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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 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.

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

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 and purpose An effect of dietary carotenes on risk of cardiovascular disease (CVD) is uncertain. We aimed to investigate whether the association between dietary carotenes intake and risk of CVD mortality will persist after controlling for the intakes of potential cardioprotective dietary factors that correlate with dietary alpha- and/or beta-carotenes. Methods and results We followed up a total of 58,646 Japanese between 1988 and 1990 and 2009. We used a food frequency questionnaire (FFQ) to determine the dietary intakes of carotenes, and estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality in relation to carotene intake by the proportional hazard regression developed by David Cox. During 965,970 person-years of follow-up (median 19.3 years), we identified 3388 total CVD deaths. After adjusting for demographic and lifestyle factors, dietary intakes of alpha-carotene were significantly associated with the reduced risk of mortality from coronary heart disease (CHD); adjusted HR (95% CI) in the highest versus lowest quintiles of intake was 0.75 (0.58–0.96; P-trend = 0.02) and dietary intakes of beta-carotene were significantly associated with the reduced risk of mortality from CVD, CHD, and other CVD; adjusted HRs (95% CIs) were 0.88 (0.79–0.98; P-trend = 0.04), 0.78 (0.61–0.99; P-trend = 0.01), and 0.81 (0.67–0.98; P-trend = 0.04), respectively. However, after further adjusting for the dietary intakes of potassium, calcium, vitamins C, E, or K, these associations disappeared. Conclusions —Dietary alpha- and beta-carotene intakes were not associated with risk of CVD mortality after controlling for intakes of other potential cardioprotective nutrients.

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

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.

Although a positive link between hypertension and intraocular pressure (IOP) has been suggested, the individual effects of systolic and diastolic blood pressure (SBP and DBP, respectively) on IOP remain unclear, particularly among Japanese populations. Here, we conducted a large-scale, cross-sectional study to determine individual and combined effects of SBP/DBP and hypertension on IOP. In total, 6783 Japanese people aged over 40 years underwent systemic and ophthalmological examinations, including measurements of blood pressure and IOP, conducted using non-contact tonometers. After adjusting for a priori known confounding factors, SBP and DBP levels were found to be positively correlated with IOP levels. The multivariable-adjusted odds ratio when comparing the hypertensive and normotensive groups for the prevalence of ocular hypertension was 1.88 (95% confidence interval, 1.14–3.08). When analysing the combined effects of SBP and DBP on ocular hypertension, SBP elevation had a greater effect on ocular hypertension than DBP increase. In conclusion, SBP and DBP levels and the prevalence of systemic hypertension were found to be positively associated with IOP levels and the prevalence of ocular hypertension in an ophthalmologically healthy Japanese population. Our findings suggest that systemic blood pressure control may be key for controlling IOP.

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0·603 (0·400-1·00) standard drinks per day, and the NDE varied between 0·002 (0-0) and 1·75 (0·698-4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0-0·403) to 1·87 (0·500-3·30) standard drinks per day and an NDE that ranged between 0·193 (0-0·900) and 6·94 (3·40-8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3-65·4) were aged 15-39 years and 76·9% (73·0-81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Research reported in this publication was supported by the Bill & Melinda Gates Foundation. S Afzal acknowledges the support for intellectual contributions to this manuscript by the Department of Community Medicine and Epidemiology at King Edward Medical University, Lahore, Pakistan. T Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. L Belo acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. D Bennett is supported by the UK Medical Research Council Population Health Research Unit at the University of Oxford (Oxford, UK). M Carvalho acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. L Castro-de-Araujo was funded by the Medical Research Council (UK), Grant no. MR/T03355X/1 and by the National Institute of Mental Health Grant no. R01MH128911. FJ Elgar is supported by the Canada Research Chairs program. F Greaves acknowledges support from the NIHR Applied Research Collaboration for NW London. V K Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. VB Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. C Herteliu is partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is partially supported by a grant from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported by the Operational Programme Research, Development and Education –Project, Postdoc2MUNI “(No. CZ.02.2.69/0.0/0.0/18_053/0016952). S M S Islam is funded by the National Health and Medical Research Council and received funding from the National Heart Foundation of Australia. The Serbian part of this GBD-related contribution has been co-financed through Grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. M Kivimaki was supported by the Wellcome Trust (221854/Z/20/Z), the UK Medical Research Council (MR/S011676/1), the US National Institute on Aging (R01AG056477), and the Academy of Finland (350426). K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. B Lacey acknowledges support from the UK Biobank, funded largely by the UK Medical Research Council and Wellcome. S Lorkowski acknowledges institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig (Germany; German Federal Ministry of Education and Research; grant agreement number 01EA1808A). G Lucchetti received a productivity scholarship from the Brazilian National Council for Scientific and Technological Development — CNPq (Level 1D). J McGrath was supported by the Danish National Research Foundation (Niels Bohr Professor). J McGrath is employed by the Queensland Centre for Mental Health Research (Australia), which receives support from the Queensland Health Department. C Parry acknowleges the South African Medical Research Council. A Peden is supported by a National Health and Medical Research Council Emerging Leadership Fellowship (Grant ID: APP2009306). M R Phillips was supported in part by the Global Alliance for Chronic Diseases - National Natural Science Foundation of China (NSFC. No. 81761128031). M Pinheiro acknowledges FCT for funding through program DL 57/2016 – Norma transitória. A Rahman acknowledges the support from the Data Science Research Unit in Charles Sturt University (Bathurst, NSW, Australia). U Saeed would like to acknowledge the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges support from Ain Shams University (Cairo, Egypt) and the Egyptian Fulbright Mission Program. N Senthil Kumar acknowledges the DBT, New Delhi sponsored Advanced State Level Biotech Hub (BT/NER/143/SP44475/2021), Mizoram University (Aizawl, Mizoram, India) for facilitating this work. F Sha is supported by the Shenzhen Science and Technology Program (Grant No. KQTD20190929172835662). A Shetty acknowledges Kasturba Medical College (Mangalore, India) and Manipal Academy of Higher Education (Manipal, India) for all the academic support. R Shrestha acknowledges a career development award from the National Institutes of Health (K01DA051346). D Silva was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)-Finance Code 001 and is supported in part by CNPq - Brazil (309589/2021-5). D Sleet acknowledges partial support from Veritas Management Group, Inc and The Bizzell Group, LLC. S Trias-Llimós acknowledges research funding from the Juan de la Cierva-Formación program of the Spanish Ministry of Science and Innovation (FJC-2019-039314-I). Sí

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.

Supplemental Digital Content is available in the text., Background and Purpose: The effect of green tea and coffee consumption on mortality among cardiovascular diseases survivors is unknown. We examined the association between green tea and coffee consumption and mortality among persons with and without stroke or myocardial infarction (MI). Methods: In the Japan Collaborative Cohort Study, 46 213 participants (478 stroke survivors, 1214 MI survivors, and 44 521 persons without a history of stroke or MI), aged 40 to 79 years at baseline (1988–1990), completed a lifestyle, diet, and medical history questionnaire and were followed up regarding mortality until 2009. The Cox proportional hazard model was used to calculate the multivariable hazard ratios with 95% CIs of all-cause mortality after adjusting for potential confounding factors. Results: During the 18.5-year median follow-up period, 9253 cases were documented. Green tea consumption was inversely associated with all-cause mortality among stroke or MI survivors; the multivariable hazard ratios (95% CIs) for stroke survivors were 0.73 (0.42–1.27) for 1 to 6 cups/wk, 0.65 (0.36–1.15) for 1 to 2 cups/d, 0.56 (0.34–0.92) for 3 to 4 cups/d, 0.52 (0.31–0.86) for 5 to 6 cups/d, and 0.38 (0.20–0.71) for ≥7 cups/d, compared with nondrinkers. A similar inverse association was observed for MI survivors, but not evident for those without a history of stroke or MI. Coffee consumption was inversely associated with all-cause mortality in persons without a history of stroke or MI; the multivariable hazard ratios (95% CIs) were 0.86 (0.82–0.91) for 1 to 6 cups/wk, 0.86 (0.80–0.92) for 1 cup/d, and 0.82 (0.77–0.89) for ≥2 cups/d, compared with nondrinkers. The corresponding hazard ratios (95% CIs) for MI survivors were 0.69 (0.53–0.91), 0.78 (0.55–1.10), and 0.61 (0.41–0.90). No such association was observed for stroke survivors. Conclusions: Green tea consumption can be beneficial in improving the prognosis for stroke or MI survivors, whereas coffee consumption can also be so for persons without a history of stroke or MI as well as MI survivors.

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.

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.

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.

Although the association between fruit consumption and CHD risk has been well studied, few studies have focused on flavonoid-rich fruits (FRF), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87 177 men and women aged 44–75 years who were free of CVD and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a FFQ. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13·2 years, we identified 1156 incident CHD cases. After full adjustment for covariates including demographics, lifestyles and dietary factors, the HR were 0·93 (95 % CI 0·77, 1·11), 0·91 (95 % CI 0·75, 1·11), 0·84 (95 % CI 0·67, 1·04) and 0·78 (95 % CI 0·62, 0·99) for the second, third, fourth and fifth quintiles compared with the lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRF, in particular, citrus fruits, may be associated with a lower risk of developing CHD.

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.

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.

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.

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.

The prospective association between secondhand smoke (SHS) and the risk of incident cardiovascular disease (CVD) remains unclear. This study was the first to examine the association between SHS and risks of ischemic heart disease (IHD), stroke, and total CVD in a large cohort in Asia. The study followed 24,232 never-smoking women aged 40-59 from around Japan (Akita, Iwate, Nagano, Niigata, Ibaraki, Kochi, Nagasaki, and Okinawa prefectures). Their husbands were classified into never, former, and current smokers. After adjustment for age, body mass index, alcohol consumption, histories of hypertension and diabetes mellitus, medication use for hyperlipidemia, menopausal status, and public health center areas, the hazard ratios (HRs) of CVD according to husbands' smoking status were estimated by Cox proportional hazards models. During the 440,360 person-years follow-up, 846 women had total CVDs (103 IHDs, 744 strokes). The proportional hazard assumption was not assured during the total follow-up from 1990 to 2012, but so was then the follow-up ofand ≥ 10 person-years were examined separately. The multivariable HRs (95% confidence intervals) associated with husbands' current versus non-current smoking was 2.02 (1.19-3.45) for IHD, 1.18 (0.98-1.42) for stroke, and 1.25 (1.05-1.49) for total CVD in the follow-up of ≥10 person-years. The SHS from husbands may raise the risk of IHD among middle-aged never-smoking women.

We evaluated the association between total soy, soy product (natto, miso and tofu) and isoflavone intake and incident disabling dementia in a Japanese population.We conducted a population-based prospective study in 18,991 men and 22,456 women. Intake of soy products and isoflavone was calculated using a validated food frequency questionnaire when participants were 45-74 years old (1995 and 1998). Incident disabling dementia was defined by the daily living disability status related to dementia in the long-term care insurance program of Japan from 2006 to 2016. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of disabling dementia were calculated by quintiles of total soy, individual soy product and isoflavone intake, using Cox proportional hazard regression models.Total soy product intake was not associated with disabling dementia risk in both men and women. By individual soy products, natto intake was marginally inversely associated with disabling dementia in women (trend P = 0.050). When we stratified by age, this inverse association was clearer in women aged under 60 years (multivariate HR for the highest versus lowest quintile was 0.78, 95% CI 0.59-1.04, trend P = 0.020 for those aged under 60 years and 0.90, 95% CI 0.77-1.05, trend P = 0.23 for those aged 60 years and older, respectively). Any soy product or isoflavone intake was not associated with disabling dementia risk in men.Although total soy product intake was not associated with disabling dementia risk, natto intake may contribute to reducing the risk of disabling dementia in women, especially in those aged under 60 years.

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.

Several studies have shown that smoking is a significant risk factor for pneumonia, but it is uncertain to what extent smoking cessation reduces the risk. This study aimed to investigate whether and to what extent smoking cessation is associated with reduced risk of mortality from pneumonia in a Japanese, prospective, community-based cohort. We examined 94,972 individuals (mean age, 57 years; women, 57%) who provided valid responses to a lifestyle questionnaire including questions about smoking. We used years of smoking cessation at baseline to divide former smokers into 5 groups: 0-1 year, 2-4 years, 5-9 years, 10-14 years, and 15 years or more. The endpoint was the underlying cause of death from pneumonia. During the median 19-year follow-up of 94,972 study participants, 1806 died from pneumonia. Multivariable hazard ratios (95% confidence intervals) compared with the current smokers were 1.02 (0.72-1.45) for 0-1 year of smoking cessation at baseline, 0.92 (0.70-1.22) for 2-4 years, 0.95 (0.74-1.21) for 5-9 years, 0.71 (0.53-0.96) for 10-14 years, 0.63 (0.48-0.83) for 15 years or more, and 0.50 (0.36-0.70) for never-smokers. Although smoking increases the risk of pneumonia mortality, the present study showed that the risk of pneumonia mortality decreased with years of smoking cessation, eventually improving to levels similar to those of non-smokers for 10 years or more. Continued smoking cessation may be effective in preventing pneumonia deaths.

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.

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

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.

Aims: The frequency of breakfast intake has been reported to be inversely associated with the risk of cardiovascular events; however, it is uncertain what the impact of the energy and nutrient intakes from breakfast are. We assessed the association between these intakes from breakfast and the risk of stroke prospectively. Methods: In a baseline survey of four Japanese communities between 1981 and 1990, we enrolled 3 248 residents (1 662 men and 1 586 women) aged 40–59 years who were free from stroke and heart disease and who responded to the 24-hour dietary recall survey. We assessed the dietary intake at breakfast, lunch, dinner, and other times separately. Results: During the median 25-year follow-up, 230 individuals (147 men and 83 women) developed stroke. After adjustment for age, community, other dietary intakes, and lifestyle and physiological factors, the multivariable-adjusted hazard ratios (95% confidence intervals) of intracerebral hemorrhage for the highest versus lowest quartiles of energy intake from breakfast were 0.38 (0.15–0.99) in men and 1.36 (0.36–5.10) in women. For the major nutrients, a higher saturated or monounsaturated fat intake at breakfast was associated with a reduced risk of intracerebral hemorrhage in men, and remained statistically significant after further adjustment for intake of other major nutrients from breakfast. Conclusions: A higher intake of energy from breakfast, primarily saturated or monounsaturated fat, was associated with a reduced risk of intracerebral hemorrhage in Japanese men.

In Japan, heart disease and cerebrovascular disease were the second and fourth leading cause of death, respectively in 2014. Hematocrit, the ratio of the red blood cells to the total volume of blood is known to play a role in cardiovascular diseases. However, the relationship between elevated hematocrit and the risk of cardiovascular disease based on sex has not been examined in Asian countries. We analyzed data from the Ibaraki Prefectural Health Study, a community-based large cohort study, which included 87,533 individuals, aged 40 to 79 years living in 38 municipalities of the Ibaraki Prefecture, who had completed an annual health checkup in 1993, and were followed until 2013. The hematocrit levels of the subjects were categorized into 5 quintiles (Q1-Q5), and hazard ratios for cause-specific mortality were calculated using the Cox proportional hazards regression models. Age and other cardiovascular risk factors were the covariates in the study. During the follow-up for a mean of 17.9 years, 1,207 deaths (615 men and 592 women) due to acute myocardial infarction (AMI) were reported in this population. The p values for the trend in the Q3-Q5 groups were 0.661 for men and 0.020 for women. Additionally, these values were significant in younger (40 to 59 years) women but not in older (60 to 79 years) women. This study is the first one to demonstrate an association between high hematocrit level and risk of AMI mortality in younger Japanese women, but not in men and older women.

Using Food Frequency Questionnaires (FFQs) to compare dietary references for screening has been in high demand. However, FFQs have been widely used for ranking individuals in a population based on their dietary intake. We determined the validity of sodium (salt equivalent) intake, potassium intake, and sodium-to-potassium (Na/K) ratio obtained using the FFQ for identifying individuals who deviated from the dietary reference intakes (DRIs) measured using multiple 24-h urinary excretion measurements or 12-day weighed food records (WFR). This study included 235 middle-aged subjects. The correlation coefficients (CCs) between the FFQ and WFR estimates were mostly moderate (0.24–0.54); the CCs between the FFQ and 24-h urinary excretion measurements were low or moderate (0.26–0.38). Values of area under the receiver-operating curve (AUC) at the point of DRIs for salt equivalent or potassium were >0.7 with the WFR as the reference standard and 0.60–0.76 with the 24-h urinary excretion as the reference standard. Using both standard measures, the AUC for the Na/K ratio was

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.

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).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 (1Y), 1 through 5 years (1-5Y), and 6 or more years ago (6Y+).Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the untreated,1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H. pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive.A significant reduction in H. pylori antibody titer occurs within 1 year after eradication treatment, but that a long period is needed to achieve complete negative conversion.

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.

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. For complete list of authors see http://dx.doi.org/10.1016/S2468-2667(21)00065-7

The associations of daily total physical activity and total moderate to vigorous physical activity (MVPA) with dementia are still unclear.To investigate the association between daily total physical activity and subsequent risk of disabling dementia in large-scale, extended follow-up prospective study.This prospective cohort study used data from questionnaires collected between 2000 and 2003 from 8 areas from the Japan Public Health Center-based Prospective Disabling Dementia Study. Participants included adults aged 50 to 79 years in with available follow-up data on disabling dementia. Data analysis was performed from February 1, 2019, to July 31, 2021.Daily total physical activity, total MVPA, and leisure-time MVPA.The main outcome was incidence of disabling dementia during the dementia ascertainment period between 2006 and 2016, based on the national long-term care insurance system. Risks of dementia in association with daily total physical activity, total MVPA, and leisure time MVPA were calculated using multivariable adjusted hazard ratios (aHRs).Among 43 896 participants (mean [SD] age, 61.0 [7.5] years; 23 659 [53.9%] women), 5010 participants were newly diagnosed with disabling dementia during a mean (SD) of 9.5 (2.8) years in the dementia ascertainment period. In the highest daily total physical activity group, compared with the lowest activity group, risk of dementia was lower in men (aHR, 0.75 [95% CI, 0.66-0.85]; P for trend .001) and women (aHR, 0.75 [95% CI, 0.67-0.84]; P for trend .001). Similar inverse associations were observed in men and women for total MVPA (men: aHR, 0.74 [95% CI, 0.65-0.84]; P for trend .001; women: aHR, 0.74 [95% CI, 0.66-0.83]; P for trend .001) and leisure-time MVPA (men: aHR, 0.59 [95% CI, 0.53-0.67]; P for trend .001; women: aHR, 0.70 [95% CI, 0.63-0.78]; P for trend .001). However, these inverse associations disappeared when participants diagnosed with disabling dementia within 7 years of the starting point were excluded in men (aHR, 0.93 [95%CI, 0.77-1.12]) and within 8 years were excluded in women (aHR, 0.86 [95%CI, 0.71-1.04]). The association remained significant among men in the highest vs lowest group of leisure-time MVPA, after excluding participants diagnosed within the first 9 years (aHR, 0.72 [95% CI, 0.56-0.92]; P for trend = .004).This cohort study examined associations of daily total physical activity and total MVPA with risk of disabling dementia. The findings suggest that a high level of leisure-time MVPA was associated with decreased risk of disabling dementia in men.

Publisher's version (útgefin grein), Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need., The work of the co-ordinating centre was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/ 002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The Emerging Risk Factor Collaboration’s website https://www.phpc.cam.ac.uk/ceu/erfc/list-of-studies/ has compiled a list provided by investigators of some of the funders of the component studies in this analysis. I.W. was supported by the Medical Research Council Unit Programme MC_UU_12023/21. M.K. is supported by the Netherlands Organization for Scientific Research (NWO) Veni grant (Veni, 91616079). J.P. is supported by Erasmus Mundus Western Balkans (ERAWEB), a project funded by the European Commission.

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

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

Aim: Seaweed is a popular traditional foodstuff in Asian countries. To our knowledge, few studies have examined the association of seaweed intake with mortality from cardiovascular disease. We examined the association of frequency of seaweed intake with total and specific cardiovascular disease mortality. Methods: We examined the association of seaweed intake with mortality from cardiovascular disease among 40,234 men and 55,981 women who participated in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Sex-specific hazard ratios for mortality from cardiovascular disease (stroke, stroke subtypes, and coronary heart disease) according to the frequency of seaweed intake were calculated stratified by study area and adjusted for potential cardiovascular risk factors and dietary factors. Results: During the 1,580,996 person-year follow-up, 6,525 cardiovascular deaths occurred, of which 2,820 were due to stroke, and 1,378, to coronary heart disease. Among men, the multivariable analysis showed that participants who ate seaweed almost every day compared with those who never ate seaweed had hazard ratios (95% confidence interval; P for trend) of 0.79 (0.62–1.01; 0.72) for total cardiovascular disease, 0.70 (0.49–0.99; 0.47) for total stroke, 0.69 (0.41–1.16; 0.11) for cerebral infarction. Among women, the multivariable-adjusted hazard ratios were 0.72 (0.55–0.95; 0.001) for total cardiovascular disease, 0.70 (0.46–1.06; 0.01) for total stroke, and 0.49 (0.27–0.90; 0.22) for cerebral infarction. No associations were observed between seaweed intake and risk of intraparenchymal hemorrhage and coronary heart disease among either men or women. Conclusions: We found an inverse association between seaweed intake and cardiovascular mortality among Japanese men and women, especially that from cerebral infarction.