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Background Breastfeeding is said to prevent overweight and obesity in childhood but the evidence about its long-term impact on body size into adolescence and adulthood is scarce. We sought to examine the association between feeding types and subsequent physical size at the ages of 3, 6, 12, and 22 years. Methods The Ibaraki Children's Cohort (IBACHIL) Study, which began in 1992, involved a cohort of 4,592 Japanese children from 87 communities of a single prefecture whose parents answered health questionnaires about their child's health and life habits at the age of 3 years. Follow-up questionnaires were distributed to the same cohort when they were 6, 12, and 22 years old. Self-reported height and weight, body mass index (BMI), and overweight status at ages of 3 (n = 4,290), 6 (n = 1,999; proportion of participants analyzed = 47%), 12 (n = 2,227; 52%), and 22 (n = 1,459; 34%) years were compared according to feeding type (breastfeeding, formula feeding, and mixed feeding) during infancy. Results At the age of 3 years, multivariable adjusted-mean weight and prevalence of overweight were less for breastfed children than those formula-fed in both boys (weight: 14.6 kg vs 14.7 kg, P = 0.07, overweight: 6.3% vs 9.3%, P = 0.03) and in girls (14.0 kg vs 14.2 kg, P = 0.01 and 10.4% vs 13.6%, P = 0.06). However, there were no statistically significant differences in weight, BMI, and overweight at the ages of 6, 12, and 22 years according to feeding type. Conclusions Breastfeeding may prevent overweight in childhood, but its impact is not significant in adolescence and adulthood.

BACKGROUND Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H.pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). METHODS A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples between 2011 and 2016. From these, treated (n=6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n= 22,420) formed the study population (n=28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than one year (

Aims Reports on the association between height and aortic disease have been modest, and there are only a few studies investigating the association between height and mortality from specific aortic disease types or by sex. Methods We conducted the Japan Collaborative Cohort Study, a prospective study of 99,067 Japanese (41,730 men and 57,337 women) aged 40-79 years old. Height was self-reported, and the participants were followed up from 1988-1989 to the end of 2009. Sex-specific hazard ratios (95% confidence intervals) of mortality from aortic disease type according to sex-specific quartiles of height were analyzed using the Cox proportional hazards model. Results During the median follow-up period of 19.1 years, the numbers of deaths due to aortic aneurysm, thoracic aortic aneurysm, abdominal aortic aneurysm, and aortic dissection were 87, 29, 48, and 56 among men and 35, 17, 15, and 65 among women, respectively. The sex-specific multivariate hazard ratios (95% confidence intervals) and p for trend for the highest versus lowest quartiles of height were 1.10 (0.66-1.83), p=0.58 among men and 1.54 (0.85-2.79), p=0.06 among women for total aortic disease; 1.85 (0.80-4.28), p=0.16 among men and 5.67 (0.90-35.77), p=0.08 among women for abdominal aortic aneurysm; and 1.13 (0.48-2.64), p=0.65 among men and 1.70 (0.82-3.50), p=0.04 among women for aortic dissection. The positive association was observed for both sexes, albeit more prominent among women. No association was found between height and mortality from thoracic aortic aneurysms. Conclusions As per our findings, we were able to determine that height was positively associated with mortality from abdominal aortic aneurysm in the Japanese population.

AIM Reports have shown that physical activity is inversely associated with heart failure risk, but evidence in Asian populations is lacking. We sought to examine the impacts of walking and sports participation on heart failure mortality among a Japanese population. METHODS We involved 36,223 Japanese men and 50,615 women (aged 40-79 years) who completed a self-administered questionnaire between 1988 and 1990. We divided participants into four categories of walking (＜0.5, 0.5, 0.6-1.0, and ≥ 1 h/day) and sports participation (＜1, 1-2, 3-4, and ≥ 5 h/week) and examined associations with activity and heart failure mortality through 2009. RESULTS We found inverse associations between physical activity and heart failure mortality. The multivariable hazard ratios (95% confidence intervals) for the highest category of walking time compared with the second-lowest category were 0.76 (0.59-0.99) in men and 0.78 (0.61-0.99) in women, while the ratios for the highest category of sports participation time compared with the second-lowest category were 0.62 (0.41-0.93) in men and 1.09 (0.73-1.65) in women. The lower hazard ratios in the highest categories of walking and sports participation time in men became no longer statistically significant after excluding heart failure deaths for the first 5, 10, and 15 years for walking time and 10 and 15 years for sports participation. However, in women, the low hazard ratios for the highest category ≥ 1.0 h/day of walking time did not change materially. CONCLUSIONS Physical activity was associated with a lower risk of mortality from heart failure in this Japanese community-based population. The attenuated and nonsignificant association of walking and sports participation with the risk in men after exclusion of first 5-15 years heart failure death was probably due to changes in physical activity and death certificate diagnosis during the follow-up and reverse causation. However, the persistent inverse association between walking and the risk in women suggests a beneficial preventive effect on heart failure.

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.

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 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; 95% CI, 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.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards’ models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06–1.38). The increased risk of cardiovascular mortality was particularly evident in women aged

Purpose To investigate whether and how unhealthy sleep habits (i.e., the frequency of difficulty falling or staying asleep, and the frequency of waking up tired) and the duration of sleep are related to the prevalence of dry eye disease (DED) in a general population. Methods This study included a total of 106,282 subjects aged 40–74 years who participated in a baseline survey of the Japan Public Health Center-based Prospective Study for the Next Generation. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Multivariable-adjusted logistic regression models were used to assess the relationships of various components of sleep status with DED. Results Higher frequencies of having difficulty falling or staying asleep, and waking up tired were significantly related to increased DED in both sexes (Ptrend Conclusions Sleep deprivation and poor sleep quality were significantly related to DED in a Japanese population.

ObjectiveTo examine whether the relationship between smoking cessation and risk of cardiovascular disease (CVD) was modified by weight gain.MethodsA total of 69 910 participants (29 650 men and 46 260 women) aged 45–74 years were grouped into six groups by smoking status in the first and 5-year surveys: sustained smokers, recent quitters according to postcessation weight gain (no weight gain, 0.1–5.0 kg, >5.0 kg), long-term quitters and never smokers. Quitting smoking within and longer than 5 years were defined as recent and long-term quitters, respectively. We used Cox proportional hazard models to estimate the HR for incident CVD, coronary heart disease (CHD) and stroke.ResultsWe identified 4023 CVDs (889 CHDs and 3217 strokes) during a median of 14.8 years of follow-up. Compared with sustained smokers, the multivariable HR (95% CI) for CVD was 0.66 (0.52 to 0.83) for recent quitters without weight gain, 0.71 (0.55 to 0.90) for recent quitters with weight gain of 0.1–5.0 kg, 0.70 (0.44 to 1.10) for recent quitters with weight gain of >5.0 kg, 0.56 (0.49 to 0.64) for long-term quitters, and 0.60 (0.55 to 0.66) for never smokers. The analysis restricted to men showed a similar association. Prespecified analysis by age suggested that recent quitters overall had a lower HR for CVD among those aged ConclusionsPostcessation weight gain did not attenuate the protective association between smoking cessation and risk of CVD.

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.

Aim The fact that low concentrations of high-density lipoprotein cholesterol are associated with the risk of cardiovascular disease is well known, but high-density lipoprotein metabolism has not been fully understood. Apolipoprotein A2 (ApoA2) is the second-most dominant apolipoprotein of high-density lipoprotein. We tested the hypothesis that ApoA2 isoforms are inversely associated with myocardial infarction. Methods We measured the plasma levels of three ApoA2 isoforms (ApoA2-ATQ/ATQ, ApoA2-ATQ/AT, ApoA2-AT/AT) in nested case-control study samples of 1:2 from the Japan Public Health-Center-based Study (JPHC Study): 106 myocardial infarction incidence cases and 212 controls. Results ApoA2-AT/AT was inversely associated with risk of myocardial infarction, in a matched model (OR, 2.78; 95% CI, 1.26-6.09 for lowest compared with the highest quartile), but its association was attenuated after adjustment for smoking only (OR=2.13; 95% CI, 0.91-4.97) or drinking only (OR=2.07; 0.91-4.74), and the multivariable OR was 1.20 (95% CI, 0.41-3.57). Neither ApoA2-ATQ/ATQ nor ApoA2-ATQ/AT was associated with the risk of myocardial infarction. Conclusions Our nested case-control study did not show a significant association of ApoA2 isoforms with a risk of myocardial infarction.

Background and aims The impact of weight changes in middle age on the incidence of cardiovascular disease has not been well elucidated. We investigated whether a 5-year weight change was associated with risk of stroke and coronary heart disease (CHD) in middle-aged individuals. Methods We analyzed data of 74,928 participants aged 40–69 years who provided responses to the baseline and 5-year follow-up questionnaires in the Japan Public Health Center–based Prospective Study. Weight change was calculated by subtracting self-reported weight at baseline from that at 5-year follow-up. Stroke and CHD events were confirmed by reviewing hospital records. Results During 997,406 person-years of follow-up, we documented 3,975 stroke and 914 CHD events. The multivariable HRs of stroke for losing ≥5 kg compared to stable weight (change ≤2 kg) was 1.17 (95% CI, 1.01–1.37) in men versus 1.33 (1.13–1.57) for losing ≥5 kg and 1.61 (1.36–1.92) for gaining ≥5 kg in women (U-shaped association). These associations did not change after the exclusion of early events. The multivariable HR of CHD for gaining ≥5 kg was 1.22 (0.95–1.58) in men. After exclusion of early events within another 5 years, that positive association became stronger [multivariable HR 1.34 (1.00–1.82)]. Conclusions Weight gain during middle age was associated with an increased risk of stroke in women and an increased risk of CHD in men. Weight loss was associated with an increased risk of stroke in both men and women.

Aims: Reports on an association between body mass index and aortic disease, which remains controversial. This study investigated the association between body mass index and mortality from aortic disease. Methods: We conducted the Japan Collaborative Cohort Study, a prospective study of 103,972 Japanese men and women aged 40–79 years. Body mass index was calculated on the basis of self-reported height and weight, and the participants were followed up from 1988–89 through 2009. Sex-specific hazard ratios (95% confidence intervals) of mortality from aortic disease according to quintiles of body mass index were analyzed using the Cox proportional hazards model. Results: During the median 18.8 years of follow-up, we documented 139 deaths due to aortic aneurysm (including 51 thoracic and 74 abdominal aortic aneurysms) and 134 deaths due to aortic dissection. We observed positive associations of body mass index with mortality from aortic aneurysm among men: the multivariable hazard ratios (95% confidence intervals) for highest versus lowest quintiles of body mass index were 4.48 (2.10–9.58), P for trend < 0.0001 for aortic aneurysm; 6.52 (1.33–32.02), P = 0.005 for thoracic aortic aneurysm; 3.81 (1.39–10.49), P = 0.01 for abdominal aortic aneurysm; and 2.71 (1.59–4.62), P = 0.001 for total aortic disease. No association was found for aortic dissection. Among ever-smokers (men ≥ 90%) but not never-smokers (women ≥ 84%), an association between body mass index and aortic disease mortality was observed regardless of sex, which may explain the sex difference (P for sex-interaction = 0.046). Conclusions: We found a positive association between body mass index and mortality from aortic aneurysm among Japanese men and smokers.

This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (

Background: The frequency of laughter has been associated with cardiovascular disease and related biomarkers, but no previous studies have examined association between laughter and changes in blood pressure levels. We sought to identify temporal relationships between frequency of laughter in daily life and systolic and diastolic blood pressure changes in participants from 2010 through 2014. Methods: Participants were 554 men and 887 women aged 40–74 years who answered self-administered questionnaire quantifying frequency of laughter at baseline. We measured participant blood pressure levels twice using automated sphygmomanometers for each year from 2010 to 2014. The associations between laughter and changes in blood pressure over time were analyzed using linear mixed-effect models. Results: There was no significant difference in blood pressure according to frequency of laughter at baseline in either sex. Men with frequency of laughter 1 to 3 per month or almost never had significantly increased systolic and diastolic blood pressure levels over the 4-year period (time-dependent difference: 0.96 mm Hg (95% confidence interval [CI], −0.2 to 1.8; P = 0.05). Changes in blood pressure associated with infrequent laughter (ie, 1 to 3 per month or almost never) were evident in men without antihypertensive medication use over 4 years (0.94 mm Hg; 95% CI, −0.2 to 2.0; P = 0.09) and men who were current drinkers at baseline (1.29 mm Hg; 95% CI, −0.1 to 2.3; P = 0.04). No significant difference was found between frequency of laughter and systolic (0.23 mm Hg; 95% CI, −1.0 to 1.5; P = 0.72) and diastolic (−0.07 mm Hg; 95% CI, −0.8 to 0.7; P = 0.86) blood pressure changes in women. Conclusions: Infrequent laughter was associated with long-term blood pressure increment among middle-aged men.

To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009. A total of 45,837 male residents were observed for a median period of 19.1 years. Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019. During follow-up, 268 participants died from COPD. The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41–0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59–0.68). These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years. Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality.

Purpose This study compared working cancer survivors’ self-rated health status (SRHS), physical functional capacity, depressive symptoms, and happiness to those of cancer-free workers. Methods A nationwide general population-based cross-sectional study on a sample of Japanese was conducted. Prevalence of deteriorated SRHS, restricted physical functional capacity, depressive symptoms, and perceived happiness were compared between working cancer survivors and cancer-free workers with multivariable logistic regression analysis adjusted for age and sociodemographic and health-related backgrounds. Results Of the 28,311 male and 26,068 female workers, 977 (3.5%) and 1267 (4.9%) were cancer survivors, respectively. Working cancer survivors reported deteriorated SRHS more frequently than cancer-free workers: 21.3% vs. 13.8%, multivariable-adjusted odds ratio (95% confidence interval), 1.64 (1.39–1.95) for men, 23.8% vs. 17.5%, 1.34 (1.16–1.54) for women. Restricted physical functional capacity was reported more frequently in working cancer survivors than cancer-free workers: 6.8% vs. 2.6%, 1.76 (1.34–2.32) for men, 4.9% vs. 2.0%, 2.06 (1.56–2.71) for women. No significant difference was found for depressive symptoms: 21.6% vs. 22.9% in men, 30.0% vs. 28.5% in women. Working cancer survivors felt happiness more frequently than cancer-free survivors in men (77.3% vs. 71.7%, 1.21 (1.01–1.45)) but not in women (76.1% vs. 74.9%). Conclusions Working cancer survivors had worse SRHS and more restricted physical functional capacity than cancer-free workers. In men, working cancer survivors felt happiness more frequently than cancer-free workers. Implications for Cancer Survivors Continuous support to improve cancer survivors’ SRHS and physical functional capacity would be necessary even while they are working.

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.

Aim: The association between atrial fibrillation (AF) and risk of stroke mortality among men and women without traditional cerebrocardiovascular risk factors (TCVRFs) is unclear. This study aimed to determine whether AF was a risk factor for stroke and total cardiovascular disease mortality among individuals without TCVRFs. Methods: A total of 90,629 Japanese subjects from the Ibaraki Prefectural Health Study aged 40–79 years, with and without TCVRFs, were studied from 1993 to 2013. Hazard ratios (HRs) were calculated using the Cox proportional hazard regression model stratified by sex and the presence of TCVRFs. Covariates were age, systolic blood pressure, anti-hypertensive medication use, and serum total cholesterol levels. A standard 12-lead electrocardiogram at rest was used to screen AF. Cause-specific mortality was classified according to the International Classification of Disease code. Results: Compared with participants without AF, multivariable-adjusted hazard ratios (with 95% confidence intervals) for stroke mortality among participants without TCVRFs were 4.3 (1.1–17.8) and 15.0 (5.5–40.8) for men and women with AF, respectively. HRs for total cardiovascular disease mortality were 6.2 (2.8–14.2) for men and 10.7 (4.8–24.1) for women. For participants with TCVRFs, multivariable-adjusted HRs for stroke mortality were 3.1 (2.2–4.6) and 4.3 (2.6–7.3), whereas HRs for total cardiovascular disease mortality were 2.9 (2.2–3.8) and 3.5 (2.4–5.1) for men and women, respectively. Conclusions: AF was found to be an independent risk factor for stroke and total cardiovascular mortality even in individuals without other TCVRFs.

Seaweeds contain minerals, vitamins, soluble dietary fibers, and flavonoids, which are regarded as preventive agents against lifestyle-related diseases. Seaweeds are consumed commonly in East Asian countries including Japan. Thus, intake of seaweeds might contribute to Japanese longevity via prevention of lifestyle-related diseases. Recently, two large Japanese cohort studies have reported the association of seaweed intake with reduced risk of cardiovascular diseases. On the other hand, seaweeds also contain iodine and heavy metals such as arsenic species, which are considered to have adverse effects on health. We here reviewed studies of the association between seaweed intake and mortality from or incidence of cancer and cardiovascular diseases, and their risk factors such as blood pressure or serum lipids. We also summarized the adverse effects of iodine and arsenic species in seaweeds. Although seaweeds have not been widely consumed in Western countries, dietary diversification and an increased proportion of immigrants from East Asia may increase seaweed consumption in those countries. Further epidemiological studies including observational and interventional studies are necessary to clarify the effects of seaweeds on disease and health.

Background Few studies examining the impact for women of employment status on health have considered domestic duties and responsibilities as well as household socioeconomic conditions. Moreover, to our knowledge, no studies have explored the influence of work-family conflict on the association between employment status and health. This research aimed to investigate the cross-sectional associations between employment status (regular employee, non-regular employee, or self-employed) with self-rated health among Japanese middle-aged working women. Methods Self-report data were obtained from 21,450 working women aged 40-59 years enrolled in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study) in 2011-2016. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for poor self-rated health ('poor' or 'not very good') by employment status. Sub-group analyses by household income and marital status, as well as mediation analysis for work-family conflict, were also conducted. Results Adjusted ORs for the poor self-rated health of non-regular employees and self-employed workers were 0.90 (95% CI, 0.83-0.98) and 0.84 (95% CI, 0.75-0.94), respectively, compared with regular employees. The identified association of non-regular employment was explained by work-family conflict. Subgroup analysis indicated no statistically significant modifying effects by household income and marital status. Conclusion Among middle-aged working Japanese women, employment status was associated with self-rated health; non-regular employees and self-employed workers were less likely to report poor self-rated health, compared with regular employees. Lowered OR of poor self-rated health among non-regular employees may be explained by their reduced work-family conflict.

The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan. We studied 79,648 participants (42,788 women; 36,860 men) aged 45–74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995–1998) and were followed to 2009–2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products. In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes. Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women.

Objective The burden of death from pneumonia is expected to increase with the aging of the population, as has been observed in Japan. Depressive tendency, a common psychosocial sign, may be a risk factor for pneumonia due to its possible association with some immune dysfunction. This study aimed to clarify the association between depressive tendency and the risk of death from pneumonia. Methods A population-based cohort that consisted of 75,174 Japanese men and women was followed for a median of 19.1 years. Four psychological and behavioral symptoms (depressive symptoms) were used to evaluate depressive tendency. Results A total of 1,329 deaths from pneumonia were observed. Depressive symptoms were positively and dose-dependently associated with the risk of death from pneumonia (p

Aim N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese. Methods We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (＜55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes. Results During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14-28.0) for ischemic stroke and 6.81 (1.11-41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes. Conclusion We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.

Aim A positive association between non-high-density lipoprotein cholesterol (non-HDL-C) and coronary heart disease (CHD) has been established; however, associations between non-HDL-C and stroke subtypes have not been determined. Methods We conducted a prospective study of 30,554 individuals aged 40-69 yrs with no history of cardiovascular disease (CVD) in Japan. Sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of stroke subtypes and CHD were estimated according to quintiles of non-HDL-C, using Cox proportional hazard models adjusted for other established risk factors. Results We identified 1,705 stroke and 296 CHD events over a median 15 yrs of follow-up. The fractional polynomials analysis revealed a U-shaped association between non-HDL-C and stroke risk in men. When analyzed for stroke subtypes, the data revealed an inverse relationship between non-HDL-C and intracerebral hemorrhage (ICH), primarily with lobar ICH, and a positive association between non-HDL-C and large-artery occlusive infarction in men [adjusted HR 0.55 (95% CI, 0.35-0.87) and 2.05 (95% CI, 1.07-3.93) for the highest and lowest quintile of non-HDL-C, respectively]. The lowest risk of ICH in women was observed in the fourth quintile, and the lowest risk of embolic infarction was observed in the third quintile. In contrast, non-HDL-C was positively associated with CHD in both sexes. Conclusions In Japanese men, lower non-HDL-C levels were associated with a decreased risk of large-artery occlusive infarction and an increased risk of ICH, particularly lobar ICH.

Although a meta-analysis previously suggested a positive relationship between diabetes and intraocular pressure (IOP), the interrelationships among diabetes, IOP, and other ocular biometric parameters remain unclear. The present study investigated the relationships of diabetes, haemoglobin A1c (HbA1c), and serum glucose with IOP and ocular hypertension (IOP > 21 mmHg) in non-glaucomatous Japanese adults living in Chikusei City. Diabetes was defined as a self-reported history of diabetes, the use of antidiabetic medication, or HbA1c levels ≥6.5%. Among 6,786 enrolled participants aged 40 years and above, 734 were classified as diabetic (10.8%). After adjusting for several confounders, the IOP values were significantly higher in participants with diabetes than in those without diabetes (14.4 ± 0.1 vs. 13.9 ± 0.1 mmHg, P

Background. Recently, chronic hepatitis E has been reported in solid organ transplant (SOT) recipients in European countries. Previously, we clarified the prevalence of hepatitis E virus (HEV) infection in Japanese liver transplant recipients and identified 2 chronic hepatitis E patients infected by blood transfusion. However, the rate of HEV infection in recipients of SOTs other than liver in Japan remains unclear, so we conducted a nationwide survey to clarify the prevalence of chronic HEV infection in Japanese heart and kidney transplant recipients. Methods. A total of 99 heart and 2526 kidney transplant recipients in 17 hospitals in Japan were examined for the presence of the IgG class of anti-HEV antibodies as well as for serum HEV RNA. Results. The prevalence of anti-HEV IgG among heart and kidney transplant recipients was 7.07% (7/99) and 4.08% (103/2526), respectively. One heart transplant patient (1.01%) and 11 kidney transplant patients (0.44%) were found to be positive for HEV RNA. The HEV isolates from all viremic patients were typed as genotype 3. Four patients developed chronic hepatitis E after transplantation. Three patients were treated with ribavirin; their liver enzymes normalized, and HEV RNA became negative immediately. Sustained virologic response was achieved in all cases. Conclusions. This is the first nationwide survey of HEV infection in Japanese heart and kidney transplant recipients. The prevalence of anti-HEV IgG and HEV RNA in heart and kidney transplant recipients in Japan was lower than that in European countries. Of note, 42% of viremic transplant patients developed chronic hepatitis.

The role of serum uric acid as a predictor of stroke among the general Japanese population remains controversial. We conducted a prospective cohort study of 5235 men and 8185 women aged 40-79 years at baseline between 1985 and 1994 in four Japanese communities, who were initially free from stroke, coronary heart disease, and medication for hyperuricemia or gout. Cox proportional hazards models were used to estimate sex-specific hazard ratios of stroke and its types in relation to serum uric acid level. During a median follow-up of 23.1 years, we recorded 1018 (488 men and 530 women) incident strokes, including 222 (99 and 123) intraparenchymal hemorrhages, 113 (33 and 80) subarachnoid hemorrhages and 667 (347 and 320) ischemic strokes. After adjustment for age, community and known cardiovascular risk factors, the multivariable hazard ratios (95% CIs) in the highest vs. lowest quintile of serum uric acid were 1.45 (1.07-1.96) for total stroke, 1.20 (0.65-2.20) for intraparenchymal hemorrhage, 1.46 (0.69-3.09) for subarachnoid hemorrhage and 1.61 (1.07-2.41) for ischemic stroke in women. The corresponding multivariable hazard ratios (95% CIs) in men were 1.02 (0.74-1.35), 0.83 (0.40-1.72), 1.19 (0.38-3.75) and 1.00 (0.70-1.41). Furthermore, those positive associations with risks of total and ischemic strokes in women were more evident in nonusers of antihypertensive medication than the users. In conclusion, elevated serum uric acid level is an independent predictor of total stroke in women but not in men. The positive association in women was mostly attributable to ischemic stroke and was more pronounced among nonusers of antihypertensive medication.

Purpose This population-based, cross-sectional study was performed to assess the influence of life-style modalities, including physical activity, sedentary behaviors, and visual display terminal (VDT) use, on the prevalence of dry eye disease (DED). Methods The study included a total of 102,582 participants aged 40–74 years, from the Japan Public Health Center-based Prospective Study for the Next Generation, a large nationwide prospective ongoing Japanese cohort study. Logistic regression analyses were used to investigate the relationship of total and leisure-time physical activity, duration of sedentary behaviors, and VDT use (hours/day) with DED. Results Among 47,346 men and 55,236 women, 25,234 (8315 males and 16,919 females) cases of DED were documented. Total physical activity was significantly related to decreased DED in both sexes; for the highest vs. lowest total physical activity quartiles, the multivariable-adjusted odds ratios (ORs) for DED were 0.90 (95% confidence interval [CI], 0.84–0.97; Ptrend Conclusions Physical inactivity, prolonged sedentary behaviors, and use of VDT were related to increased susceptibility to DED among middle-aged to older Japanese adults.

The association of chocolate consumption with risk of gestational diabetes has not been examined. We aimed to investigate the prospective association between chocolate consumption and risk of gestational diabetes in a large birth cohort in Japan. A total of 97 454 pregnant women with a median gestational age of 12 weeks were recruited from January 2011 to March 2014. Data on demographic information, disease history, socio-economic status, lifestyle and dietary habits were obtained at the study enrolment. Dietary intake during the past 12 months before study enrolment was assessed through a semi-quantitative FFQ. The logistic regression was used to obtain the OR of gestational diabetes in relation to chocolate consumption. Among 84 948 women eligible for the analysis, 1904 cases of gestational diabetes (2·2 %) were identified during the period of pregnancy. After controlling for potential confounding factors including age, smoking status, drinking status, education level, occupation, pre-pregnant BMI, depression, previous history of macrosomia babies, parity, physical activity and dietary factors, women in the highest quartile of chocolate consumption, compared with those in the lowest quartile, had a significantly lower risk of developing gestational diabetes (OR 0·78, 95 % CI 0·67, 0·90; P for trend = 0·002). Stratified analyses suggested that the association was not significantly modified by pre-pregnancy BMI, age, parity, smoking status or drinking status. The present prospective cohort study provided evidence that chocolate consumption was associated with a significant lower risk of gestational diabetes in Japanese women.

Background The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. Objectives We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease risk among a Japanese study population. Methods We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40-69 y). Seaweed intake was determined by FFQ at baseline (1990-1994). Incidences of stroke and ischemic heart disease were ascertained until the end of 2009 (Cohort I) or 2012 (Cohort II). Sex-specific cardiovascular disease HRs (95% CIs) were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors. Results During 1,493,232 person-years of follow-up, 4777 strokes (2863 ischemic stroke, 1361 intraparenchymal hemorrhages, and 531 subarachnoid hemorrhages) and 1204 ischemic heart disease cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption compared with almost no consumption of seaweed were seen in ischemic heart disease [0.76 (0.58, 0.99); P-trend = 0.04] and total cardiovascular diseases [0.88 (0.78, 1.00); P-trend = 0.08]. Among women, such inverse associations were 0.56 (0.36, 0.85; P-trend = 0.006) for ischemic heart disease and 0.89 (0.76, 1.05; P-trend = 0.10) for total cardiovascular diseases. No significant associations were observed between seaweed intake and risk of total stroke or stroke types among either men or women. Conclusions Seaweed intake was inversely associated with risk of ischemic heart disease.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

Aim Diabetes mellitus and hypertriglyceridemia may adversely interact with the development of ischemic cardiovascular disease, but epidemiological evidence on this issue is scarce. We hypothesized that the impact of hypertriglyceridemia on ischemic cardiovascular disease (ischemic heart disease and ischemic stroke) would differ according to the presence or absence of diabetes mellitus and tested our a priori hypothesis under a large population-based prospective study. Methods A total of 90,468 men and women aged 40-79 years in 1993 were enrolled in the Ibaraki Prefectural Health Study (IPHS), a community-based cohort study of Japanese. The participants' serum triglyceride levels (mostly nonfasting) were measured every 5 years, and the participants were followed up for mortality from ischemic cardiovascular disease through 2016. Hazard ratios (95% confidence intervals) were calculated according to 5-year updated triglyceride levels (＜100, 100-149, 150-199, 200-299, and ≥ 300 mg/dl). Results During 1,795,877 person-years, there were 3,323 deaths from ischemic cardiovascular diseases (1,968 ischemic heart diseases and 1,355 ischemic strokes). We found no association between triglyceride levels and the risk of mortality from ischemic cardiovascular disease after adjustment for known cardiovascular risk factors. However, when stratified by the presence or absence of diabetes mellitus, excess mortality from ischemic cardiovascular disease appeared among participants with diabetes mellitus with triglyceride levels of ≥ 300 mg/dl. Further adjustment for high-density lipoprotein-cholesterol attenuated the association toward being statistically nonsignificant. Conclusion The impact of high serum triglyceride levels on the risk of ischemic cardiovascular disease mortality was confined to participants with diabetes mellitus.

Background Folate regulates homocysteine metabolism and high blood homocysteine level has been associated with risk of dementia. Accordingly, serum folate is hypothesized to decrease the risk of dementia but epidemiological evidence, especially for Japanese, is scant. The aim of this study was to examine associations between serum folate and risk of disabling dementia within a Japanese cohort over 20 years of follow-up. Methods We performed an intracohort case-control study nested in a community-based cohort, the Circulatory Risk in Communities Study (CIRCS), involving 13934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 511 cases of incident disabling dementia, and in 1022 controls whose age (±1 years), sex, area, 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 Serum folate was inversely associated with risk of disabling dementia. The multivariate odds ratios (95% confidence intervals) were 0.62(0.43-0.88), 0.71(0.49-1.00), 0.63(0.43-0.91), and 0.51(0.34-0.76) for persons with the second, third, fourth, and highest quintiles of serum folate, respectively, compared with the lowest quintiles (P for trend = 0.19). Conclusions Low serum folate level was associated with increased risk of disabling dementia among Japanese. Key messages e Low folate intake may have an adverse effect on developing dementia.

Background The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease (IHD) risk among a Japanese study population. Methods We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake in the study subjects was estimated from the food frequency questionnaire at baseline (1990–1994). Stroke and IHD events were identified until the end of 2009 (Cohort I) or 2012 (Cohort II). The hazard ratios (HRs) (95% confidence intervals [CIs]) for incident cardiovascular disease (CVD) and its subtype were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors by sex. Results During 1,493,232 person-years of follow-up, 4,777 strokes and 1,204 IHD cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption were seen in IHD (0.76 [0.58-0.99]; P-trend=0.04) compared to almost no seaweed consumption. Among women, such inverse associations were observed in incident IHD (0.56 [0.36-0.85]; P-trend=0.006). No significant associations were observed between seaweed intake and risk of stroke nor stroke subtypes among either men or women. Conclusions Seaweed intake has been shown to contribute to the prevention of IHD in a large Japanese cohort. Key messages Seaweed intake could be beneficial for prevention of IHD.

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke, transient ischemic attack , diabetes mellitus (DM), cardiovascular disease , chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than that of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

BACKGROUND Both short and long interpregnancy intervals (IPIs) have been associated with risk of preterm birth, but the evidence is limited in Asians. It is also uncertain whether the association is modified by dietary folate intake or folic acid supplementation during pregnancy. Thus, we examined associations between IPI and risk of preterm birth, and effect modification of those associations by dietary intake of folate and supplementation with folic acid on the basis of a nationwide birth cohort study. METHODS Among 103,062 pregnancies registered in the Japan Environment and Children's Study, 55,203 singleton live-birth pregnancies were included in the analysis. We calculated IPI using birth date, gestational age at birth of offspring, and birth data of the latest offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) of the risk of preterm birth were estimated according to IPI categories. RESULTS Both

Objective To investigate the relation between body mass index (BMI) and dry eye disease (DED). Methods We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women. Results Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women. Conclusions This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

General population-based cohort studies provide solid evidence on mass Helicobacter pylori (HP) eradication effects. Self-reported questionnaires are occasionally used in such studies to ascertain the HP eradication history. However, reports on the reliability of these questionnaires are lacking. This general population-based cohort study included 899 individuals with HP infection at the baseline survey who were reported to have eradicated it at the 5-year follow-up survey. Of these, the medical records of 280 patients were available for investigation, and the HP eradication status of 93 individuals was ascertained. Their medical records were reviewed, and the reliability of the self-reported questionnaire responses was assessed. Of the 91 individuals who successfully eradicated HP based on the medical records, 90 (98.9%) answered the self-reported questionnaire correctly, with an unweighted kappa value of 0.661 (p

Introduction: Chronic low back pain (CLBP), defined as low back pain persisting for at least 3 months, leads to limitations in the activities of daily living and decreased quality of life. Individualized self-exercise education could be a preferable treatment option, especially in community-dwelling people with CLBP. Previous studies, however, did not directly compare the effects of therapist-led self-exercise education and material-only education, and there are only a few studies investigating the effects of low-dose (comprising a few sessions) self-exercise education on CLBP. We present a protocol of community-based, randomized study to evaluate the effects of low-dose (comprising a few sessions), therapist-led self-exercise education on CLBP. Methods: Forty-eight participants with CLBP (men and women, aged 40-74 years) will be allocated to therapeutic self-exercise education programs, either a therapist-led group (2-week therapist's consultation and material use) or material-only group (material use only), in a randomized controlled trial. Pain intensity (NRS, numeric rating scale), pain disability (RDQ, Roland-Morris disability questionnaire), pain self-efficacy (PSEQ, pain self-efficacy questionnaire), and quality of life score (EQ-5D, European quality of life-5 dimensions) will be measured at baseline and at 4, 12, and 24 weeks. We will apply a repeated-measures design with mixed-effect models to estimate group differences from the baseline. Ethics/Trial registration number: The protocol was approved by the Ethics Committees of the Osaka Center for Cancer and Cardiovascular Disease Prevention and Osaka University. The trial registration number is registered on the University Hospital Medical Information Network (UMIN000024537).

Background: The association of body mass index (BMI) with risks of ischemic stroke subtypes have not been established. Methods: Cumulative average BMI was calculated using self-reported body weight and height obtained from baseline (Cohort I in 1990, and Cohort II from 1993–1994) and 5- and 10-year questionnaire surveys of Japan Public Health Center-based prospective (JPHC) study. A total of 42,343 men and 46,413 women aged 40–69 years were followed-up for the incidence of lacunar, large-artery occlusive, and cardioembolic strokes. A sub-distribution hazard model was used to estimate sub-distribution hazard ratios (SHRs) and the 95% confidence intervals (CIs). Results: During a median of 20.0 years of follow-up, we documented 809 and 481 lacunar, 395 and 218 large-artery occlusive, and 568 and 298 cardioembolic strokes in men and women, respectively. After adjustment for baseline age, updated smoking, alcohol consumption, leisure-time physical activity, and histories of hypertension, dyslipidemia, and diabetes mellitus, cumulative average BMI was positively linearly associated with lacunar (trend P = 0.007), large-artery occlusive (trend P = 0.002), and cardioembolic (trend P < 0.001) strokes in men, and with lacunar (trend P < 0.001) and large-artery occlusive (trend P = 0.003) strokes in women. There were approximately two-fold excess risk of cardioembolic stroke in both sexes and of lacunar and large-artery occlusive strokes in women for cumulative average BMI ≥30 kg/m2 compared to BMI 23–

Summary Background & aims Many studies have suggested that fish intake is associated with protection from risk of atherosclerotic diseases; however, this association with aortic diseases has not been elucidated worldwide. We hypothesized that fish intake is inversely associated with mortality from aortic diseases (aortic dissection and aneurysm). Methods The study was conducted as a pooled analysis of original data from a maximum of 8 cohort studies, comprising a total of 366,048 community-based men and women who had no history of cardiovascular disease or cancer. In each cohort, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality from aortic dissection, aneurysm and total aortic disease according to the frequency of fish intake and estimated summary HRs derived from each study. Results Nonlinear inverse associations were found between fish intake and total aortic disease. Compared with persons who ate fish 1–2 times/week, persons who seldom ate fish had higher mortality from total aortic disease (multivariable-adjusted pooled HR = 1.93; 95% CI, 1.13–3.31). Higher mortality was not seen in those who ate fish 1–2 times/month. A similar pattern was observed for aortic dissection. Regarding aortic aneurysm, both persons who seldom ate fish and those who ate fish 1–2 times/month had higher mortality (HR = 1.99; 95% CI, 0.90–4.40 and HR = 1.86; 95% CI, 0.87–3.98, respectively). Conclusions Persons who seldom ate fish had higher mortality from aortic dissection, aneurysm, and total aortic diseases.

To investigate whether social support and social trust are associated with DED.Cross-sectional data from the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) were used. Subjects are 96,227 Japanese men and women aged 40 to 74. Data from respondents included information on DED, social support and social trust. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Social support was measured by emotional support and tangible support. Social trust was measured by level of general trust in others. Multiple logistic regression analysis was conducted to assess the association of social determinants for DED.Individuals with high levels of social support and social trust were less likely to have severe symptoms of DED and clinically diagnosed DED (P for trend 0.001 in both cases). Those with the highest levels of social support and social trust were least likely to have DED (odds ratios [OR] = 0.64 [0.61-0.67], 95% confidence interval [CI] = 0.63 [0.60-0.67] for severe symptoms of DED; OR = 0.88 [0.83-0.93] and 0.85 [0.80-0.91] for clinically diagnosed DED).High levels of social support and social trust were associated with a lower prevalence of DED.

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.

BACKGROUND Although prevalence of low birth weight has increased in the last 3 decades in Japan, no studies in Japanese women have investigated whether birth weight is associated with the risk of pregnancy complications, such as pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM). METHODS We used data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT), a population-based cohort study in Japan that launched in 2011. In the main analysis, we included 46,365 women who had been pregnant at least once, for whom information on birth weight and events during their pregnancy was obtained using a self-administered questionnaire. Women were divided into five categories according to their birth weight, and the relationship between birth weight and risk of PIH and GDM was examined using multilevel logistic regression analyses with place of residence as a random effect. RESULTS Compared to women born with birth weight of 3,000-3,999 grams, the risk of PIH was significantly higher among women born

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.

Little is known about the risk of cerebrovascular disease in cancer survivors. We aimed to assess the association between incident cancer and the subsequent risk of stroke using a large-scale, population-based prospective study. 74,530 Japanese aged between 40 and 69 years at baseline study were matched by the status of cancer diagnosis during follow-up using propensity score nearest-neighbor matching with allowance for replacement. A total of 2242 strokes were reported during 557,885 person-years of follow-up. Associations between incident cancer and the subsequent risk of all strokes, cerebral infarction, and intracerebral hemorrhage were assessed using a Cox proportional hazards model stratified on the propensity score-matched pairs. No significant association was observed between the status of cancer diagnosis of all types, gastric, colorectal and lung cancer, and subsequent occurrence of all strokes, cerebral infarction, and intracerebral hemorrhage. However, analysis by discrete time periods suggested an elevated risk in cancer patients for one to three months after a cancer diagnosis in all stroke (HR, 2.24; 95% CI, 1.06, 4.74) and cerebral infarction (HR, 2.62; 95% CI, 1.05, 6.53). This prospective cohort study found no association between the status of cancer diagnosis and the subsequent occurrence of all strokes and its subtypes during the entire follow-up period but suggested an increase in stroke risk during the active phase of malignancy.