1.19-1.46), 1.15 (1.06-1.25), and 1.20 (1.11-1.30) for diabetes, hypertension, and dyslipidemia, respectively. Returnees and evacuees in lifted areas had no increased risk of diseases. The area analyzed had a non-uniform spatial distribution of diabetes, hypertension, and hyperlipidemia, with clusters around Fukushima and Koriyama. CONCLUSION: Our findings imply the need for continuous support for evacuees in banned areas.

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.

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.

AIMS: We investigated the optimal cut-off points of nonfasting and fasting triglycerides in Japanese individuals with lower average triglyceride levels than westerners. METHODS: Residents aged 40-69 years without a history of ischemic heart disease or stroke were enrolled between 1980 and 1994 and followed. Serum triglyceride concentrations were measured from 10851 nonfasting (＜8 h after meal) and 4057 fasting (≥ 8 h) samples. As a prerequisite, we confirmed the shape of a receiver operating characteristic (ROC) curves, the area under ROC curves (AUC), and the integrated time-dependent AUC. We identified optimal cut-off points for incident ischemic heart disease based on C-statistic, Youden index, and Harrell's concordance statistic. We used dichotomized concentrations of triglycerides via the univariate logistic regression and Cox proportional hazards regression models. We also calculated multivariable hazard ratios and population attributable fractions to evaluate the optimal cut-off points. RESULTS: Nonfasting and fasting optimal cut-off points were 145 mg/dL and 110 mg/dL, with C-statistic of 0.594 and 0.626, Youden index of 0.187 and 0.252, and Harrell's concordance statistic of 0.590 and 0.630, respectively. The corresponding multivariable hazard ratios of ischemic heart disease were 1.43 (95%CI 1.09-1.88)and 1.69 (1.03-2.77), and the corresponding population attributable fractions were 16.1% (95%CI 3.3-27.2%) and 24.6 (-0.3-43.3). CONCLUSION: The optimal cut-off points of nonfasting and fasting triglycerides in the Japanese general population were 145 mg/dL and 110 mg/dL, respectively, lower than the current cut-off points recommended in the US and Europe.

BACKGROUND: This study aimed to investigate the association between retinal microvascular abnormalities and the risk of incident stroke and its subtypes in the general Japanese population. METHODS: A total of 12 965 residents aged 40-74 years without a history of stroke and/or coronary heart disease underwent retinal photography during the annual health checkups of four Japanese communities between 1990 and 1999. Retinal microvascular abnormalities, such as the presence or absence of generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex, and retinal hemorrhages were graded using standard protocols. RESULTS: During a median follow-up of 20 years, 817 patients were diagnosed with incident stroke. Retinal microvascular abnormalities were positively associated with the risk of total stroke; after adjustment for age, sex, community, SBP, antihypertensive medication use, and other cardiovascular risk factors, the multivariable hazard ratio [95% confidence interval (CI)] was 1.68 (1.42-1.98), 1.67 (1.34-2.07), 1.41 (1.17-1.72), 1.54 (1.26-1.87), and 1.57 (1.19-2.07) for generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex, and retinal hemorrhages, respectively. Similar positive associations were observed for the risk of stroke subtypes, except for subarachnoid hemorrhage, for which no association was observed. Furthermore, the positive associations were similar in participants with and without hypertension. CONCLUSION: Retinal microvascular abnormalities were positively associated with the risk of incident stroke in the general Japanese population. Routine retinal photography could provide positive clinical insights into stroke risk stratification independent of blood pressure, antihypertensive medication use, and other risk factors.

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.

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.

AIMS: Higher serum uric acid (UA) may impair endothelial function. However, population-based evidence examining the association between serum UA levels and endothelial function remains to be limited. Thus, in this study, we aimed to investigate this in the general population. METHODS: In this cross-sectional study, 1000 participants (496 males and 504 females), aged 30-79 years, free from a history of gout, have undergone both serum UA and brachial artery flow-mediated dilation (FMD) measurements. Participants were divided into four groups based on serum UA quartiles. Logistic regression models were used to calculate odds ratios (ORs) for low FMD according to the serum UA levels. RESULTS: In total, 203 participants (138 males and 65 females) with %FMD ≤ 5.0% were identified to have endothelial dysfunction. The multivariable OR of low FMD for highest quartiles vs. lowest quartiles was 2.39 (95% confidence interval [CI]: 1.32-4.34), while OR per 1-standard deviation (SD) increment was 1.28 (95% CI: 1.04-1.56). The positive association was noted to be more evident in females (OR per 1-SD increment: 1.46; 95% CI: 1.08-1.96) than in males and confined to individuals not using antihypertensive medications. The ORs per 1-SD increment were 1.01 (95% CI: 0.68-1.50) among individuals using antihypertensive medications and 1.43 (95% CI: 1.12-1.81) among individuals not using antihypertensive medications. CONCLUSION: Higher serum UA was positively associated with the prevalence of endothelial dysfunction in samples of the general Japanese population and that positive association was confined to individuals not using antihypertensive medications.

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.

AIM: Seaweed contains soluble dietary fibers, potassium, and flavonoids and was recently reported to be inversely associated with the risk of coronary heart disease and mortality from stroke. However, epidemiological evidence on this issue has remained scarce. METHODS: At the baseline survey of four Japanese communities between 1984 and 2000, we enrolled 6,169 men and women aged 40-79 years who had no history of cardiovascular disease. We assessed their seaweed intake using the data from a 24 h dietary recall survey and categorized the intake into four groups (0, 1-5.5, 5.5-15, and ≥ 15 g/day). We used sex-specific Cox proportional hazards models to examine the association between seaweed intake and risk of cardiovascular disease (stroke, stroke subtypes, and coronary heart disease). RESULTS: During the 130,248 person-year follow-up, 523 cases of cardiovascular disease occurred: 369 cases of stroke and 154 cases of coronary heart disease. Seaweed intake levels were inversely associated with the risk of total stroke and cerebral infarction among men but not among women. Adjustment for cardiovascular risk factors did not change the associations: the hazard ratios (95% confidence intervals; P for trend) for the highest versus lowest categories of seaweed intake were 0.63 (0.42-0.94; 0.01) for total stroke and 0.59 (0.36-0.97; 0.03) for cerebral infarction. No associations were observed between seaweed intake and risks of intraparenchymal hemorrhage, subarachnoid hemorrhage, or coronary heart disease among men or women. CONCLUSIONS: We found an inverse association between seaweed intake and risk of total stroke, especially that from cerebral infarction, among Japanese men.

BACKGROUND: The impact of body mass index on incidence of herpes zoster is unclear. This study investigated whether it 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 (95% confidence intervals) of herpes zoster incidence for overweight versus normal-weight groups were 0.67 (0.51-0.90) in all participants, and 0.57 (0.39-0.83) in women, with no significant difference for men. CONCLUSIONS: Being overweight was associated with a lower incidence of herpes zoster than being normal weight in older Japanese women.

AIM: This study aimed to investigate the associations of leukocyte count with the risks of stroke and coronary heart disease among the general Japanese population. METHODS: A total of 5,242 residents aged 40-69 years living in two Japanese communities underwent leukocyte count measurements between 1991 and 2000, and the data were updated using 5- or 10-year follow-ups or both. Participants who had histories of stroke, coronary heart disease, or high values of leukocyte count (＞130×102 cells/mm3) were excluded. Hazard ratios with 95% confidence intervals (CIs) were calculated according to quartiles of cumulative average leukocyte count. RESULTS: During follow-up of 21 years, 327 stroke and 130 coronary heart disease cases were determined. After adjustments for age, sex, community, and updated cardiovascular risk factors, the multivariable hazard ratio (95% CI) for the highest versus lowest quartile of leukocyte count was 1.50 (1.08-2.08) for ischemic stroke, 1.59 (1.00-2.51) for lacunar infarction, 1.42 (0.90-2.26) for non-lacunar infarction, 2.17 (1.33-3.55) for coronary heart disease, and 1.40 (1.11-1.76) for total cardiovascular disease. In smoking status-stratified analyses, the corresponding multivariable hazard ratio (95% CI) was 2.45 (1.11-5.38) for ischemic stroke, 2.73 (1.37-5.44) for coronary heart disease in current smokers, 2.42 (1.07-5.46), 1.55 (0.58-4.15) in former smokers, and 1.17 (0.75-1.82), 1.78 (0.83-3.82) in never smokers. CONCLUSION: Leukocyte count was positively associated with the risks of ischemic stroke and coronary heart disease among the general Japanese population, especially in current smokers.

AIM: We aimed to examine the impact of high-risk levels of cardiovascular risk factors on the incidence of cardiovascular disease (CVD) in overweight and non-overweight individuals without treatment for the risk factors. METHODS: A total of 8,051 individuals aged 40-74 years without a history of CVD and/or without treatment for hypertension, diabetes, hyperlipidemia, and kidney disease at baseline in 1995-2000 were followed up for a median of 14.1 years. We classified the participants into three risk categories (low-, intermediate-, and high-risk groups) on the basis of individual risk factors (blood pressure, serum glucose, low-density lipoprotein cholesterol [LDL-C], and urinary protein) according to the guidelines of Japanese clinical societies. The high-risk group (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, fasting serum glucose ≥ 130 mg/dL or non-fasting serum glucose ≥ 180 mg/dL, LDL-C ≥ 180 mg/dL, proteinuria ≥ 2+) needed to refer to physicians or start treatment immediately. Overweight was defined as a body mass index of ≥ 25 kg/m2. RESULTS: Compared with those in the non-overweight low-risk group, the hazard ratios (HRs) (95% confidence intervals, population-attributable fractions [PAFs]) of CVD in the high-risk categories of blood pressure were 2.0 (1.4-2.9, 7.0%) in the non-overweight high-risk group and 2.9 (1.9-4.3, 6.8%) in the overweight high-risk group. The corresponding HRs (95% confidence intervals, PAFs) of serum glucose were 2.0 (1.2-3.4, 2.5%) and 2.2 (1.1-4.3, 1.5%) in the non-overweight and overweight high-risk groups, respectively. Such associations were not observed for the high-risk group of LDL-C and proteinuria. CONCLUSIONS: The present long-term observational study implies that targeting persons with non-treated severe hypertension and diabetes is prioritized to prevent CVD regardless of overweight status.

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 SD 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. CONCLUSIONS: 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.

BACKGROUND: Despite the hypoglycemic and antioxidant effects of manganese, only one recent Chinese study has investigated the association between dietary manganese intake and type 2 diabetes. METHODS: We recruited 19,862 Japanese men and women in the Japan Collaborative Cohort Study. The participants completed a food frequency questionnaire at the baseline survey (1988 = 1990) and a diabetes history at both baseline and 5-year surveys. We calculated the odds ratios (95 % CIs) of the 5-year cumulative incidence of self-reported physician-diagnosed type 2 diabetes according to quartiles of dietary manganese intake. RESULTS: Within the 5-year period, we confirmed 530 new cases of type 2 diabetes (263 in men and 267 in women) with a 5-year cumulative incidence of 2.7 % (3.6 % in men and 2.1 % in women). Higher manganese intake was inversely associated with the women's but not the men's cumulative risk of type 2 diabetes over the 5-year period. In a full model adjusted for the participants' characteristics, diabetes risk factors and a wide range of dietary variables, the multivariable odds ratios (95 %CIs) of type 2 diabetes across the increasing quartiles of manganese intake (Q1 to Q4) were 1.00, 0.97 (0.65, 1.43), 1.04 (0.67, 1.61) and 1.10 (0.64, 1.92), p-trend = 0.66 among men and 1.00, 0.74 (0.51, 1.06), 0.62 (0.41, 0.94) and 0.53 (0.31, 0.88), p-trend = 0.01 among women. The association was observed mainly for those with low iron intake in women, particularly premenopausal women. CONCLUSION: Strong inverse associations between dietary manganese intake and risk of type 2 diabetes were observed in women but not men.

BACKGROUND: Few studies have investigated the association between serum albumin levels and the risk of stroke subtypes among the general Japanese population.Methods and Results:In this study, 5,071 men and 7,969 women aged 40-74 years, initially free from stroke, coronary artery disease, and kidney and hepatic failure, and residing in 4 Japanese communities completed a baseline risk factor survey between 1985 and 1994. During the 24-year follow-up, 528 men and 553 women experienced stroke. In the entire study cohort, multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) of total stroke, ischemic stroke, and intracerebral hemorrhage for the lowest vs. highest quartiles of serum albumin were 1.45 (1.18-1.77), 1.52 (1.17-1.97), and 1.57 (1.04-2.37), respectively. In men, multivariable HRs (95% CIs) for total stroke, ischemic stroke, and intracerebral hemorrhage in the lowest vs. highest serum albumin quartile were 1.44 (1.07-1.92), 1.48 (1.03-2.11) and 1.71 (0.92-3.18), respectively, whereas in women they were 1.50 (1.13-1.99), 1.63 (1.11-2.39), and 1.56 (0.89-2.74), respectively. Similar inverse associations were observed for each of the ischemic stroke subtypes, but not for subarachnoid hemorrhage. CONCLUSIONS: Low serum albumin levels were associated with an increased risk of total stroke, ischemic stroke, ischemic stroke subtypes, and intracerebral hemorrhage.

Background Evidence on the associations of carotid intima-media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population. Methods and Results Maximum intima-media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima-media thicknesses of the common carotid artery were 1.97 (1.26-3.06) for total stroke, 1.52 (0.67-3.41) for hemorrhagic stroke, 2.45 (1.41-4.27) for ischemic stroke, 3.60 (1.64-7.91) for lacunar infarction, 1.53 (0.69-3.41) for nonlacunar cerebral infarction, 2.68 (1.24-5.76) for coronary artery disease, and 2.11 (1.44-3.12) for cardiovascular disease (similar results were found for maximum intima-media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09-2.30) for total stroke, 1.25 (0.58-2.70) for hemorrhagic stroke, 1.74 (1.13-2.67) for ischemic stroke, 1.84 (1.03-3.19) for lacunar infarction, 1.58 (0.80-3.11) for nonlacunar cerebral infarction, 2.11 (1.20-3.70) for coronary artery disease, and 1.71 (1.25-2.35) for cardiovascular disease. Conclusions Maximum intima-media thicknesses of the common carotid artery, maximum intima-media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.

AIMS: Patients with chronic kidney disease (CKD) have a higher burden of cardiovascular morbidity and mortality than the general population. Endothelial dysfunction has been suggested to play a role in both glomerular filtration rate loss and cardiovascular damage. Thus, the present study aimed to evaluate the relationship between endothelial dysfunction and the prevalence of CKD in the general Japanese population. METHODS: We conducted a cross-sectional study of 1042 men and women aged 30-81 years in two communities under the Circulatory Risk in Communities Study between 2013 and 2017. Endothelial function was evaluated by percent change of brachial artery flow-mediated dilation (%FMD) before and after the cuff inflation. RESULTS: Among the total 1042 participants, there were 62 cases of CKD (~6%). The multivariable odds ratios (ORs) (95% confidence intervals [CIs]) of CKD according to quartiles of %FMD were 2.02 (0.68-5.99), 3.56 (1.27-9.94), and 3.14 (1.10-8.93) for the third to lowest quartile compared with the highest %FMD quartile; p for trend=0.02. The respective multivariable ORs (95% CIs) of CKD in subjects without antihypertensive medication use (39 cases among 886 subjects) were 1.83 (0.46-7.33), 3.41 (0.92-12.61), and 4.60 (1.22-17.31); p for trend=0.01, and that for one-point decrement in %FMD was 1.16 (1.00-1.35); p for interaction with the status of antihypertensive medication use was 0.12. CONCLUSIONS: Our cross-sectional study suggested the relationship between endothelial dysfunction and the higher prevalence of CKD in the general Japanese population.

BACKGROUND: The association between overweight and chronic musculoskeletal pain may vary by anatomical site and be modified by hypertension status. This study examined the associations between overweight and low back and knee pains and their effect modification by hypertension status. METHODS: We conducted a community-based cross-sectional study involving 2,845 adults (1,080 men and 1,765 women) aged 40-89 years. Chronic knee pain (CKP) and low back pain (CLBP) lasting more than 3 months were categorized into more or less severe pain. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between overweight and more or less severe CKP and CLBP were determined using logistic regression and stratified by hypertension status. Adjustment variables were age, sex, area, hypertension, smoking and drinking status, inactivity, job category, mental stress, depression, and overall CKP or CLBP. RESULTS: Overall, 288 (10.1%) and 631 (22.2%) adults had more and less severe CKP, respectively, and 284 (10.0%) and 830 (29.2%) had more and less severe CLBP, respectively. Overweight was associated with overall CKP and more or less severe CKP, regardless of hypertension status. Overweight was not associated with overall CLBP; its association was more pronounced for more severe CLBP. The association between overweight and more severe CLBP was evident among non-hypertensives (multivariable OR=1.72 [95% CI: 1.09-2.71]); however, that between overweight and less severe CLBP was not evident (multivariable OR=1.07 [0.73-1.56]). CONCLUSIONS: As hypertension may attenuate the association between overweight and CLBP, we should consider hypertension status for proper management of CLBP among overweight individuals.

This study aimed to investigate associations between Brief Job Stress Questionnaire (BJSQ)-measured job stress factors and sickness absence in Japanese workers. Among 551 healthy, employed Japanese men and women (age range: 21-73 years) who underwent mental health examinations at the Osaka Medical Center for Health Science and Promotion between 2006 and 2009, 197 (67 men, 130 women) consented to participate in this study. Their sickness absences until the end of March 2010 were then followed-up via postal mail survey, with 112 participants effectively responding to the question on sickness absence (56.9%). The hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Cox proportional hazards model, adjusting for age, sex, and lifestyle factors. Among the 112 respondents, 12 took sickness absence after their study entry, as found during the mean 2.3 years of follow-up (258.8 person-years). Among all sickness absences, those of eight participants were because of mental illness. Physical demands were positively associated with increased risks of all sickness absence (adjusted HR: 2.78, 95% CI: 1.01-7.64). Physical demands were predictive for all sickness absence, and should be alleviated at workplaces to prevent such absence.

AIM: This study aimed to investigate the association between the serum high-sensitivity C-reactive protein (hs-CRP) levels and incident atrial fibrillation risk in the general Japanese population, who have lower hs-CRP levels than the Western population, and assess whether the association is modified by sex, overweight, hypertension, and smoking status. METHODS: We conducted a prospective study in 6517 Japanese men and women aged 40-79 years without atrial fibrillation at baseline and enrolled in the Circulatory Risk in Communities Study (2002-2008). The hs-CRP levels were measured using the latex particle-enhanced immunonephelometric assay. Atrial fibrillation was identified using standard 12-lead electrocardiograms and information on physician-diagnosed atrial fibrillation history from the follow-up surveys. We used a Cox proportional hazard regression stratified by community. RESULTS: During a median follow-up of 11 years, 127 new cases of atrial fibrillation (74 and 53 cases among men and women, respectively) were found. Compared to the lowest quintile of hs-CRP levels, the multivariable hazard ratios (95% confidence intervals) were 2.54 (1.17-5.50), 2.28 (1.06-4.93), 2.92 (1.37-6.23), and 2.77 (1.30-5.91) for the second, third, fourth, and fifth (highest) quintiles, respectively. There was no significant effect modification by sex, overweight, hypertension, and smoking status (P for interaction ＞0.05). CONCLUSIONS: Elevated hs-CRP levels were significantly associated with increased risk of atrial fibrillation in the Japanese population. The association of hs-CRP levels with incident atrial fibrillation did not vary according to sex, overweight, hypertension status, or smoking status.

BACKGROUND: Reproductive history has been addressed as a risk factor for cardiovascular disease (CVD). We examined the relationship between reproductive history and CVD mortality in Japanese women. METHODS: We followed 53,836 women without previous CVD or cancer history from 1988-1990 to 2009 in a prospective cohort study. Hazard ratios (HRs) of CVD mortality were estimated according to the number of deliveries and maternal age at first delivery. RESULTS: During the follow-up, 2,982 CVD-related deaths were identified. There was U-shaped association between the number of deliveries and risk of CVD mortality with reference to three deliveries, although the excess risk of CVD mortality associated with ≥5 deliveries was of borderline statistical significance. The corresponding multivariable HRs (95% CIs) were 1.33 (1.12-1.58) and 1.11 (0.99-1.24). In addition, a higher CVD mortality was associated with maternal age ≥28 years at first delivery than maternal age of 24-27 years at first delivery. The multivariable HRs were 1.22 (1.10-1.36) for 28-31, and 1.26 (1.04-1.52) for ≥32 years at first delivery. Moreover, among women with ≥3 deliveries, maternal age ≥28 years at first delivery was associated with 1.2- to 1.5-fold increased CVD mortality. CONCLUSION: The number of deliveries showed a U-shaped association with risk of CVD mortality. Higher maternal age at first delivery was associated with an increased risk of CVD mortality, and excessive risk in women aged ≥28 years at first delivery was noted in those with ≥3 deliveries.

This study aimed to assess the association of cigarette smoking with radial augmentation index among the Asian general population. We conducted a cross-sectional population-based study including 1593 men and 2671 women aged 40-79 years. Smoking status was ascertained through interviews, and the number of pack-years was calculated. The radial augmentation index was defined as the ratio of central pulse pressure to brachial pulse pressure, as measured using an automated tonometer: the HEM-9000AI (Omron Healthcare co., Kyoto, Japan). There was a higher prevalence of an increased radial augmentation index among current male smokers who smoked ≥ 30 cigarettes/day and all female smokers than among never smokers. After adjusting for known risk factors of atherosclerosis, the multivariable odds ratio (OR) [95% confidence interval (CI)] for a high radial augmentation index for current male smokers who smoked ≥30 cigarettes/day compared with never smokers was 1.9 (1.1-3.4). The multivariable OR (95% CI) for a high radial augmentation index for former female smokers and current female smokers compared with never smokers was 1.8 (1.2-2.7) and 2.5 (1.6-3.9), respectively. Moreover, smoking pack-years was positively associated with a high radial augmentation index in both sexes. There were no relationship between smoking status and high central or brachial pulse pressures among subjects of either sex. In conclusion, cigarette smoking and cumulative smoking exposure were positively associated with an increased radial augmentation index in men who smoked heavily and in women.

BACKGROUND: Few prospective studies have explored the association between fatty acids (FA) and risk of CAD. Understanding of the role of each individual serum FA as a coronary risk or protective factor is still limited. The aim was to investigate which serum FA are associated with the incidence of CAD in Japanese subjects. Methods and Results: A prospective nested case-control study of 40-85-year-old Japanese subjects was undertaken using frozen serum samples collected from 12,840 participants who participated in cardiovascular risk surveys from 1984 to 1998 for 1 community and 1989-1997 for 2 other communities. Three control subjects per case were matched by sex, age, community, year of serum storage and fasting status. By 2005 we had identified 152 incident cases of CAD. Mean n-3-polyunsaturated and saturated FA did not differ between cases and controls, while mean n-6-polyunsaturated FA was higher in controls compared with cases. The multivariable OR of CAD for the highest vs. lowest quartiles of miristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1), and linoleic acid (18:2) were 2.8 (95% CI: 1.5-5.2), 2.7 (95% CI: 1.4-5.5), 3.2 (95% CI: 1.7-6.1) and 0.4 (95% CI: 0.2-0.7), respectively. CONCLUSIONS: High serum miristic acid, palmitic acid and palmitoleic acid have an adverse effect, and high serum linoleic acid had a protective effect, on the risk of CAD.

OBJECTIVE: To assess the association between low serum creatinine levels and an increased risk of type 2 diabetes mellitus and dysglycemia. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 3313 Japanese male workers aged 30-55 years, who underwent annual health check-ups during 2001-2008 and showed no type 2 diabetes mellitus, and underwent follow-up examinations until March 2013. Dysglycemia was defined as a fasting plasma glucose concentration of ≥110 mg/dL (6.1 mmol/L), or a non-fasting plasma glucose concentration of ≥140 mg/dL (7.8 mmol/L). A Cox proportional model was used to calculate HRs and 95% CIs for developing type 2 diabetes mellitus or dysglycemia. RESULTS: During the median 6.7-year follow-up, there were 207 cases of incident type 2 diabetes mellitus and 596 cases of incident dysglycemia, including 115 cases of type 2 diabetes mellitus among the subjects with normal glucose concentrations at baseline. After adjustment for age, body mass index and known diabetes risk factors, the multivariable HR of type 2 diabetes mellitus for the lowest category of serum creatinine (<0.7 mg/dL) vs the highest category (0.9-1.1 mg/dL) was 1.9 (95% CI 1.2 to 2.9; P for trend 0.03). The multivariable HRs of dysglycemia for the lowest category of serum creatinine versus the highest category was 1.5 (95% CI 1.1 to 1.9; P for trend 0.01). CONCLUSIONS: Low serum creatinine levels were associated with an increased risk of type 2 diabetes mellitus and dysglycemia.

OBJECTIVE: The prognostic importance of changes in ischaemic ECG abnormalities over time (especially ST-T abnormalities) among Asians has not been fully investigated. We examined the associations between changes in ischaemic abnormalities upon serial ECG (improvement, persistence, deterioration) and cardiovascular disease (CVD) risk. METHODS: A prospective study cohort was conducted with 9374 men and women aged 40-69 years in four communities. Participants had multiple ECGs at study entry and during the next 10 years, and were followed up for a median period of 23.0 years. Total CVD (stroke and coronary heart disease) was ascertained under systematic surveillance. ECG abnormalities were defined by the Minnesota Code, ST depression (Code4), abnormal T wave (Code5) and categorised into nine groups (no-no, no-minor, no-major, minor-no, minor-minor, minor-major, major-no, major-minor, major-major) by comparison with the point of entrance and maximum change. RESULTS: We documented 1196 CVD events. Compared with no-no abnormality, no-minor, minor-major and major-major in Code4, HRs (95% CI) adjusted for cardiovascular risk factors were 1.19 (1.00-1.42), 1.57 (1.15-2.12) and 1.87 (1.42-2.47). Similar results were observed in Code5. CONCLUSIONS: Changes in ischaemic ECG abnormalities from none to minor, and minor to major, as well as persistent major abnormalities, were associated with an increased risk of CVD.

This study aimed to investigate the effects of occupational status and job stress factors on cardiovascular stress reactivity in Japanese workers. In this baseline assessment between 2001 and 2009 in Osaka, Japan, we examined 928 healthy Japanese employees (330 men, 598 women) from two occupational statuses: managers/professionals and general workers. A brief job stress questionnaire was used to evaluate job stress levels. Systolic and diastolic blood pressure (SBP, DBP), heart rate, heart rate variability (high-frequency [HF], low-frequency [LF], LF/HF], and peripheral blood flow were measured at rest and during two stressful tasks. Changes in stress reactivity were calculated as the difference between the measured variables during the tasks and the rest period. Men showed inverse associations between quantitative job overload and DBP, heart rate, and LF/HF, between physical demands and blood pressure (SBP, DBP), and between a poor physical environment and HF. Men also had positive associations between qualitative job overload and heart rate, and between physical demands and peripheral blood flow (all p < 0.05). Women showed inverse associations between qualitative job overload and SBP, and showed positive associations between qualitative job overload and peripheral blood flow, and between a poor physical environment and SBP (all p < 0.05). When stratified by occupational status, significant associations between job stress and changes in stress reactivity were observed in male managers/professionals and female general workers (p < 0.05). Job stress levels are associated with changes in cardiovascular stress reactivity in men and women. Occupational status may modify these associations.

Background The US Centers for Disease Control and Prevention ensured adequate performance of the routine triglycerides methods used in Japan by a chromotropic acid reference measurement procedure used by the Centers for Disease Control and Prevention lipid standardization programme as a reference point. We examined standardized data to clarify the performance of routine triglycerides methods. Methods The two routine triglycerides methods were the fluorometric method of Kessler and Lederer and the enzymatic method. The methods were standardized using 495 Centers for Disease Control and Prevention reference pools with 98 different concentrations ranging between 0.37 and 5.15 mmol/L in 141 survey runs. The triglycerides criteria for laboratories which perform triglycerides analyses are used: accuracy, as bias ≤5% from the Centers for Disease Control and Prevention reference value and precision, as measured by CV, ≤5%. Results The correlation of the bias of both methods to the Centers for Disease Control and Prevention reference method was: y (%bias) = 0.516 × (Centers for Disease Control and Prevention reference value) -1.292 ( n = 495, R2 = 0.018). Triglycerides bias at medical decision points of 1.13, 1.69 and 2.26 mmol/L was -0.71%, -0.42% and -0.13%, respectively. For the combined precision, the equation y (CV) = -0.398 × (triglycerides value) + 1.797 ( n = 495, R2 = 0.081) was used. Precision was 1.35%, 1.12% and 0.90%, respectively. It was shown that triglycerides measurements at Osaka were stable for 36 years. Conclusions The epidemiologic laboratory in Japan met acceptable accuracy goals for 88.7% of all samples, and met acceptable precision goals for 97.8% of all samples measured through the Centers for Disease Control and Prevention lipid standardization programme and demonstrated stable results for an extended period of time.

BACKGROUND: The aim of this study was to examine whether the burden of diabetes on cardiovascular disease (CVD) in Japan has increased in recent years.Methods and Results:Three cohorts were established, consisting of Japanese residents aged 40-69 years, in 1992-1995 (n=8,744), 1996-1999 (n=7,996), and 2000-2003 (n=7,273). All participants had follow-up for a median of 10 years. Diabetes was defined according to the following criteria: (1) fasting serum glucose ≥7.0 mmol/L; (2) non-fasting serum glucose ≥11.1 mmol/L; or (3) anti-diabetic treatment at baseline. During follow-up, the number of CVD incidents was 277 in the first, 214 in the second, and 190 in the third cohorts. The prevalence of diabetes increased slightly over time. Adjusting for traditional cardiovascular risk factors, multivariable HR (95% CI) for diabetes as a cardiovascular risk factor were 1.40 (0.91-2.14) in the first, 1.93 (1.25-3.00) in the second, and 2.59 (1.77-3.81) in the third cohorts. The population attributable fraction of CVD due to diabetes was 2.8%, 5.6%, and 12.4%, respectively. CONCLUSIONS: This is the first study in middle-aged Japanese people to clarify an increased burden of CVD due to diabetes since the early 1990 s. Further efforts are needed to prevent and control diabetes through lifestyle modification and treatment. (Circ J 2016; 80: 2343-2348).

AIM: It is important to explore predictive markers other than conventional cardiovascular risk factors for early detection and treatment of chronic kidney disease (CKD), a major risk factor for end-stage renal failure. We hypothesized that serum albumin and high-sensitivity C-reactive protein (hs-CRP) to be independent markers, and examined their associations with the risk of CKD. METHODS: We examined the associations of serum albumin and hs-CRP levels with the risk of incident CKD, in 2535 Japanese adults aged 40-69 years without CKD at baseline during a median 9.0-year follow-up after adjustment for known cardiovascular risk factors. RESULTS: During the follow-up period, 367 cases of CKD developed. In multivariable analyses adjusted for known risk factors, the CKD hazard ratios (95% confidence intervals) for the highest versus lowest quartiles of serum albumin levels were 0.69 (0.40-1.17) for men and 0.42 (0.28-0.64) for women. Corresponding values for hs-CRP were 0.95 (0.54-1.67) for men and 1.85 (1.25-2.75) for women. The association of combined serum albumin and hs-CRP with the risk of CKD was examined for women. The hazard ratio was 1.72 (1.17-2.54) for low versus higher albumin levels at lower hs-CRP levels, but such an association was not observed at high hs-CRP level. The hazard ratio was 1.96 (1.44-2.66) for high versus lower hs-CRP levels at higher serum albumin levels, but such association was not observed at low serum albumin level. CONCLUSION: Both low serum albumin and high hs-CRP levels were predictive of CKD for women.

AIM: Previous studies have reported that moderate alcohol consumption is protective against cardiovascular disease, but heavy alcohol consumption increases its risk. Endothelial dysfunction is hypothesized to contribute to the development of atherosclerosis and cardiovascular disease. However, few population-based studies have examined a potential effect of alcohol consumption on endothelial function. METHODS: This study included 404 men aged 30-79 years who were recruited from residents in 2 communities under the Circulatory Risk in Communities Study in 2013 and 2014. We asked the individuals about the frequency and volume of alcohol beverages and converted the data into grams of ethanol per day. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD) measurements during reactive hyperemia. We performed cross-sectional analysis of alcohol consumption and %FMD by logistic regression analysis, adjusting for age, baseline brachial artery diameter, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, HbA1c, smoking, antihypertensive medication use, and community. RESULTS: Individuals who drank ≥ 46 g/day ethanol had a lower age-adjusted mean %FMD than non-drinkers (p＜0.01). Compared with non-drinkers, the age-adjusted odds ratios (ORs) (95% confidence interval) of low %FMD (＜5.3%) for former, light (＜23.0 g/day ethanol), moderate (23.0-45.9 g/day ethanol), and heavy (≥ 46.0 g/day ethanol) drinkers were 1.61 (0.67-3.89), 0.84 (0.43-1.66), 1.09 (0.52-2.25), and 2.99 (1.56-5.70), respectively. The corresponding multivariable-adjusted ORs were 1.76 (0.69-4.50), 0.86 (0.42-1.76), 0.98 (0.45-2.12), and 2.39 (1.15-4.95), respectively. CONCLUSIONS: Heavy alcohol consumption may be an independent risk factor of endothelial dysfunction in Japanese men.

AIMS: Retinal hemorrhage is an important finding on fundus photography. Diabetes mellitus is a cause of retinal hemorrhage, although other causes exist. We sought to better characterize the association between retinal hemorrhage and HbA1c in the Japanese population. METHODS: We conducted a prospective study of 11,644 Japanese men and women aged 30-78years between 2001 and 2011. Fundus photography was performed as part of an annual cardiovascular disease risk survey. HbA1c was determined by the latex coagulation method throughout the study. We used logistic regression models to examine the association between HbA1c and the risk of retinal hemorrhage and diabetic retinal hemorrhage. RESULTS: During a median follow-up period of 4.6years, 509 retinal hemorrhages, including 96 diabetic retinal hemorrhages, were diagnosed. HbA1c was positively associated with the risk of retinal hemorrhage and diabetic retinal hemorrhage among subjects not taking medication for diabetes mellitus at baseline, but not among subjects who were taking medication at baseline. CONCLUSIONS: HbA1c was positively associated with the risk of retinal hemorrhage and the subcategory of diabetic retinal hemorrhage among subjects not taking medication for diabetes mellitus at baseline. The association was evident for diabetic retinal hemorrhage, compared with retinal hemorrhage.

Cardiovascular stress reactivity is a predictor of atherosclerosis and cardiac events. Dehydroepiandrosterone (DHEA) protects against cardiovascular diseases, but results among previous studies have been inconsistent. We investigated the association between dehydroepiandrosterone-sulfate (DHEA-s) and cardiovascular stress reactivity in Japanese women and men. Among 979 healthy Japanese subjects (641 women and 338 men), serum levels of DHEA-s, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, heart rate variability, and peripheral blood flow were measured under rest and two types of task. Mean differences in measured variables during tasks and a post-task period were calculated as changes in stress reactivity. Variables of stress reactivity were adjusted for multiple potential confounding factors. In women, DHEA-s levels showed positive associations with changes in SBP and DBP (standardized beta=0.12, p=0.020; 0.17, 0.002, respectively). Stratification by menopausal status and other lifestyle factors (e.g., smoking status, alcohol consumption) were conducted. Significant positive associations remained in pre-menopausal (standardized beta=0.13, p=0.037; 0.18, 0.005), non-smoking (0.12, 0.010; 0.18, <0.001), and non-drinking women (0.14, 0.021; 0.21, 0.001), and women without a medical history (0.15, 0.020; 0.20, 0.001). In men, there was no significant association between DHEA-s levels and changes in stress reactivity. DHEA-s levels were positively associated with high blood-pressure reactivity to stress in women, and being menopausal, smoking, and alcohol consumption modified this association.

Individuals with an inactive acetaldehyde dehydrogenase 2 have an. elevated level of serum acetaldehyde after drinking alcohol, and this may cause an alcohol flushing response with symptoms such as facial flushing, tachycardia, headache, and nausea. Recent studies have suggested that the flushing response influences the association between alcohol consumption and various health-related outcomes. In the present study, we investigated the impact of the flushing response on the relationship between alcohol consumption and serum y -GTP levels in Japanese drinkers. We conducted a cross-sectional study of 521 Japanese drinkers (260 men and 261 'vomen) to examine the impact of the alcohol flushing response on the relationship between alcohol consumption and serum y -GTP levels. The subjects were divided into three groups according to the amount .of daily alcohol consumption. (low, <20 g; moderate, 20-39 g;. and high, >40 g). Multiple adjustments were performed with linear regression models to examine the association between daily alcohol consumption and serum y-GTP levels, adjusting for potential con- founders including the flushing response. We found that the proportion of flushers was significantly lower in the high alcohol consumption group than in the low consumption group. The results of a multivariable analysis showed that,serum y -GTP levels were significantly higher in the moderate and high consumption groups than in the low consumption group after. adjusting for all potential confounders other than the flushing response. In addition, the association between serum y -GTP levels and alcohol consumption was unchanged after adjusting for the presence of the flushing response. In conclusion, serum y -GTP levels increased with increasing alcohol-consumption regardless of the flushing response. Screening for heavy drinkers using serum y-GTP levels was very important to prevent alcohol-related diseases or health problems in health examination.

OBJECTIVES: Working is a common cause of chronic pain for workers. However, most of them need to continue working despite the pain in order to make a living unless they get a sick leave or retirement. We hypothesised that the therapeutic effect of vocational rehabilitation may depend on psychosocial factors related to the workplace. To test this hypothesis, we examined the association of work-related psychosocial factors with the prevalence of chronic pain or health-related quality of life (HRQoL) among workers with chronic pain. METHODS: We examined 1764 workers aged 20-59 years in the pain-associated cross-sectional epidemiological survey in Japan. The outcomes were (1) chronic pain prevalence among all workers and (2) low Euro QoL (EQ-5D <0.76; mean value of the current study) prevalence among workers with chronic pain according to the degree of workplace social support and job satisfaction. Workplace social support and job satisfaction were measured using the Brief Job Stress Questionnaire. Multivariable-adjusted ORs were calculated using a logistic regression model including age, sex, smoking, exercise, sleep time, work hours, body mass index, personal consumption expenditure, intensity of pain and the presence of severe depressive symptoms. RESULTS: Chronic pain prevalence was higher among males reporting job dissatisfaction compared with those reporting job satisfaction. No difference was observed among women. Chronic pain prevalence did not differ between workers of either sex reporting poor workplace social support compared with those reporting sufficient support. Among workers with chronic pain, low HRQoL was more frequent in those reporting job dissatisfaction. Similarly, low HRQoL was more frequent in patients with chronic pain reporting poor social support from supervisors or co-workers compared with patients reporting sufficient support. CONCLUSIONS: Work-related psychosocial factors are critical for HRQoL in patients with chronic pain.

BACKGROUND: Accurate measurement of total cholesterol (TC) is important for cardiovascular disease risk management. The US Centers for Disease Control and Prevention (CDC) and Cholesterol Reference Method Laboratory Network (CRMLN) perform Abell-Levy-Brodie-Kendall (AK) reference measurement procedure (RMP) for TC as a secondary reference method, and implement Certification Protocol for Manufacturers. Japanese CRMLN laboratory at Osaka performed the AK RMP for 22 years, and conducted TC certification for reagent/calibrator/instrument systems of six Japanese manufacturers every 2 years for 16 years. Osaka TC performance was examined and compared to CDC's reference values. METHODS: AK RMP involved sample hydrolysis, cholesterol extraction, and determination of cholesterol levels by spectrophotometry. The Certification Protocol for Manufacturers includes comparison with AK RMP using at least 40 fresh specimens. Demonstration of average bias ≤3% and total coefficient of variation ≤3% qualified an analytical system for certification. RESULTS: In the AK RMP used in the Osaka CRMLN laboratory, the regression equation for measuring TC was y (Osaka)=1.000x (CDC)+0.032 (n=619, R(2)=1.000). Six Japanese manufacturers had allowable performance for certification. CONCLUSIONS: The AK RMP for TC measurement was accurate, precise, and stable for 22 years. Six Japanese manufacturers were certified for 16 years.

BACKGROUND: Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. METHODS: We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. RESULTS: Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men. CONCLUSIONS: HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

BACKGROUND: The population of Japan has achieved the longest life expectancy in the world. To further improve population health, consistent and comparative evidence on mortality attributable to preventable risk factors is necessary for setting priorities for health policies and programs. Although several past studies have quantified the impact of individual risk factors in Japan, to our knowledge no study has assessed and compared the effects of multiple modifiable risk factors for non-communicable diseases and injuries using a standard framework. We estimated the effects of 16 risk factors on cause-specific deaths and life expectancy in Japan. METHODS AND FINDINGS: We obtained data on risk factor exposures from the National Health and Nutrition Survey and epidemiological studies, data on the number of cause-specific deaths from vital records adjusted for ill-defined codes, and data on relative risks from epidemiological studies and meta-analyses. We applied a comparative risk assessment framework to estimate effects of excess risks on deaths and life expectancy at age 40 y. In 2007, tobacco smoking and high blood pressure accounted for 129,000 deaths (95% CI: 115,000-154,000) and 104,000 deaths (95% CI: 86,000-119,000), respectively, followed by physical inactivity (52,000 deaths, 95% CI: 47,000-58,000), high blood glucose (34,000 deaths, 95% CI: 26,000-43,000), high dietary salt intake (34,000 deaths, 95% CI: 27,000-39,000), and alcohol use (31,000 deaths, 95% CI: 28,000-35,000). In recent decades, cancer mortality attributable to tobacco smoking has increased in the elderly, while stroke mortality attributable to high blood pressure has declined. Life expectancy at age 40 y in 2007 would have been extended by 1.4 y for both sexes (men, 95% CI: 1.3-1.6; women, 95% CI: 1.2-1.7) if exposures to multiple cardiovascular risk factors had been reduced to their optimal levels as determined by a theoretical-minimum-risk exposure distribution. CONCLUSIONS: Tobacco smoking and high blood pressure are the two major risk factors for adult mortality from non-communicable diseases and injuries in Japan. There is a large potential population health gain if multiple risk factors are jointly controlled.

目的 本研究は自覚的ストレス，うつ症状等の心理的健康と食事，運動，睡眠，飲酒，喫煙等の生活習慣との関連を検討することを目的とした。
方法 2001～02年に大阪府立健康科学センターの健康度測定コースを受診した男女7,947人（平均年齢52.4歳）を対象に，食事，運動，睡眠，飲酒，喫煙等の生活習慣を調査し，自覚的ストレスおよびうつ症状との関連について男女別に検討した。
結果 うつ症状を訴える者の頻度は自覚的ストレスを強く感じる者ほど高かった。多重ロジスティック分析の結果，男女ともに自覚的ストレス，うつ症状との関連がみられたものは，「身体活動量がかなり少ない」，「運動習慣がない」，「睡眠時間が少ない」，「朝食を抜くことがよくある」，「夕食後 1～2 時間以内に床につく」ことであった。また，男性では「間食または夜食をほぼ毎日とる」，「お腹いっぱい食べる」ことが，自覚的ストレスの多変量調整オッズ比の上昇と，「運動習慣がある」，「野菜類を毎食食べる」ことがうつ症状オッズ比の低下と関連した。女性では，「漬け物やおかずにしょうゆやソースをかけることが多い」ことが自覚的ストレスのオッズ比の上昇と，「大豆製品を毎日食べる」ことがオッズ比の低下と関連し，「煮物の味付けが濃い」ことがうつ症状のオッズ比の上昇と関連した。
結論 身体活動量が少ない，睡眠時間が少ない，朝食を抜く等の生活習慣は，男女ともに自覚的ストレス，うつ症状と関連することが示唆された。

PURPOSE: To provide the strategies, achievement and evaluation of a community health education program for salt reduction with media campaigns. METHODS: The intervention community was Kyowa town (A district of Chikusei city, census population in 1985 = 16,792) where we have systematically conducted a community-based blood pressure control program since 1981, and health education on reduction of salt intake since 1983 for primary prevention of hypertension. The education program was performed through media campaigns including use of banners, signboards, posters, and calendars with health catchphrases. We also used catchphrase-labeled envelopes when sending documents from the municipal health center to individuals. Health festivals were held annually to enhance health consciousnesses and to improve health behavior. Some of the posters and calligraphy were painted or drawn by elementary schoolchildren as part of their education. The program was evaluated by repeated questionnaires and examination of salt concentrations of miso soup and dietary salt intake. RESULTS: Between 1983 and 1988, the prevalence of persons who were aware that health consultation including blood pressure measurements were available at the town office increased from 65% to 84%. The prevalence of those who knew the salt intake goal (10 g or less/day) increased from 47% to 63% and that of those who reported to reduce salt intake also increased from 38% to 58%. As for salt concentrations of miso soup, the proportion with less than 1.1% increased from 47% to 66% between 1985 and 2004. Age-adjusted mean salt intake for persons aged 40-69 years declined from 14 g to 11 g in men and from 12 g to 10 g in women between 1982-1986 and 2000-2004. CONCLUSION: A long-term systemic education program through media campaigns proved feasible with the cooperation of community leaders, schools and food associations.

秋田県井川町の対策開始当初から最近までの脳卒中発生者の発生時症状と1年後の予後を検討し,脳卒中の重症度の推移について調べた.脳卒中対策を長期間,一貫して実施したことで,脳卒中発生率や発生数の減少に加え,発症の軽症化,予後の改善が認められた.また,高齢人口の増加にも拘わらず,脳卒中による寝たきり数の増加が近年は頭打ちになっていることが示された

1982年に実施した食品摂取頻度に関する調査に回答した住民のうち,循環器疾患の既往歴のない3517名を対象に,同一の質問紙調査を96年に実施してその変化を検討した.その結果,男女とも「肉類」「油脂」など洋食系食品群の摂取頻度は減少,「魚」「煮物」など和食系は増加し,この傾向は初回調査時の年齢区分が若い者ほど強かった.また塩分摂取と関連する食品群のうち「漬物」「みそ汁・すまし汁・スープ」は増加傾向を示したが,「梅干・塩こんぶ・つくだ煮」「ハム・ソーセージ・ちくわ・かまぼこ」は減少傾向であった.そして全ての性・年齢区分で「牛乳」「間食・果物」「コーヒー・紅茶・コーラ・ジュース・サイダー」など,補食系の食品群の摂取頻度は増加する傾向を示した

<p>To investigate associations of alcohol intake to constitutional and biochemical variables, cross-sectional studies of men aged 40-59 years from six geographical and occupational populations with varied lifestyles were conducted in the 1990's. Systolic and diastolic blood pressures, glutamic oxaloacetic transaminase, gamma glutamyl transpeptidase, HDL-cholesterol, and uric acid were linearly associated with alcohol intake in all six populations. Drinkers of 2+ drinks (46 g ethanol or more) per day showed higher levels of triglyceride, glutamic pyruvic transaminase than never-drinkers. In two urban occupational populations, men who mainly drank beer had higher uric acid levels; men mainly drinking sake had higher blood pressures and lower serum total cholesterol; men mainly drinking whiskey had higher obesity indices. These differences in constitutional and biochemical variables related to type of alcoholic beverage consumed may be due to differences in lifestyles such as diet and physical activity.</p>

We presented trends of cardiovascular risk factors and diseases in a rural population, northeastern Japan between the 1960s and the 1990s. Population blood pressure levels declined substantially with improved medical treatment for hypertension and reduction of mean dietary sodium intake from 20g/day to 14g/day. Serum total cholesterol increased from 152mg/dl to 185mg/dI for men, and 163mg/dI to 195mg/dI for women with an increased intake of meat, egg, milk and dairy products. Age-adjusted incidence rate of stroke declined 75% while that of coronary heart disease was low and stable. The prevalence of stroke and the number of stroke patients also declined in spite of an increase of the elderly. Furthermore, the number of severely- disabled stroke patients, so called bed-ridden patients decreased a half. The substantial decline in stroke incidence, prevalence along with the decline of blood pressure levels suggest an effect of population hypertension control program conducted since 1963. In nationwide, however, an increase in the prevalence of stroke patients and the number of severely disabled patients among the elderly were reported. Primary prevention of stroke through control and prevention of hypertension should be further augmented nationwide to reduce a public health burden from the disabled stroke patients in the elderly. J Epidemiol, 1996 ; 6 : S183-S188.

脳卒中は我が国の死因の第4位であることに加え、要介護の重要な危険因子である。脳卒中発症には飲酒、喫煙、身体活動、睡眠、食生活等の生活習慣、高血圧、糖尿病、心房細動等の生活習慣病及び心理社会的因子の影響が考えられるが、これら危険因子の寄与危険度の変遷を包括的かつ縦断的に地域住民を対象として評価を行った研究は欧米を含めて殆どない。そこで本研究では、長期間疫学研究を実施している地域を対象として、1980年代から2010年代まで10年毎の4つのコホートを分析することにより、我が国の脳卒中発症と予後の動向、脳卒中に関連する身体・心理・社会的因子の時代変遷を検討すること、及び脳卒中発症に関する身体心理社会的な新規の危険因子を同定し、今後の脳卒中予防対策に寄与する知見を得ることを目的とした。 秋田、茨城、大阪の30歳以上の地域住民を対象として循環器健診のデータをⅠ期：1981年～1985年、Ⅱ期：1991年～1995年、Ⅲ期：2001～2005年、Ⅳ期：2011～2015年の時期（対象人数はいずれも約10,000人）に分け、それぞれの時期の非脳卒中者を対象として、フォローアップ時期のそれぞれの時期の病型別脳卒中発症率を比較し、脳卒中の病型別の発症率の推移を比較するために、本年度はこれまで測定したデータを統合し、解析のためのデータセットを作成した。また、脳卒中発症に関連する新規の身体心理的因子に関する前向き研究を行った。 その結果、高尿酸血症は女性において全脳卒中、特に虚血性脳卒中の発症リスクを高めることが明らかになった。また、心不全のバイオマーカーであるNTproBNPは脳梗塞の発症リスクを高めることが明らかになった。さらに、心理的因子である怒りの程度はその後の循環器疾患、特に脳梗塞の発症リスクを高めることが明らかになった。

社会心理的ストレスと多くの生活習慣病との関連が報告されているが、近年、脂肪・糖代謝との関連、及び腸内細菌叢との関連が注目されるようになり、社会心理ストレスは内分泌・代謝系、腸内環境系の双方に関連している可能性がある。そこで本研究は、社会心理的ストレスと脂肪・糖代謝異常との関連に腸内細菌叢の不均衡が介在するという仮説のもとに、脳ー腸ー脂肪・糖代謝の相互連関の可能性を検証することを目的とした。地域住民を対象に社会心理的ストレス、腸内細菌叢、及び脂肪・糖代謝との関連を横断的に分析するとともに、追跡調査によって、長期に渡る社会心理的ストレス及び脂肪・糖代謝の変化が腸内細菌叢に及ぼす影響、及び腸内細菌叢が心理的ストレス、脂肪・糖代謝に及ぼす影響を明らかにする。これにより社会心理的ストレス、腸内細菌叢、及び脂肪・糖代謝との相互連関に学術的に貢献できることに加え、我が国の生活習慣病、精神的疾患の予防対策の新たな方策に貢献できる可能性がある。 本年度は福島県において健康教室に参加した人、及び秋田県において健診に参加した人において腸内細菌叢検査を実施したそれぞれ40人と140人を対象として、腸内細菌叢と健診及び生活習慣との関連を検討した。ビフィズス菌存在割合、多様度指数(シャノン・ウィナーの多様度指数)については3分位、乳酸菌についてはその検出の有無で2 群に分けてそれぞれの因子との関連を検討した結果、高血圧者では非高血圧者と比較して乳酸菌が検出限界以下の者の割合が多かった。また、宴会によく行く者ではビフィズス菌・乳酸菌・腸内細菌多様度が低位の群の割合が多く、喫煙者や身体活動が少ない者では乳酸菌が検出限界以下の割合が少なく、固形ヨーグルトを多く摂取する者ではビフィズス菌高位群の割合が多かった。

公衆衛生上の重要課題の一つで2型糖尿病の予防にとって、通常の血糖値やHbA1cでは捉えきれない血糖値スパイクや食後高血糖等の血糖変動を記録できる持続血糖測定（Continuous Glucose Monitoring: CGM）法は新たな知見が得られる可能性がある重要な方法であるが、１日数回の指尖穿刺採血による自己血糖測定による補正が必要など、一般地域集団を対象とした疫学研究への導入は困難であった。しかしながら、補正不要で装着も簡便なFGM（Flash Glucose Monitoring）装置は、地域での疫学研究を可能とした。本研究では、地域集団を対象としたコホート研究により、FGMによる個人内血糖変動の諸指標と糖尿病発症との関連を定量的に分析し、明らかにすることを目的とする。 2018年度は、循環器疫学地域コホート（CIRCS: Circulatory Risk in Communities Study）における茨城農村地域（筑西市協和地区）在住の40～59歳男女および大阪近郊（八尾市南高安地区）在住の40～64歳男女を対象として、特定健診に合わせて検査を実施した。対象者1人1人に対して文書と口頭による説明と同意取得を行ったところ、同意率は、前者で50.0%、後者で45.1%であり、FGM検査実施者は、前者が150人(男41人、女109人)、後者が171人(男38人、女133人)であった。また、FGM検査が2週間フルで記録出来た者は、前者で114人(76%)、後者で119人(70%)であり、一方、記録日数が1週間未満だった者は、前者で15人(10%)、後者で22人(13%)であった。FGM検査実施者には食行動並びに主に糖質と食物繊維に関する食物摂取頻度調査および身体活動量の調査を実施した。現在、FGM検査データおよび食物摂取頻度調査・身体活動調査データのデータセットを構築中である。

社会心理的ストレスは多くの生活習慣病と関連することが報告されているが、近年、腸内細菌叢と社会心理的ストレスとの関連が注目されるようになってきた。本研究は、社会心理的ストレスは腸内細菌叢の不均衡の原因になること、及び腸内細菌叢の不均衡を有することがうつ症状・社会不適応等の誘因になるという相互連関の可能性を検証するために、社会心理的ストレスと腸内細菌叢との関連を横断的に分析するとともに、健診データの追跡調査によって、長期に渡る社会心理的ストレスの変化が腸内細菌叢に及ぼす影響を明らかにする。さらに、これまで申請者らが行ってきたポジティブな感情を増やすための心理的介入の腸内細菌叢の不均衡の改善効果、及び腸内細菌叢の不均衡を改善するためのプレバイオティクス・プロバイオティクスによる食事介入の心理的ストレス・うつ症状の改善効果を無作為化介入試験によって明らかにすることを目的とした。本研究により社会心理的ストレスと腸内細菌叢との関連に学術的に貢献できることに加え、我が国の生活習慣病、精神的疾患の予防対策の新たな方策に貢献できる可能性がある。 今年度は、肥満を有する地域住民44名を、年齢・BMIで層別化し、無作為に、介入群（22名）と対照群（22名）に割りあて、介入群には、2週間に1回、8週間に渡って、腸内環境の改善に有効であると報告されている栄養素やそれを豊富に含む食品などに関する集団講義と個別カウンセリングで構成されるプログラムに参加もらった結果、介入群において腸内細菌の多様性が向上し、体重・腹囲が有意に減少し、抑うつのスコアの改善し、笑いの頻度が増えた。 この結果は、腸内環境に着目した栄養教育が、腸内細菌叢に影響することにより、体重・腹囲が減少し、心理的健康度が改善することを示唆したものと考えられる。

冠動脈疾患(CHD)新規発症者117人と対照234人におけるコホート内症例対照研究の結果、血清トランス脂肪酸(TFA)構成割合の第1五分位群(<0.046%)に対するCHD発症のオッズ比は、第2五分位群から順に、1.24 (0.59-2.61)、1.68(0.79-3.55)、1.44(0.67-3.11)、2.03(0.95- 4.35)であったが、多変量調整後、その階段状の関連は消失した。循環器ドック受診者870人における横断研究の結果、血清TFA構成割合と冠動脈石灰化スコアおよび頸動脈の内膜・中膜複合体厚との間に有意な関連は認められなかった。

秋田県の地域住民を対象として、要介護認定情報に基づき判定された認知症発症者に特徴的な眼底所見が存在するかについて、コホート内症例対照研究の手法にて検討しました。その結果、眼底の細動脈狭細及び網膜血管異常の累積は、将来の要介護認知症の発症リスク上昇と関連することが明らかとなりました。また、眼底の細静脈径の拡大は脳卒中発症後の認知症も含めて要介護認知症発症の予測指標となる可能性が示されました。

茨城県某市の住民を対象として、健診時に心・腎・眼連関に関わるバイオマーカーに関する疫学調査を約1万人に実施し、血清N末端プロ脳性ナトリウム利尿ペプチド(NT-proBNP)と、心電図異常、腎機能低下、眼底異常との関連を見いだした。これにより、１万人規模の総合的な大規模コホート研究のベースラインが構築され、血清NT-proBNP検査、心電図検査、血清クレアチニン検査、眼底検査を含む健診所見をベースラインとするコホート研究の基盤が完成した。

本研究では、地域住民を対象として、社会心理的ストレスと肥満、糖・脂質代謝異常との相互連関を検討することを目的とした。 秋田県及び大阪府地域住民のうち、2007年及び2008年の健診を受診し、ストレス関連の質問票の回答を得た4755人（男性1782人、女性2973人、平均年齢59歳）を対象として2014年末まで追跡調査を行った（平均追跡期間5.4年）。2014年までに1回以上健診を受診した3715人（男性1365人、女性2350人）を解析対象とした（追跡率77.7％）。 横断・縦断研究の結果、うつ症状はメタボリックシンドローム及び構成因子のうち、特に糖尿病との関連が強い可能性が示唆された。

冠動脈疾患新規発症者120人と対照240人におけるコホート内症例対照研究の結果、高感度心臓トロポニンT(hs-cTnT)第1四分位群(≦0.004ng/mL)に対する冠動脈疾患発症の多変量調整オッズ比は、第3四分位群2.50(1.08-5.77)、第4四分位群2.61 (1.10-6.20)と有意な関連が認められた。また、循環器ドック受診者870人を対象とした横断研究の結果、hs-cTnT≦0.003ng/mL群に対する冠動脈石灰化有所見の多変量調整オッズ比は0.004-0.005ng/mL群で2.12(1.08-4.35)、0.006ng/mL以上群で1.54(0.72-3.28)であった。

秋田、茨城、大阪の3地域において、1985年以降の脳出血の発症登録を行うとともに、1985～94年に健診を受診した40-69歳男女9,086人の脳卒中の危険因子について部位別に前向きに検討した。 1985年から2010年にかけて、深部脳内出血は減少傾向であったが、大脳皮質下・小脳出血は横ばいだった。収縮期血圧高値、肥満、心電図ST-T異常、多量飲酒（2合以上/日）はそれぞれ深部脳内出血発症のリスクの上昇と関連していた。一方、血清総コレステロール低値は脳内出血発症の危険度が高く、特にその関連は大脳皮質下・小脳出血において強くみられた。糖尿病、喫煙と脳内出血の発症との有意な関連はみられなかった。

本研究では、地域住民を対象に、食行動・身体活動・社会心理要因とメタボリックシンドロームおよびその構成因子との関連を明確にし、さらに食行動と社会心理要因との相互作用を確認する疫学研究を実施した。その結果、男性では、朝食欠食が体重増加に関連しており、特に睡眠時間が短いほどその関連が顕著であった。また肥満関連食行動数が多いほど、将来の2 型糖尿病発症リスクが高いことがわかった。ただし、肥満関連食行動が自覚的ストレスによりその後の体重変化に与える影響を分析したが、明確な影響は得られなかった。

2000～2001年の循環器健診を受診した40～79歳の大阪、秋田、茨城の地域住民(男性1,985人、女性3,677人)を対象としたコホート研究の結果、虚血性心疾患発症の年齢・地域調整ハザド比は、女性のインスリン分泌能指標低値群で8.9(1.1-72.4)(p=.04)と有意に高かった。これは、多変量調整後も9.1(1.1-77.0)(p=.04)と有意であり、血糖値正常域に限った場合でも年齢・地域調整HR8.1(1.0-68.0)(p=.05)、多変量調整HR7.2(0.8-62.0)(p=.07)と同様の傾向が認められた。脳卒中発症については、いずれも有意な関連は認められなかった。一方、2008年1月～2012年3月の40～79歳ドック受診者198人(男性96人、女性102人)を対象とした横断研究の結果、メタボリックシンドローム(MetS)の性・年齢調整オッズ比(OR)は、インスリン抵抗性有り群で13.5(3.7-48.7)であった。また、内臓脂肪面積過剰のORは、インスリン抵抗性有り群で4.9(2.4-10.0)、インスリン分泌能低下群で0.3(0.2-0.7)、同様に、脈波伝播速度高値のORは、3.2(1.5-6.7)、0.4(0.2-0.8)とそれぞれ有意な関連が認められた。

循環器ドック受診者520 人の約5 年間の追跡研究により、男女ともに、最大血圧値の血圧上昇が複数の血管部位の動脈硬化の進展に共通した危険因子であることが明らかとなりました。さらに男性では脂質異常(特にHDL コレステロールの低下)と糖代謝異常、女性では喫煙が動脈硬化進展の危険因子であることが示されました。すなわち、これらの危険因子の予防・防止が動脈硬化の悪化防止に有効である可能性が示されました。

社会心理要因に関する質問票、生化学的・生理学的指標等を用いた系統的な分析を行い、社会心理要因と少量～中等量の飲酒習慣の循環器疾患抑制効果のメカニズムを検証したところ、少量～中等量の飲酒者において社会的サポートの低い者で脳卒中抑制効果が認められない理由として、早朝血圧の高値とストレスの関与が推察された。

長期間疫学調査を実施してきた4地域(人口約60, 000人)の30～84歳男女において、1981年～2005年までの心臓突然死発症者数の推移を検討した。その結果、25年間で471人の心臓突然死が同定され、その年齢調整発症率は、1995年までは低下傾向が認められたが、1996年以降漸増傾向に転じた。また、男性および年齢が高い程発症率が高かった。 さらに、心臓突然死発症者の過去の健診成績をもとに発症に関わる要因について、Nestedcase-control studyにより前向きに検討した結果、高血圧、糖尿病、喫煙、心房細動、心電図ST-T異常、Wide QRS、心拍数の上昇は、それぞれ1. 5～3. 2倍の心臓突然死発症リスクの上昇と関連したが、肥満、脂質代謝異常については関連がみられなかった。

心理的因子と生活習慣、炎症、代謝異常、自律神経機能との関連を地域住民・職域にて検討した結果、身体活動が少ないこと、勤務時間が50時間以上/週であること、睡眠時間が6時間未満であることなどが3年後のうつ症状の出現と関連した。また、ストレスフルなライフイベント、怒り、慢性疲労、将来の希望の欠如などの心理的因子は炎症、代謝異常、自律神経機能と関連した。したがって、心理的因子は炎症・代謝異常・自律神経機能を介して循環器疾患のリスクの上昇と関連することが示唆された。