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This work was supported by Grants-in-Aid for Scientifc Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (Monbusho); Grants-in-Aid for Scientifc Research on Priority Areas of Cancer; and Grants-in-Aid for Scientifc Research on Priority Areas of Cancer Epidemiology from MEXT (MonbuKagaku-sho) (nos. 61010076, 62010074, 63010074, 1010068, 2151065, 3151064, 4151063, 5151069, 6279102, 11181101, 17015022, 18014011, 20014026, 20390156, and 26293138); by JSPS Kakenhi grant number JP16H06277; and by a grant-in-aid from the Ministry of Health, Labour and Welfare, Health and Labor Sciences research grants, Japan (Research on Health Services: H17–Kenkou–007; Comprehensive Research on Cardiovascular Disease and Life–Related Disease: H18–Junkankitou [Seishuu]–Ippan–012; H19–Junkankitou [Seishuu]–Ippan–012; H20–Junkankitou [Seishuu]–Ippan–013; H23–Junkankitou [Seishuu]–Ippan–005; H26-Junkankitou [Seisaku]-Ippan-001); H29–Junkankitou [Seishuu]–Ippan–003 and 20FA1002).

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

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

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.

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.

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.

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.

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

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

Although high or low (no) meat consumption was associated with elevated or reduced mortality from cardiovascular disease, respectively, few studies have investigated the association between moderate meat consumption and cardiovascular disease. We aimed to evaluate the associations between moderate meat consumption and cardiovascular disease mortality.We conducted a prospective cohort study of 51,683 Japanese (20,466 men and 31,217 women) aged 40-79 years living in all of Japan (The Japan Collaborative Cohort Study; JACC Study). Consumptions of meat (beef, pork, poultry, liver and processed meat) were assessed via a food frequency questionnaire administrated at baseline survey. Hazard ratios (HRs) of mortality from cardiovascular disease were estimated from Cox proportional hazards regression models according to quintiles of meat consumption after adjustment for potential confounding variables.During 820,076 person-years of follow-up, we documented 2685 deaths due to total cardiovascular disease including 537 ischemic heart diseases and 1209 strokes. The multivariable HRs (95% confidence interval) for the highest versus lowest quintiles of meat consumption (77.6 versus 10.4 g/day) among men were 0.66 (0.45-0.97) for ischemic heart disease, 1.10 (0.84-1.43) for stroke and 1.00 (0.84-1.20) for total cardiovascular disease. The corresponding HRs (59.9 versus 7.5 g/day) among women were 1.22 (0.81-1.83), 0.91 (0.70-1.19) and 1.07 (0.90-1.28). The associations were similar when the consumptions of red meat, poultry, processed meat and liver were examined separately.Moderate meat consumption, up to ~100 g/day, was not associated with increased mortality from ischemic heart disease, stroke or total cardiovascular disease among either gender.

In Japan, overweight/obesity in adults defined as a body mass index of 25 kg/m(2) or over has roughly doubled among middle-aged men over the past few decades. In parallel with a population rightward shift in the degree of obesity, the proportion of hypertension attributed to overweight has increased. There is an indication that the incidence of ischemic stroke and coronary heart disease remains stable or has been increasing among men. These facts indicate that the relative importance of cardiovascular diseases (CVD) risk factors may have changed. Although it was confirmed at an individual level that the degree of obesity was positively associated with CVD incidence, there is a sizeable proportion of individuals who are at an increased CVD risk state without being overweight/obese in today's Japan. Thus, further implementation and promotion of activities are needed to bring about meaningful changes in the obesity trend in communities that are harmonized with other domains of CVD prevention activities.

Obesity and weight gain are associated with increased risk of coronary heart disease in Western countries. However, their impact is not well elucidated in Asia, where body mass index (BMI) levels are generally lower than in Western countries. We examined associations of BMI (kg/m2) and weight change with risk of coronary heart disease in Japanese people. A total of 43 235 men and 47 444 women aged 40–69 years living in communities were followed up from 1990 to 2001 in the Japan Public Health Center-based (JPHC) prospective study . During 879 619 person-years of follow-up, we documented 399 cases of coronary heart disease (334 myocardial infarction and 65 sudden cardiac death) for men and 119 (95 myocardial infarction and 24 sudden cardiac death) for women. Compared with persons with BMI 23.0–24.9, men, but not women, with BMI ⩾30.0 had higher risk of coronary heart disease and myocardial infarction; the multivariable relative risks for men were 1.8 (1.1–3.0) and 1.9 (1.1–3.2), respectively. When weight change was examined according to BMI at age 20 years, men with initial BMI

To examine the relationship between systemic immune status and carotid atherosclerosis in elderly men, differential leukocyte counts and lymphocyte subpopulations were measured in 557 apparently healthy Japanese men aged 60-75 years. Each individual also underwent high-resolution ultrasonography for measurement of intima-media thickness (IMT) of the common carotid arteries. The increased numbers of circulating lymphocyte subpopulations, including memory T cells (CD4+CD45RO+T cells) and late-phase activated B cells (CD19+CD80+B cells) correlated significantly and positively with the mean IMT of the common carotid artery after adjustment for age, smoking, and other cardiovascular risk factors. The positive associations of CD19+CD80+B and CD4+CD45RO+ T cell counts with mean IMT were more evident among nonsmokers, hypertensives, and men with lower HDL-cholesterol levels. The present epidemiological study provided the evidence that alterations in lymphocyte subpopulations, in particular memory T cells and late-phase activated B cells concur with carotid atherosclerosis among free-living elderly men.