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Background: We aimed to evaluate the validity of self-administered questionnaire surveys and face-to-face interview surveys for the detection of Helicobacter pylori eradication therapy. Methods: Participants were a cohort, aged 40–74 years, living in three different locations of Japan, who took part in the baseline survey (2011–2012) of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Five years after the baseline survey, a questionnaire and interview survey were independently conducted to determine the history of Helicobacter pylori eradication treatment over the 5-year period. Prescription of Helicobacter pylori eradication medications in national insurance claims data from the baseline survey to the 5-year survey was used as a reference standard. Results: In total, 15,760 questionnaire surveys and 8,006 interview surveys were included in the analysis. There were 3,471 respondents to the questionnaire and 2,398 respondents to the interview who reported having received Helicobacter pylori eradication treatment within the past 5 years. Comparison of the questionnaire survey to national insurance claims data showed a sensitivity of 95.1% (2,213/2,328), specificity of 90.6% (12,174/13,432), positive predictive value of 63.8% (2,213/3,471), negative predictive value of 99.1% (12,174/12,289), and Cohen’s Kappa value of 0.71. Respective values of the interview survey were 94.4% (1,694/1,795), 88.7% (5,507/6,211), 70.6% (1,694/2,398), 98.2% (5,507/5,608), and 0.74. Conclusion: Both the questionnaire and the interview showed high sensitivity, high specificity, and good agreement with the insurance claim prescriptions data. Some participants may have received eradication treatment without going through the public insurance claim database, resulting in a low positive predictive value.

Background: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations. Methods: We used data from the baseline survey (2011–2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40–74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression. Results: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000 g (males 3.7%: females 0.8%). Among 88,653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500 g was associated with a higher prevalence of CVD (aPR 1.76; 95% CI, 1.37–2.26), hypertension (aPR 1.29; 95% CI, 1.17–1.42), and diabetes (aPR 1.53; 95% CI, 1.26–1.86) when a birth weight of 3,000–3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1,500–2,499 grams and 2,500–2,999 grams, while no significant associations were observed for birth weight at or over 4,000 grams. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout. Conclusion: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

Background: Associations of major risk factors for stroke with total and each type of stroke, as well as subtypes of ischemic stroke, and their population attributable fractions had not been examined comprehensively. Methods: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n = 14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (

Background: The association between hobby engagement and risk of dementia reported from a short-term follow-up study for individuals aged ≥65 years may be susceptible to reverse causation. We examined the association between hobby engagement in age of 40–69 years and risk of dementia in a long-term follow-up study among Japanese, including individuals in mid-life, when the majority of individuals have normal cognitive function. Methods: A total of 22,377 individuals aged 40–69 years completed a self-administered questionnaire in 1993–1994. The participants answered whether they had hobbies according to the three following responses: having no hobbies, having a hobby, and having many hobbies. Follow-up for incident disabling dementia was conducted with long-term care insurance data from 2006 to 2016. Results: During a median of 11.0 years of follow-up, 3,095 participants developed disabling dementia. Adjusting for the demographic, behavioral, and psychosocial factors, the multivariable hazard ratios of incident disabling dementia compared with “having no hobbies” were 0.82 (95% confidence interval [CI], 0.75–0.89) for “having a hobby” and 0.78 (95% CI, 0.67–0.91) for “having many hobbies”. The inverse association was similarly observed in both middle (40–64 years) and older ages (65–69 years). For disabling dementia subtypes, hobby engagement was inversely associated with the risk of dementia without a history of stroke (probably non-vascular type dementia), but not with that of post-stroke dementia (probably vascular type dementia). Conclusion: Hobby engagement in both mid-life and late life was associated with a lower risk of disabling dementia without a history of stroke.

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

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. Conclusion: 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 from 2011 through 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 1 year (

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

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.

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.

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.

Background: Lifestyle and life-environment factors have undergone drastic changes in Japan over the last few decades. Further, many molecular epidemiologic studies have reported that genetic, epigenetic, and other biomarker information may be useful in predicting individual disease risk. Methods: The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) was launched in 2011 to identify risk factors for lifestyle-related disease, elucidate factors that extend healthy life expectancy, and contribute toward personalized healthcare based on our more than 20 years’ experience with the JPHC Study. From 2011 through 2016, a baseline survey was conducted at 16 municipalities in seven prefectures across the country. A self-administered questionnaire was distributed to all registered residents aged 40–74, which mainly asked about lifestyle factors, such as socio-demographic situation, personal medical history, smoking, alcohol and dietary habits. We obtained informed consent from each participant to participate in this long follow-up study of at least 20 years, including consent to the potential use of their residence registry, medical records, medical fee receipts, care insurance etc., and to the provision of biospecimens (blood and urine), including genomic analysis. Results: As of December 31, 2016, we have established a population-based cohort of 115,385 persons (Response rate 44.1%), among whom 55,278 (47.9% of participants) have provided blood and urine samples. The participation rate was slightly higher among females and in the older age group. Conclusion: We have established a large-scale population-based cohort for next-generation epidemiological study in Japan.

Background: Few studies have investigated the effects of Okinawan vegetable consumption on the risk of incident stroke and coronary heart disease. This study aimed to examine associations of vegetable, fruit, and Okinawan vegetable consumption with risk of incident stroke and coronary heart disease in the Japanese population of Okinawa. Methods: The study design was a prospective cohort study. During 1995–1998, a validated food frequency questionnaire was administered in two study areas to 16,498 participants aged 45–74 years. In 217,467 person-years of follow-up until the end of 2012, a total of 839 stroke cases and 197 coronary heart disease cases were identified. Results: No statistically significant association between total Okinawan vegetable consumption and risk of stroke and coronary heart disease was obtained: the multivariable adjusted hazard ratios for the highest versus lowest tertile of consumption were 1.09 (95% confidence interval, 0.93–1.29; P for trend = 0.289) in model 2. Total vegetable and fruit and specific Okinawan vegetable consumption were also not statistically significantly associated with risk of cardiovascular outcomes. Conclusions: This study demonstrated that consumption of total vegetable and fruit, total Okinawan vegetables, and specific Okinawan vegetables in Japanese residents of Okinawa was not associated with risk of incident stroke and coronary heart disease.

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–

Background: The association between daily walking and pneumonia mortality, stratified by the presence of disease conditions, such as myocardial infarction (MI) or stroke, was investigated. Methods: The study participants were 22,280 Japanese individuals (9,067 men and 13,213 women) aged 65–79 years. Inverse propensity weighted competing risk model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for pneumonia mortality. Results: After a median of 11.9 years of follow-up, 1,203 participants died of pneumonia. Participants who did not have a history of MI or stroke and who walked for 1 hour/day or more were less likely to die from pneumonia (HR 0.90; 95% CI, 0.82–0.98) than those walked for 0.5 hours/day. A similar inverse association of pneumonia and walking (0.5 hours/day) was observed among participants with a history of MI (HR 0.66; 95% CI, 0.48–0.90). Among the participants with a history of stroke, those who walked for 0.6–0.9 hours/day were less likely to die because of pneumonia (HR 0.65; 95% CI, 0.43–0.98). Conclusions: Regular walking for ≥1 hour/day may reduce the risk of pneumonia mortality in elderly individuals with or without cardiovascular disease history.

The Circulatory Risk in Communities Study (CIRCS) is an ongoing community-based epidemiological study of lifestyle-related disease involving dynamic prospective cohorts of approximately 12,000 adults from five communities of Japan: Ikawa, Ishizawa and Kita-Utetsu (Akita Prefecture), Minami-Takayasu (Osaka Prefecture), Noichi (Kochi Prefecture), and Kyowa (Ibaraki Prefecture). One of the most notable features of CIRCS is that it is not only an observational cohort study to identify risk factors for cardiovascular diseases (CVD), such as stroke, coronary heart disease, and sudden cardiac death, but it also involves prevention programs for CVD. Using basic, clinical, epidemiological, and statistical techniques, CIRCS has clarified characteristics of CVD and the related risk factors to develop specific methodologies towards CVD prevention in Japanese middle-aged or older adults for more than half a century.

Background: Oxidative stress, the imbalance between pro- and antioxidants, has been implicated in the etiology and pathophysiology of the incidence and mortality of many diseases. We aim to investigate the relations of dietary intakes of vitamin C and E and main carotenoids with all-cause mortality in Japanese men and women. Methods: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk had 22,795 men and 35,539 women, aged 40–79 years at baseline (1988–1990), who completed a valid food frequency questionnaire and were followed up to the end of 2009. Results: There were 6,179 deaths in men and 5,355 deaths in women during the median follow-up of 18.9 years for men and 19.4 years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were 0.83 (95% confidence interval [CI], 0.76–0.90; P for trend < 0.0001) for vitamin C, 0.85 (95% CI, 0.78–0.93; P for trend < 0.0001) for vitamin E, 0.88 (95% CI, 0.81–0.96; P for trend = 0.0006) for β-carotene, and 0.90 (95% CI, 0.82–0.98; P for trend = 0.0002) for β-cryptoxanthin. The joint effect of any two of these highly correlated micronutrients showed significant 12–17% reductions in risk in the high-intake group compared with the low-intake group in women. These significant associations were also observed in the highest quintile intakes of vitamin C, vitamin E, and β-carotene in female non-smokers but were not observed in female smokers, male smokers, and non-smokers. Conclusions: Higher dietary intakes of antioxidant vitamins may reduce the risk of all-cause mortality in middle-aged Japanese women, especially female non-smokers.

Background: Because of the increasing number of mothers who continue to work after childbirth, participation in childcare has diversified. However, the impact of the main caregiver on children’s habits has not been determined. We sought to examine the effect of caregiver differences on childhood habituation of between-meal eating and body mass index (BMI). Methods: The Ibaraki Children’s Cohort Study involved 4592 Japanese children whose parents answered health questionnaires at age 3. Follow-up questionnaires were distributed to parents when children were 6 and 12 years old and to study subjects directly when they were 22 years old. We compared prevalence of between-meal eating and overweight as well as mean BMI at ages 6, 12, and 22 years, by their main daytime caregiver at age 3. Results: Compared to children cared for by mothers, those cared for by grandparents had a higher prevalence of between-meal eating before dinner for boys and girls at ages 6 and 12 years. At age 22 years, boys cared for by grandparents had a higher prevalence of overweight than those cared for by mothers (18.5% versus 11.2%, P = 0.037), but no such difference was noted in girls. However, both boys and girls cared for by grandparents had higher mean BMI over time than those cared for by mothers (coefficient = 0.47 kg/m2 for boys and coefficient = 0.35 kg/m2 for girls). Conclusions: Being cared for by grandparents at age 3 was associated with subsequent between-meal eating habits, being overweight, and increased mean BMI from childhood to adulthood.