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1. Development and Validation of a Risk Prediction Model for Atherosclerotic Cardiovascular Disease in Japanese Adults: The Hisayama Study

Author: Takanori Honda, Satoko Sakata, Mao Shibata, Yoshihiko Furuta, Yoichiro Hirakawa, Toshiharu Ninomiya, Sanmei Chen, Daigo Yoshida, Takanari Kitazono, and Jun Hata
Subjects: Adult, Male, medicine.medical_specialty, Specific risk, Blood Pressure, Disease, 030204 cardiovascular system & hematology, Overfitting, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Prospective Studies, Exercise, Proteinuria, Proportional hazards model, Atherosclerotic cardiovascular disease, business.industry, Biochemistry (medical), Middle Aged, Atherosclerosis, medicine.disease, Blood pressure, Cardiovascular Diseases, Cardiology, Female, Morbidity, medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Follow-Up Studies, Forecasting
Abstract: Aim To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods A total of 2,454 participants aged 40-84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell's C statistics, a calibration plot with the Greenwood-Nam-D'Agostino test, and a bootstrap validation procedure. Results During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell's C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D'Agostino test: P=0.29 for the multivariable model, 0.52 for the simplified score). Conclusion We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.
Published: 2022
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2. Diabetes Mellitus, Elevated Hemoglobin A1c, and Glycated Albumin Are Associated with the Presence of All-Cause Dementia and Alzheimer’s Disease: The JPSC-AD Study

Author: Moeko, Noguchi-Shinohara, Sohshi, Yuki-Nozaki, Chiemi, Abe, Ayaka, Mori, Mai, Horimoto, Masami, Yokogawa, Natsuko, Ishida, Yukio, Suga, Junko, Ishizaki, Mai, Ishimiya, Hiroyuki, Nakamura, Kiyonobu, Komai, Mao, Shibata, Tomoyuki, Ohara, Jun, Hata, Toshiharu, Ninomiya, and Masahito, Yamada
Subjects: Blood Glucose, Glycation End Products, Advanced, Male, medicine.medical_specialty, endocrine system diseases, Gastroenterology, Prediabetic State, Insulin resistance, Japan, Alzheimer Disease, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Dementia, Glycated Serum Albumin, Prospective Studies, Prediabetes, Risk factor, Vascular dementia, Serum Albumin, Aged, Glycemic, Glycated Hemoglobin, business.industry, General Neuroscience, General Medicine, Odds ratio, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Logistic Models, Hyperglycemia, Multivariate Analysis, Female, Insulin Resistance, Geriatrics and Gerontology, business
Abstract: Background: Glucose dysmetabolism is an important risk factor for dementia. Objective: We investigated the associations of diabetes mellitus, the levels of glycemic measures, and insulin resistance and secretion measures with dementia and its subtypes in a cross-sectional study. Methods: In this study, 10,214 community-dwelling participants were enrolled. Hemoglobin A1c (HbA1c), the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), the HOMA of percent β-cell function (HOMA-β), and the glycated albumin (GA) was evaluated. The associations of each measure with Alzheimer’s disease (AD) and vascular dementia (VaD) were investigated. Results: The multivariable-adjusted odds ratios (ORs) of AD were significantly higher in participants with diabetes mellitus than in those without diabetes (1.46 [95% CI: 1.08–1.97]). Higher HbA1c levels were significantly associated with AD at diabetes (≥6.5%) and even at prediabetes (5.7 %–6.4 %) levels; multivariable-adjusted ORs for AD in participants at the diabetes level were 1.72 (95% CI: 1.19–2.49), and those in participants at the prediabetes level were 1.30 (95% CI: 1.00–1.68), compared with those in normal participants. Moreover, higher GA levels were associated with AD. No associations were observed between the diabetic status or the levels of glycemic measures and VaD. In addition, no significant relationships were observed between insulin resistance and secretion measurements and AD and VaD. Conclusion: Our findings indicate that diabetes mellitus and hyperglycemia are significantly associated with AD, even in individuals at the prediabetes level.
Published: 2022
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3. Pathologic Diabetic Nephropathy in Autopsied Diabetic Cases With Normoalbuminuria From a Japanese Community-Based Study

Author: Yoichiro Hirakawa, Yoshinao Oda, Jun Hata, Takanari Kitazono, T. Sasaki, Toshiharu Ninomiya, Nobuo Tsuboi, Toshiaki Nakano, Mao Shibata, Kaneyasu Nakagawa, and Takashi Yokoo
Subjects: medicine.medical_specialty, business.industry, Urinary system, diabetic nephropathy, medicine.disease, Community based study, Gastroenterology, albuminuria, community-based study, Diabetic nephropathy, morphologic study, Health examination, autopsy, Nephrology, Clinical Research, Internal medicine, Diabetes mellitus, medicine, Albuminuria, medicine.symptom, business, Normal range
Abstract: Introduction Albuminuria is a clinical hallmark of diabetic nephropathy (DN). Nevertheless, it is controversial whether pathologic DN lesions exist in individuals with diabetes with normoalbuminuria. We investigated the association between albuminuria levels and the frequency of DN lesions in autopsied diabetic cases from a Japanese community. Methods A total of 106 autopsied cases with diabetes mellitus (mean age = 76 years, 43.4% male) who died within 6 years after their last health examination were included in the study. Urinary albumin-creatinine ratio (UACR) levels were divided into the following 3 groups, Graphical abstract
Published: 2021

4. Serum NT-proBNP levels and histopathological myocardial fibrosis in autopsied cases from a Japanese community: The Hisayama Study

Author: Toshiharu Ninomiya, Kensuke Izumaru, Takuya Nagata, Jun Hata, Emi Oishi, Nobuo Tsuboi, Takaya Sasaki, Satoko Sakata, Takashi Yokoo, Yoshinao Oda, and Takanari Kitazono
Subjects: Male, medicine.medical_specialty, Heart disease, medicine.drug_class, Cardiac fibrosis, Autopsy, 030204 cardiovascular system & hematology, Elevated serum, 03 medical and health sciences, 0302 clinical medicine, Japan, Internal medicine, Natriuretic Peptide, Brain, Natriuretic peptide, medicine, Humans, 030212 general & internal medicine, Aged, 80 and over, business.industry, Repeated measures design, Prognosis, medicine.disease, Fibrosis, Peptide Fragments, Confidence interval, Cardiology, Myocardial fibrosis, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: natriuretic peptide is associated with myocardial fibrosis in animal models and among patients with heart disease. However, it remains unclear whether serum N-terminal pro-B-type peptide (NT-proBNP) levels are associated with histopathologically proven myocardial fibrosis among individuals without apparent heart disease. This study aimed to evaluate the association between serum NT-proBNP levels and the histopathologically estimated myocardial fibrotic area in autopsied samples from a community.we selected 63 cases without apparent heart disease with available data of serum NT-proBNP concentrations within six years before death (average age: 82 years; male: 52%) from autopsied cases in a community, and evaluated the percentage areas of myocardial fibrosis in four cardiac segments from each case (i.e. 252 cardiac segments in total). The association between serum NT-proBNP levels and the percentage area of myocardial fibrosis was estimated using a linear mixed model for repeated measures.serum NT-proBNP levels were positively correlated with myocardial fibrotic area [Pearson's correlation coefficient: r = 0.49 (95% confidence interval: 0.28-0.66), p 0.001]. Serum NT-proBNP levels were significantly associated with the percentage areas of myocardial fibrosis after adjusting for potential confounding factors. There was no evidence of heterogeneity in the association between the subgroups with and without reduced estimated glomerular filtration rate (60 mL/min/1.73 mthe present study demonstrated that elevated serum NT-proBNP levels were associated with the histopathologically measured myocardial fibrotic area in autopsied cases from a community. These findings may help clarify the association between elevated serum NT-proBNP levels and myocardial fibrosis and their influence on prognosis.
Published: 2021
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5. Serum High-Sensitivity C-Reactive Protein Levels and the Development of Atrial Fibrillation in a General Japanese Population ― The Hisayama Study ―

Author: Takanari Kitazono, Toshiharu Ninomiya, Satoko Sakata, Takuya Nagata, Tomoko Yoshikawa, Yoichiro Hirakawa, Yoshitaka Hirooka, Hiroyuki Tsutsui, and Jun Hata
Subjects: Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Internal medicine, Atrial Fibrillation, medicine, Humans, 030212 general & internal medicine, Risk factor, Aged, Proportional Hazards Models, biology, business.industry, Proportional hazards model, C-reactive protein, Confounding, Hazard ratio, Atrial fibrillation, General Medicine, medicine.disease, Confidence interval, C-Reactive Protein, biology.protein, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Cohort study
Abstract: BACKGROUND Atrial fibrillation (AF) is a common arrhythmia in the elderly, and causes complications such as cardioembolic stroke. Serum high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, has been reported to be a risk factor for developing AF in Western countries. However, few community-based studies have examined this issue in general Asian populations.Methods and Results:A total of 2,510 community-dwelling Japanese participants aged ≥40 years without a history of AF were divided into 4 groups according to the sex-specific quartiles of serum hs-CRP concentrations (Q1, lowest and Q4, highest) and followed up for 24 years. The hazard ratios and their 95% confidence intervals for the development of AF were estimated using a Cox proportional hazards model. During the follow up, 234 subjects developed AF. The risk of AF increased significantly with elevating serum hs-CRP levels after adjustment for potential confounding factors (hazard ratio [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.26 [0.83-1.92]; Q3, 1.77 [1.18-2.66]; and Q4, 1.89 [1.24-2.86]; P for trend
Published: 2021
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6. Prevalence and Mortality of Sarcopenia in a Community-dwelling Older Japanese Population: The Hisayama Study

Author: Yoichiro Hirakawa, Kimitaka Nakamura, Mao Shibata, Jun Hata, Hiro Kishimoto, Yoshihiko Furuta, Yasuharu Nakashima, Toshiharu Ninomiya, Tomoyuki Ohara, Takanari Kitazono, Daigo Yoshida, and Takanori Honda
Subjects: Male, Medicine (General), medicine.medical_specialty, Activities of daily living, Epidemiology, prevalence, 030209 endocrinology & metabolism, Logistic regression, sarcopenia, 03 medical and health sciences, R5-920, 0302 clinical medicine, Japan, medicine, Humans, Clinical Epidemiology, 030212 general & internal medicine, Aged, Proportional Hazards Models, Aged, 80 and over, Proportional hazards model, business.industry, Public health, Hazard ratio, General Medicine, Japanese population, musculoskeletal system, medicine.disease, mortality, Confidence interval, body regions, asian working group for sarcopenia, Sarcopenia, Female, Original Article, Independent Living, business, human activities, Demography
Abstract: Background: The prevalence of sarcopenia defined using the Asian Working Group for Sarcopenia (AWGS) criteria in Asian communities has not been fully addressed. Moreover, few studies have addressed the influence of sarcopenia on mortality. Methods: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined using the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model. Results: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (P = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both P for trend
Published: 2021
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7. Comparison of the contributions of impaired beta cell function and insulin resistance to the development of type 2 diabetes in a Japanese community: the Hisayama Study

Author: Udai Nakamura, Toshiharu Ninomiya, Naoko Mukai, Masahito Yoshinari, Yoichiro Hirakawa, Mayu Higashioka, Jun Hata, Takanari Kitazono, Daigo Yoshida, and Takanori Honda
Subjects: 0301 basic medicine, medicine.medical_specialty, education.field_of_study, Proportional hazards model, business.industry, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, Type 2 diabetes, medicine.disease, Obesity, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Prediabetes, business, Prospective cohort study, education
Abstract: Our aim was to compare the contributions of impaired beta cell function (IBF) and insulin resistance with the development of type 2 diabetes in a Japanese community. A total of 2094 residents aged 40–79 years without diabetes underwent a health examination including a 75 g OGTT in 2007. Participants were divided into four groups according to the presence or absence of IBF (insulinogenic index/HOMA-IR ≤28.5) and insulin resistance (HOMA-IR ≥1.61) and were followed up for 7 years (2007–2014). Cox’s proportional hazards model was used to estimate HRs and 95% CIs for type 2 diabetes. The population attributable fractions (PAFs) due to IBF, insulin resistance, and their combination were calculated. At baseline, the prevalence of isolated IBF, isolated insulin resistance, and both IBF and insulin resistance were 5.4%, 24.1% and 9.5%, respectively. During the follow-up period, 272 participants developed type 2 diabetes. The multivariable-adjusted HRs (95% CI) and PAFs (95% CI) for type 2 diabetes were 6.3 (4.3, 9.2) and 13.3% (8.7, 17.7) in the participants with isolated IBF, 1.9 (1.3, 2.7) and 10.5% (4.0, 16.6) in those with isolated insulin resistance, and 8.0 (5.7, 11.4) and 29.3% (23.0, 35.1) in those with both IBF and insulin resistance, respectively, compared with the participants without either. The present study suggests that the combination of IBF and insulin resistance makes the main contribution to the development of type 2 diabetes in Japanese communities.
Published: 2021
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8. N-Terminal Pro–B-Type Natriuretic Peptide and Incident CKD

Author: T. Sasaki, Nobuo Tsuboi, Yoshihiko Furuta, Takanori Honda, Daigo Yoshida, Toshiharu Ninomiya, Jun Hata, Satoko Sakata, Takuya Nagata, Takashi Yokoo, Sanmei Chen, Emi Oishi, and Takanari Kitazono
Subjects: renal impairment, medicine.medical_specialty, kidney dysfunction, medicine.drug_class, 030232 urology & nephrology, Renal function, community-based cohort study, 030204 cardiovascular system & hematology, lcsh:RC870-923, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, medicine, Natriuretic peptide, Proteinuria, natriuretic peptide, business.industry, Japanese population, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, female genital diseases and pregnancy complications, Confidence interval, Nephrology, Biomarker (medicine), N terminal pro b type natriuretic peptide, proteinuria, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract: Introduction Serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels have been associated with the progression of kidney impairment among patients with chronic kidney disease (CKD), but only a few studies have investigated the association between serum NT-proBNP levels and incident CKD in general populations. Methods A total of 2486 Japanese community-dwelling residents ≥40 years of age without CKD at baseline were followed up by repeated annual health examinations for 10 years. Participants were divided into 4 groups according to serum NT-proBNP levels. CKD was defined as an estimated glomerular filtration rate (eGFR), Graphical abstract
Published: 2021
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9. The Association of Small Dense Low-Density Lipoprotein Cholesterol and Coronary Heart Disease in Subjects at High Cardiovascular Risk

Author: Jun Hata, Mao Shibata, Takanori Honda, Haruhiko Osawa, Daigo Yoshida, Takanari Kitazono, Kenichi Goto, Toshiharu Ninomiya, Satoko Sakata, and Mayu Higashioka
Subjects: Male, medicine.medical_specialty, Coronary Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, Prospective Studies, Prospective study, Prospective cohort study, Risk assessment, Aged, High-risk population, business.industry, Proportional hazards model, Cholesterol, Biochemistry (medical), Hazard ratio, Cholesterol, LDL, Middle Aged, medicine.disease, Confidence interval, Coronary heart disease, chemistry, Heart Disease Risk Factors, Cardiology, Original Article, Female, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Small dense LDL cholesterol, Biomarkers, Kidney disease, Lipoprotein
Abstract: Aim The present study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in subjects at high cardiovascular risk. Methods A total of 3,080 participants without prior cardiovascular disease (CVD), aged ≥ 40 years, were followed up for a median of 8.3 years, which were divided into two groups, those with serum sdLDL cholesterol levels of ＜35 mg/dL or ≥ 35 mg/dL. Then, subjects were stratified by the status of diabetes, CVD-related comorbidities (defined as the presence of diabetes, chronic kidney disease, or peripheral artery disease), and the CVD risk assessment according to the Japan Atherosclerosis Society Guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using a Cox proportional hazards model. Results During the follow-up, 79 subjects developed CHD. The risk for incident CHD was higher in subjects with serum sdLDL cholesterol of ≥ 35 mg/dL than those with sdLDL cholesterol of ＜35 mg/dL (HR 2.09, 95%CI 1.26-3.45) after adjusting for traditional risk factors. In the subgroup analyses, the multivariable-adjusted HR for incident CHD increased significantly in those with serum sdLDL cholesterol of ≥ 35 mg/dL among subjects with diabetes (HR 2.76, 95%CI 1.09-7.01), subjects with CVD-related comorbidities (HR 2.60, 95%CI 1.21-5.58), and high-risk category defined as the presence of CVD-related comorbidities or a Suita score of ≥ 56 points (HR 1.93, 95%CI 1.02-3.65). Conclusions Elevated serum sdLDL cholesterol was associated with the development of CHD even in subjects at high cardiovascular risk.
Published: 2021

10. Emotional Loneliness Is Associated With a Risk of Dementia in a General Japanese Older Population: The Hisayama Study

Author: Toshiharu Ninomiya, Takuya Nagata, Jun Hata, Yukiko Morisaki, Masako Hosoi, Nobuyuki Sudo, Taro Nakazawa, Akane Mihara, Emi Oishi, Daigo Yoshida, Naoki Hirabayashi, Tomoyuki Ohara, Kozo Anno, and Mao Shibata
Subjects: Male, Aging, medicine.medical_specialty, Social Psychology, Emotions, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Epidemiology, medicine, Humans, Dementia, 030212 general & internal medicine, Social isolation, Prospective cohort study, Depression (differential diagnoses), Aged, Proportional Hazards Models, Aged, 80 and over, Proportional hazards model, Incidence, Loneliness, Hazard ratio, medicine.disease, Clinical Psychology, Social Isolation, Female, Geriatrics and Gerontology, medicine.symptom, Psychology, Gerontology, 030217 neurology & neurosurgery, Follow-Up Studies, Clinical psychology
Abstract: Objectives To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. Method A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales—namely, social and emotional loneliness—by using the 6-item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. Results During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08–2.40) and 1.65 (1.07–2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. Discussion The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.
Published: 2020
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11. Association between serum glycated albumin and risk of cardiovascular disease in a Japanese community: The Hisayama Study

Author: Takanori Honda, Satoko Sakata, Toshiharu Ninomiya, Tomoyuki Ohara, Tomohiro Nakao, Akane Mihara, Sanmei Chen, Jun Hata, Emi Oishi, Takanari Kitazono, and Yoichiro Hirakawa
Subjects: Glycation End Products, Advanced, 0301 basic medicine, medicine.medical_specialty, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Internal medicine, Diabetes mellitus, Epidemiology, medicine, Humans, Glycated Serum Albumin, Cumulative incidence, Prospective Studies, cardiovascular diseases, Prospective cohort study, Stroke, Serum Albumin, Proportional Hazards Models, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, Confidence interval, 030104 developmental biology, Cardiovascular Diseases, Cardiology and Cardiovascular Medicine, business
Abstract: We aimed to investigate the association of serum glycated albumin (GA) levels with the risk of cardiovascular disease (CVD) and its subtypes, including coronary heart disease (CHD) and stroke, in a general Japanese population.A total of 2965 Japanese community-dwellers aged ≥40 years were followed prospectively for a median of 10.2 years (2002-2012). Serum GA was measured by the enzymatic method and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum GA levels on CVD risk.During the follow-up, 213 subjects developed CVD; 95 had CHD, and 133 had stroke. The cumulative incidence of CVD, CHD, and stroke increased significantly with increasing serum GA levels (all p for trend0.02). Compared with the lowest serum GA quartile (13.6%), the multivariable-adjusted HRs (95% CI) of the highest quartile (≥15.7%) were 2.33 (1.46-3.68) for CVD, 2.23 (1.11-4.50) for CHD, and 2.47 (1.38-4.40) for stroke. In addition, a subgroup analysis showed that CVD risk increased significantly with increasing levels of serum GA in both subjects with and without diabetes mellitus. The increasing trend of CVD risk for higher serum GA levels was also observed in subjects with low hemoglobin AOur findings suggest that higher serum GA levels are significantly associated with the development of CVD and its subtypes, even among subjects without diabetes or those with normal hemoglobin A
Published: 2020
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12. Association of glucose tolerance status with pancreatic β‐ and α‐cell mass in community‐based autopsy samples of Japanese individuals: The Hisayama Study

Author: Hiroshi Itoh, Yoshinao Oda, Yuusuke Watanabe, Yoichiro Hirakawa, Naoko Mukai, Daigo Yoshida, Jun Inaishi, Jun Hata, Yoshifumi Saisho, and Toshiharu Ninomiya
Subjects: Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Autopsy, 030204 cardiovascular system & hematology, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, Prediabetic State, 03 medical and health sciences, 0302 clinical medicine, Japan, Internal medicine, Diabetes mellitus, Insulin-Secreting Cells, Glucose Intolerance, Internal Medicine, medicine, Humans, Prediabetes, Glycemic, Aged, Community based, Type 2 diabetes mellitus, business.industry, β‐Cell mass, Type 2 Diabetes Mellitus, General Medicine, Articles, Japanese population, medicine.disease, Prognosis, RC648-665, Cross-Sectional Studies, Clinical Science and Care, Diabetes Mellitus, Type 2, Glucagon-Secreting Cells, Female, Original Article, business, Biomarkers, Cell mass, Follow-Up Studies
Abstract: Aims/Introduction Changes in histologically quantified β‐ and α‐cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β‐ and α‐cell mass according to the glucose tolerance status. Materials and Methods Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75‐g oral glucose tolerance test within 5 years before death were selected from 643 community‐based autopsy samples collected from 2002 to 2016. Fractional β‐cell area (BCA) and α‐cell area were quantified with Image Pro Plus software. Associations of BCA and α‐cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman’s correlation coefficients between glycemic markers and β‐cell function were estimated. Results The mean values of BCA decreased significantly with worsening glucose tolerance status (mean ± standard error 1.85 ± 0.10% in normal glucose tolerance, 1.59 ± 0.11% in prediabetes and 1.17 ± 0.11% in type 2 diabetes mellitus, P for trend, A lower fractional β‐cell area was associated significantly with the deterioration of glucose tolerance status in community‐based autopsy samples of Japanese individuals.
Published: 2020

13. Recent status of self-measured home blood pressure in the Japanese general population: a modern database on self-measured home blood pressure (MDAS)

Author: Takashi Hisamatsu, Toshiharu Ninomiya, Mai Kabayama, Takayoshi Ohkubo, Katsuyuki Miura, Jun Hata, Kei Kamide, Yasuharu Tabara, Masahiro Kikuya, Satoko Sakata, Kayo Godai, Kei Asayama, Yukako Tatsumi, and Emi Oishi
Subjects: medicine.medical_specialty, Evening, Physiology, medicine.drug_class, Population, Diastole, Blood Pressure, 030204 cardiovascular system & hematology, computer.software_genre, Sitting, 03 medical and health sciences, 0302 clinical medicine, Asian People, Heart Rate, Reference Values, Epidemiology, Internal Medicine, medicine, Humans, Registries, 030212 general & internal medicine, Antihypertensive drug, education, Morning, education.field_of_study, Database, business.industry, Blood Pressure Determination, Circadian Rhythm, Self Care, Blood pressure, Cardiology and Cardiovascular Medicine, business, computer
Abstract: Despite the clinical usefulness of self-measured home blood pressure (BP), reports on the characteristics of home BP have not been sufficient and have varied due to the measurement conditions in each study. We constructed a database on self-measured home BP, which included five Japanese general populations as subdivided aggregate data that were clustered and meta-analyzed according to sex, age category, and antihypertensive drug treatment at baseline (treated and untreated). The self-measured home BPs were collected after a few minutes of rest in a sitting position: (1) the morning home BP was measured within 1 h of waking, after urination, before breakfast, and before taking antihypertensive medication (if any); and (2) the evening home BP was measured just before going to bed. The pulse rate was simultaneously measured. Eligible data from 2000 onward were obtained. The morning BP was significantly higher in treated participants than in untreated people of the same age category, and the BP difference was more marked in women. Among untreated residents, home systolic/diastolic BPs measured in the morning were higher than those measured in the evening; the differences were 5.7/5.0 mmHg in women (ranges across the cohorts, 5.3-6.8/4.7-5.4 mmHg) and 7.3/7.7 mmHg in men (ranges, 6.4-8.5/7.0-8.7 mmHg). In contrast, the home pulse rate in women and men was 2.4 (range, 1.5-3.7) and 5.6 (range, 4.6-6.6) beats per minute, respectively, higher in the evening than in the morning. We demonstrated the current status of home BP and home pulse rate in relation to sex, age, and antihypertensive treatment status in the Japanese general population. The approach by which fine-clustered aggregate statistics were collected and integrated could address practical issues raised in epidemiological research settings.
Published: 2020
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14. Serum homocysteine and risk of dementia in Japan

Author: Mao Shibata, Emi Oishi, Daigo Yoshida, Yoichiro Hirakawa, Tomoyuki Ohara, Takanari Kitazono, Takanori Honda, Satoko Sakata, Jun Hata, Yoshihiko Furuta, Toshiharu Ninomiya, and Sanmei Chen
Subjects: medicine.medical_specialty, Hyperhomocysteinemia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Japan, Alzheimer Disease, Risk Factors, Polymorphism (computer science), Internal medicine, medicine, Genetic predisposition, Humans, Dementia, Genetic Predisposition to Disease, Prospective Studies, Vascular dementia, Homocysteine, Methylenetetrahydrofolate Reductase (NADPH2), Aged, Proportional Hazards Models, Aged, 80 and over, biology, business.industry, Proportional hazards model, Dementia, Vascular, Serum homocysteine, Middle Aged, Neuropsychiatry, medicine.disease, Psychiatry and Mental health, Methylenetetrahydrofolate reductase, Risk allele, biology.protein, 030211 gastroenterology & hepatology, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: ObjectiveTo examine the association between serum total homocysteine levels (tHcy) and dementia risk.MethodsA total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia.ResultsDuring the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer’s disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51–3.43) for all-cause dementia, 1.96 (1.19–3.24) for AD and 2.51 (1.14–5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8–15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07).ConclusionHigh serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.
Published: 2020
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15. Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort

Author: Yoichiro Hirakawa, Yoshihiko Furuta, Jun Hata, Atsushi Shimizu, Takanari Kitazono, Toshiharu Ninomiya, Tsuyoshi Hachiya, and Daigo Yoshida
Subjects: Adult, Male, Multifactorial Inheritance, medicine.medical_specialty, Diabetic Cardiomyopathies, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Risk Assessment, Genome, Brain Ischemia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Internal medicine, Genotype, Humans, Medicine, Prospective Studies, Prospective cohort study, Aged, 030304 developmental biology, Aged, 80 and over, Advanced and Specialized Nursing, 0303 health sciences, Molecular epidemiology, business.industry, Smoking, Middle Aged, Stroke, Case-Control Studies, Hypertension, Ischemic stroke, Female, Polygenic risk score, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, Genome-Wide Association Study
Abstract: Background and Purpose— Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods— A total of 3038 subjects aged ≥40 years were followed up for 10 years (2002–2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results— During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels ( P for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16–5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors ( P for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04–2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions— A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.
Published: 2020
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16. Elevated serum glycated albumin and glycated albumin : hemoglobin A1cratio were associated with hippocampal atrophy in a general elderly population of Japanese: The Hisayama Study

Author: Jun Hata, Tomoyuki Ohara, Daigo Yoshida, Takanari Kitazono, Naoki Hirabayashi, Yoshihiko Furuta, Yoichiro Hirakawa, Toshiharu Ninomiya, Takanori Honda, and Mao Shibata
Subjects: Glycation End Products, Advanced, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Hippocampus, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Magnetic resonance imaging, 0302 clinical medicine, Japan, Internal medicine, Diabetes mellitus, Global brain atrophy, Risk factors in epidemiology, Internal Medicine, medicine, Humans, Dementia, Glycated Serum Albumin, Longitudinal Studies, Geriatric Assessment, Serum Albumin, Aged, Glycemic, Glycated Hemoglobin, Analysis of Variance, business.industry, Brain, Articles, Organ Size, General Medicine, RC648-665, medicine.disease, Clinical Science and Care, Blood pressure, Endocrinology, Brain size, Original Article, Female, Hemoglobin, Atrophy, business, Body mass index, 030217 neurology & neurosurgery
Abstract: Aims/Introduction To investigate the association of alternative glycemic measures – namely, serum glycated albumin (GA), hemoglobin A1c (HbA1c) and the GA : HbA1c ratio – with global brain and hippocampal atrophy in a general elderly Japanese population. Materials and Methods A total of 1,278 Japanese individuals aged ≥65 years in a community participated in brain magnetic resonance imaging scanning and screening examination of health status in 2012. We measured total brain volume (TBV), hippocampal volume (HV) and intracranial volume (ICV) using the data from the magnetic resonance imaging examination. The association of each glycemic measure with the ratios of TBV : ICV (an indicator of global brain atrophy) and HV : ICV (an indicator of hippocampal atrophy) was examined by analysis of covariance. Results The mean values of the TBV : ICV and HV : ICV ratios decreased significantly with elevating serum GA levels and GA : HbA1c ratio levels (all P for trend, Higher levels of serum glycated albumin and the glycated albumin : hemoglobin A1c ratio, but not hemoglobin A1c, were significantly associated with global brain and hippocampal atrophy. These significant associations were still observed in the sensitivity analysis after excluding individuals with dementia and mild cognitive impairment. Glycemic variability might be closely associated with the risk of global brain and hippocampus atrophy.
Published: 2020
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17. Ratios of serum eicosapentaenoic acid to arachidonic acid and docosahexaenoic acid to arachidonic acid were inversely associated with serum resistin levels: The Hisayama Study

Author: Toshiharu Ninomiya, Daigo Yoshida, Takanori Honda, Mayu Higashioka, Takanari Kitazono, Haruhiko Osawa, Jun Hata, Ryoichi Kawamura, Yasunori Takata, and Yoichiro Hirakawa
Subjects: Male, medicine.medical_specialty, Docosahexaenoic Acids, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Cross‐sectional study, Asian People, Japan, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Resistin, education, Aged, chemistry.chemical_classification, education.field_of_study, Arachidonic Acid, business.industry, General Medicine, Articles, Middle Aged, medicine.disease, RC648-665, Eicosapentaenoic acid, Endocrinology, Cross-Sectional Studies, Clinical Science and Care, chemistry, Eicosapentaenoic Acid, Docosahexaenoic acid, Cardiovascular Diseases, Multivariate Analysis, Arachidonic acid, Female, Original Article, business, Polyunsaturated fatty acid, n−3 polyunsaturated fatty acids
Abstract: Aims/Introduction Resistin is an adipocyte‐derived polypeptide that leads to the progression of insulin resistance and subsequent atherosclerosis. Some studies have reported an association between self‐reported intake of n−3 polyunsaturated fatty acids (PUFAs) and serum resistin levels. However, no studies have investigated the association between the ratio of serum levels of n−3 to serum n−6 PUFAs and the serum resistin concentration in the general population. Materials and Methods We carried out a cross‐sectional study of 3,200 community‐dwelling Japanese individuals aged ≥40 years in 2002–2003. The ratios of serum eicosapentaenoic acid or docosahexaenoic acid to arachidonic acid (AA) were categorized into quartiles. The associations of serum eicosapentaenoic acid/AA and docosahexaenoic acid/AA with the serum resistin concentration were assessed using linear regression models with adjustment for potential confounding factors. Results The geometric mean of serum resistin was 10.3 ng/mL. The age‐ and sex‐adjusted geometric mean of serum resistin decreased significantly with increased levels of serum eicosapentaenoic acid/AA (quartile 1: 11.3 ng/mL; quartile 2: 10.6 ng/mL; quartile 3: 10.3 ng/mL; quartile 4: 9.3 ng/mL; P for trend, Resistin is a polypeptide that leads to the progression of insulin resistance and inflammation. The present study showed the inverse association of the ratios of serum eicosapentaenoic acid to arachidonic acid, docosahexaenoic acid to arachidonic acid, and serum resistin levels in a general population. Higher intakes of eicosapentaenoic acid and docosahexaenoic acid would lower serum resistin levels.
Published: 2020

18. Serum uric acid levels and cardiovascular mortality in a general Japanese population: the Hisayama Study

Author: Mao Shibata, Daigo Yoshida, Toshiharu Ninomiya, Takanori Honda, Satoko Sakata, Takanari Kitazono, Kenichi Goto, Yoichiro Hirakawa, Jun Hata, and Emi Oishi
Subjects: Male, medicine.medical_specialty, Physiology, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Japan, Risk Factors, Internal medicine, Epidemiology, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Stroke, Aged, Proportional hazards model, business.industry, Hazard ratio, Confounding, Absolute risk reduction, Middle Aged, medicine.disease, Uric Acid, Survival Rate, chemistry, Cardiovascular Diseases, Cardiology, Uric acid, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Studies on the association between serum uric acid levels and the risk of cardiovascular disease have yielded inconsistent results. We investigated the association of serum uric acid levels with cardiovascular disease mortality in a Japanese community. A total of 2633 community-dwelling Japanese people aged ≥40 years without a history of cardiovascular disease were followed up for 19 years. Serum uric acid levels were categorized into quintiles (Q1, lowest; Q5, highest). The hazard ratios for mortality from cardiovascular disease, stroke, and coronary heart disease were computed using a Cox proportional hazards model. During the follow-up, 235 subjects died from cardiovascular disease (including 84 from stroke and 53 from coronary heart disease). Risks for cardiovascular disease mortality were higher in both the Q1 and Q5 groups than in the Q3 group after adjustment for confounding factors (Q1, hazard ratio 1.50 [95% confidence interval 0.94-2.39]; Q2, 1.06 [0.66-1.72]; Q3, 1.00 [reference]; Q4, 1.44 [0.93-2.23]; and Q5, 1.89 [1.23-2.91]). A similar U-shaped association was observed for stroke mortality (Q1, 3.26 [1.29-8.25]; Q2, 2.21 [0.85-5.73]; Q3, 1.00 [reference]; Q4, 2.65 [1.07-6.58]; and Q5, 3.77 [1.54-9.24]), while coronary heart disease mortality was increased only in the Q5 group (Q1, 1.27 [0.46-3.50]; Q2, 0.85 [0.29-2.48]; Q3, 1.00 [reference]; Q4, 1.57 [0.63-3.92]; and Q5, 2.53 [1.03-6.18]). Elevated serum uric acid was suggested to be a significant risk factor for stroke or coronary heart disease mortality in a Japanese community. Conversely, the excess risk of stroke mortality in individuals with lower serum uric acid levels may indicate a possible cerebroprotective role of uric acid.
Published: 2020
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19. Anticoagulation and Risk of Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source Having No Potential Source of Embolism

Author: Tetsuro Ago, Ryu Matsuo, Yoshinobu Wakisaka, Jun Hata, Fumi Kiyuna, Masahiro Kamouchi, Noriko Sato, Takanari Kitazono, and Kuniyuki Nakamura
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Administration, Oral, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Japan, Recurrence, Risk Factors, Internal medicine, Secondary Prevention, Humans, Medicine, In patient, Registries, Aged, Aged, 80 and over, Embolic Stroke, business.industry, Proportional hazards model, Anticoagulant, Confounding, Hazard ratio, Anticoagulants, Middle Aged, medicine.disease, Embolic stroke, Treatment Outcome, Neurology, Embolism, Cardiology, Female, Observational study, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract: Background: This study aimed to determine whether use of oral anticoagulants (OACs) was associated with a reduced risk of recurrent stroke compared with use of antiplatelets (APs) in patients with embolic stroke of undetermined source (ESUS) having no potential source of embolism. Methods: Of 8,790 patients with acute ischemic stroke registered at 7 centers in the Fukuoka Stroke Registry from June 2007 to May 2017, we included 681 patients (mean age 69.7 [SD 14.1] years, 48.3% men) who experienced ESUS without a potential source of embolism and received OAC alone or AP alone. We estimated hazard ratios (HRs) and 95% confidential intervals (CIs) of recurrent ischemic stroke or any stroke after discharge using a Cox proportional hazards model and Fine and Gray model. Results: During a mean follow-up of 3.4 (SD 1.7) years, event rates of recurrent ischemic stroke were 4.4 per 100 person-years in 489 patients treated with AP and 2.0 per 100 person-years in 192 patients treated with OAC. OAC use was associated with a reduced risk of recurrent ischemic stroke, even after adjusting for potential confounding factors (multivariable-adjusted HR [95% CI], 0.42 [0.23–0.80]) and when additionally considering death as a competing risk (0.45 [0.24–0.85]). The reduced risk of recurrent ischemic stroke was still observed in patients treated with OAC (0.32 [0.15–0.67]) in reference to propensity score-matched patients treated with AP. These associations were maintained for all types of stroke, including ischemic and hemorrhagic stroke. Conclusions: This nonrandomized observational study suggests that anticoagulation therapy might be associated with a reduced risk of recurrent stroke compared with antiplatelet therapy in patients with ESUS in whom no potential source of embolism was identified. Further study should be performed in consideration of a potential source of embolism even in patients with ESUS.
Published: 2020
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20. Decline in Handgrip Strength From Midlife to Late-Life is Associated With Dementia in a Japanese Community: The Hisayama Study

Author: Takanori Honda, Tomoyuki Ohara, Daigo Yoshida, Yozo Hatabe, Shigenobu Kanba, Emi Oishi, Takanari Kitazono, Toshiharu Ninomiya, Jun Hata, and Mao Shibata
Subjects: Male, Longitudinal study, medicine.medical_specialty, Aging, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Epidemiology, medicine, Dementia, Humans, 030212 general & internal medicine, Longitudinal Studies, Vascular dementia, Aged, handgrip strength, lcsh:R5-920, Hand Strength, business.industry, Proportional hazards model, Incidence (epidemiology), Confounding, longitudinal study, alzheimer’s disease, General Medicine, Middle Aged, medicine.disease, Confidence interval, Original Article, Female, epidemiology, business, lcsh:Medicine (General), Neurology and Psychiatry, Demography, dementia
Abstract: Background: The association between decline in handgrip strength from midlife to late life and dementia is unclear. Methods: Japanese community-dwellers without dementia aged 60 to 79 years (ie, individuals in late life; mean age, 68 years) were followed for 24 years (1988–2012) (n = 1,055); 835 of them had participated in a health examination in 1973–1974 (mean age, 53 years), and these earlier data were used for the midlife analysis. Using a Cox proportional hazards model, we estimated the risk conferred by a decline in handgrip strength over a 15-year period (1973–74 to 1988) from midlife to late life on the development of total dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) over the late-life follow-up period from 1988 to 2012. Results: During the follow-up, 368 subjects experienced total dementia. The age- and sex-adjusted incidence of total dementia increased significantly with greater decline in handgrip strength (increased or unchanged handgrip strength [≥+0%] 25.1, mildly decreased [−14 to −1%] 28.4, and severely decreased [≤−15%] 38.9 per 1,000 person-years). A greater decline in handgrip strength was significantly associated with higher risk of total dementia after adjusting for potential confounding factors; subjects with severely decreased handgrip strength had 1.51-fold (95% confidence interval, 1.14–1.99, P < 0.01) increased risk of total dementia compared to those with increased or unchanged handgrip strength. Similar significant findings were observed for AD, but not for VaD. Conclusions: Our findings suggest that a greater decline in handgrip strength from midlife to late life is an important indicator for late-life onset of dementia.
Published: 2020

21. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. Santos, Marjeta Majer, Herman Schargrodsky, Bruna Gonçalves Cordeiro da Silva, Ebrahim Eftekhar, Jesús Vioque, Marisa K. Sophiea, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Stefan Söderberg, Isabel O. Oliveira, Joanne Katz, Xingwang Ye, Christophe Tzourio, Marie Zins, Aneta Weres, Ulrich Keil, Haiquan Xu, Akihiro Yoshihara, Rachel Dankner, Gabriella Gruden, Maroje Sorić, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Christa L. Lilly, Veikko Salomaa, Gilad Twig, Senthil K Vasan, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Wilma M. Hopman, Karl-Heinz Jöckel, Ari Voutilainen, Peter Schnohr, Jerzy Chudek, Katia Vergetti Bloch, Vincenzo Capuano, Jyh Eiin Wong, Torben Jørgensen, Anja Schienkiewitz, Nader Saki, Carolina Tarqui-Mamani, Maria Cecília Formoso Assunção, Kazi M. Jamil, Juraci Almeida Cesar, Pedro J Ortiz, Delphine De Smedt, Luciana Zaccagni, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Romana Roccaldo, Sara Magnacca, Peter Stehle, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Tabara Yasuharu, Ali Ghanbari, Gyulli M. Kazakbaeva, Takuro Furusawa, Felicia Cañete, Kari Kuulasmaa, Justina Vaitkeviciute, (NCD-RisC), NCD Risk Factor Collaboration, Imperial College London, Harvard T.H. Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH 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, Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen 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, Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , 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Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng , Luxia Zhang , Zhen-Yu Zhang , Dong Zhao , Ming-Hui Zhao , Wenhua Zhao , Shiqi Zhen , Wei Zheng , Yingfeng Zheng , Bekbolat Zholdin , Maigeng Zhou , Dan Zhu , Marie Zins , Emanuel Zitt , Yanina Zocalo , Julio Zuñiga Cisneros , Monika Zuziak , Majid Ezzati , Sarah Filippi, Epidemiology, Iurilli, Maria LC, Zhou, Bin, Bennett, James E, Carrillo-Larco, Rodrigo M, Sophiea, Marisa K, Rodriguez-Martinez, Andrea, Bixby, Honor, Solomon, Bethlehem D, Taddei, Cristina, Danaei, Goodarz, Di Cesare, Mariachiara, Stevens, Gretchen A, Riley, Leanne M, Savin, Stefan, Cowan, Melanie J, Bovet, Pascal, Damasceno, Albertino, Chirita-Emandi, Adela, Hayes, Alison J, Ikeda, Nayu, Jackson, Rod T, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Saidi, Olfa, Sebert, Sylvain, Sorić, Maroje, Starc, Gregor, Gregg, Edward W, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, 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Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021
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22. Day-by-Day Blood Pressure Variability in the Subacute Stage of Ischemic Stroke and Long-Term Recurrence

Author: Kenji Fukuda, Ryu Matsuo, Masahiro Kamouchi, Fumi Kiyuna, Noriko Sato, Kuniyuki Nakamura, Jun Hata, Yoshinobu Wakisaka, Tetsuro Ago, Tsutomu Imaizumi, Hisashi Kai, Takanari Kitazono, Takao Ishitsuka, Setsuro Ibayashi, Kenji Kusuda, Kenichiro Fujii, Tetsuhiko Nagao, Yasushi Okada, Masahiro Yasaka, Hiroaki Ooboshi, Katsumi Irie, Tsuyoshi Omae, Kazunori Toyoda, Hiroshi Nakane, Hiroshi Sugimori, Shuji Arakawa, Jiro Kitayama, Shigeru Fujimoto, Shoji Arihiro, Junya Kuroda, Yoshihisa Fukushima, Yasuhiro Kumai, and Noriko Makihara
Subjects: Male, medicine.medical_specialty, Time Factors, Blood Pressure, Brain Ischemia, Recurrence, Internal medicine, medicine, Humans, Prospective Studies, Stage (cooking), Mortality, Acute ischemic stroke, Stroke, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Aged, 80 and over, business.industry, Blood Pressure Determination, Middle Aged, medicine.disease, Blood pressure, Ischemic stroke, Cardiology, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Background and Purpose: This study aimed to determine whether variability of day-by-day blood pressure (BP) during the subacute stage of acute ischemic stroke is predictive of long-term stroke recurrence. Methods: We analyzed 7665 patients (mean±SD age: 72.9±13.1 years; women: 42.4%) hospitalized for first-ever ischemic stroke in 7 stroke centers in Fukuoka, Japan, from June 2007 to November 2018. BP was measured daily during the subacute stage (4–10 days after onset). Its mean and coefficient of variation (CV) values were calculated and divided into 4 groups according to the quartiles of these BP parameters. Patients were prospectively followed up for recurrent stroke or all-cause death. The cumulative event rate was calculated with the Kaplan-Meier method. We estimated the hazard ratios and 95% confidence intervals of the events of interest after adjusting for potential confounders and mean BP values using Cox proportional hazards models. The Fine-Gray model was also used to account for the competing risk of death. Results: With a mean (±SD) follow-up duration of 3.9±3.2 years, the rates of recurrent stroke and all-cause death were 3.9 and 9.9 per 100 patient-years, respectively. The cumulative event rates of recurrent stroke and all-cause death increased with increasing CVs of systolic BP and diastolic BP. The systolic BP CV was significantly associated with an increased risk of recurrent stroke after adjusting for multiple confounders and mean BP (hazard ratio [95% CI] for fourth quartile versus first quartile, 1.26 [1.05–1.50]); the risk of recurrent stroke also increased with an increasing systolic BP CV for nonfatal strokes (1.26 [1.05–1.51]) and when death was regarded as a competing risk (1.21 [1.02–1.45]). Similar associations were observed for the diastolic BP CV. Conclusions: Day-by-day variability of BP during the subacute stage of acute ischemic stroke was associated with an increased long-term risk of recurrent stroke.
Published: 2021

23. Serum elaidic acid concentration and risk of dementia

Author: Mao Shibata, Ryuji Toh, Takanori Honda, Ken-ichi Hirata, Satoko Sakata, Masakazu Shinohara, Takanari Kitazono, Toshiharu Ninomiya, Jun Hata, Daigo Yoshida, Yasuhiro Irino, Tatsuro Ishida, Yoichiro Hirakawa, Shigenobu Kanba, Kazuhiro Uchida, and Tomoyuki Ohara
Subjects: Male, medicine.medical_specialty, Trans fat, Oleic Acids, Gastroenterology, Gas Chromatography-Mass Spectrometry, chemistry.chemical_compound, Japan, Alzheimer Disease, Interquartile range, Internal medicine, medicine, Humans, Dementia, Risk factor, Vascular dementia, Aged, Proportional Hazards Models, Aged, 80 and over, chemistry.chemical_classification, business.industry, Dementia, Vascular, Incidence, Middle Aged, Trans Fatty Acids, medicine.disease, Elaidic acid, chemistry, Female, Neurology (clinical), Alzheimer's disease, business, Polyunsaturated fatty acid
Abstract: ObjectiveThe associations between trans fatty acids and dementia have been unclear. We investigated the prospective association between serum elaidic acid (trans 18:1 n-9) levels, as an objective biomarker for industrial trans fat, and incident dementia and its subtypes.MethodsIn total, 1,628 Japanese community residents aged 60 and older without dementia were followed prospectively from when they underwent a screening examination in 2002–2003 to November 2012 (median 10.3 years, interquartile range 7.2–10.4 years). Serum elaidic acid levels were measured using gas chromatography/mass spectrometry and divided into quartiles. The Cox proportional hazards model was used to estimate the hazard ratios for all-cause dementia, Alzheimer disease (AD), and vascular dementia by serum elaidic acid levels.ResultsDuring the follow-up, 377 participants developed some type of dementia (247 AD, 102 vascular dementia). Higher serum elaidic acid levels were significantly associated with greater risk of developing all-cause dementia (p for trend = 0.003) and AD (p for trend = 0.02) after adjustment for traditional risk factors. These associations remained significant after adjustment for dietary factors, including total energy intake and intakes of saturated and polyunsaturated fatty acids (both p for trend ConclusionsThe findings suggest that higher serum elaidic acid is a possible risk factor for the development of all-cause dementia and AD in later life. Public health policy to reduce industrially produced trans fatty acids may assist in the primary prevention of dementia.
Published: 2019
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24. Association between Axial Length and Myopic Maculopathy

Author: Toshiharu Ninomiya, Jun Hata, Miho Yasuda, Yoichiro Hirakawa, Emi Ueda, Koh Hei Sonoda, Sawako Hashimoto, and Kohta Fujiwara
Subjects: medicine.medical_specialty, Visual acuity, genetic structures, Cross-sectional study, Population, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, medicine, Cutoff, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Odds ratio, Macular degeneration, medicine.disease, eye diseases, Confidence interval, 030221 ophthalmology & optometry, Maculopathy, sense organs, medicine.symptom, business
Abstract: Purpose To assess the association between axial length (AL) and the prevalence of myopic maculopathy in a general Japanese population. Design Population-based cross-sectional study. Participants A total of 2790 Hisayama residents 40 years of age or older who consented to participate and had available data of AL and fundus photographs for the right eyes were enrolled in this study. Methods Myopic maculopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, or macular degeneration. The optimal cutoff values of axial length for identifying myopic maculopathy were estimated from the receiver operating characteristic curve. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a logistic regression analysis. Main Outcome Measures Odds ratios of AL for prevalent myopic maculopathy and the optimal cutoff values of AL for detecting myopic maculopathy. Results Longer AL was associated significantly with prevalence of myopic maculopathy in both genders. The optimal cutoff values of AL for identifying myopic maculopathy were 25.9 mm in men and 25.3 mm in women. Participants with ALs of these values or longer showed a significantly higher OR for myopic maculopathy than those with AL of less than these values (men: OR, 21.23; 95% CI, 8.74–51.57; women: OR, 38.49; 95% CI, 18.03–86.49). Conclusions The present study found that there was a positive association between AL and the likelihood of myopic maculopathy, and the cutoff levels of AL for identifying myopic maculopathy were 25.9 mm in men and 25.3 mm in women. Our findings suggest that patients with AL close to or longer than these values should undergo intensive treatment and detailed ophthalmic follow-up.
Published: 2019
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25. Long-term regular exercise and intraocular pressure: the Hisayama Study

Author: Koh Hei Sonoda, Toshiharu Ninomiya, Jun Hata, Daigo Yoshida, Kohta Fujiwara, Takeshi Yoshitomi, Sawako Hashimoto, Hiro Kishimoto, and Miho Yasuda
Subjects: Adult, Male, 0301 basic medicine, Intraocular pressure, medicine.medical_specialty, Time Factors, Waist, Urban Population, genetic structures, Blood Pressure, Comorbidity, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Japan, Regular exercise, Diabetes mellitus, Internal medicine, medicine, Humans, Exercise, Intraocular Pressure, Retrospective Studies, business.industry, Incidence, Confounding, Glaucoma, Middle Aged, medicine.disease, eye diseases, Sensory Systems, Ophthalmology, 030104 developmental biology, Blood pressure, Cardiovascular Diseases, 030221 ophthalmology & optometry, Cardiology, Female, sense organs, business, Body mass index, Follow-Up Studies, Cohort study
Abstract: To investigate the association between long-term regular exercise (exercise frequency and exercise time) and 5-year changes in intraocular pressure in a general Japanese population.This population-based, cohort study was conducted in 2007. A total of 3119 Japanese community dwellers aged ≥ 40 years underwent eye examinations including intraocular pressure measurement with a noncontact tonometer. Of these, 1871 subjects (801 men and 1070 women) who underwent intraocular pressure measurement in 2012 participated. We assessed the associations of exercise frequency and exercise time with intraocular pressure using a linear regression model, adjusted for age and possible risk factors that can affect intraocular pressure.The mean 5-year intraocular pressure change ± standard deviation was - 0.84 ± 1.9 mmHg. After adjustment for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habit, alcohol intake, work intensity levels, and intraocular pressure at baseline, we observed that increased exercise frequency (times/week) and increased exercise time (min/week) were both significantly associated with reduced intraocular pressure (p 0.05 each). In the subgroup analyses based on the presence/absence of possible confounding risk factors, there was no evidence of heterogeneity among all subgroups (p for heterogeneity 0.2).Increased exercise frequency levels and increased exercise time are both independently associated with reduced intraocular pressure levels after adjustment for confounding factors.
Published: 2019
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26. Association Between Serum β-Alanine and Risk of Dementia

Author: Toshiharu Ninomiya, Takanari Kitazono, Tomoyuki Ohara, Shuntaro Yamashita, Yoichiro Hirakawa, Mao Shibata, Daigo Yoshida, Takanori Honda, Satoko Sakata, Kuniyoshi Shimizu, Jun Hata, Satoru Kuhara, and Yoshinori Katakura
Subjects: medicine.medical_specialty, Epidemiology, Population, 030204 cardiovascular system & hematology, Prevention of dementia, 03 medical and health sciences, 0302 clinical medicine, Blood serum, Japan, Alzheimer Disease, Risk Factors, Internal medicine, Humans, Medicine, Dementia, Prospective Studies, Vascular dementia, education, Aged, Proportional Hazards Models, education.field_of_study, business.industry, Dementia, Vascular, Incidence, Hazard ratio, Middle Aged, medicine.disease, Quartile, beta-Alanine, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract: We examined the association between serum concentrations of β-alanine, a metabolite of carnosine and anserine, and the risk of dementia in a general population of elderly Japanese persons. In 2007, 1,475 residents of Hisayama, Japan, aged 60–79 years and without dementia were divided into 4 groups according to quartiles of serum β-alanine concentrations (quartile 1, lowest; quartile 4, highest) and followed for a median of 5.3 years. During follow-up, 117 subjects developed all-cause dementia (Alzheimer in 77 cases and vascular dementia in 31). The risk of all-cause dementia decreased with increasing serum β-alanine levels after adjustment for potential confounding factors (quartile 2, hazard ratio (HR) = 0.73 (95% confidence interval (CI): 0.45, 1.18); quartile 3, HR = 0.50 (95% CI: 0.28, 0.89); quartile 4, HR = 0.50 (95% CI: 0.27, 0.92); P = 0.01 for trend). A similar inverse association was observed for Alzheimer disease (quartile 2, HR = 0.78 (95% CI: 0.44, 1.38); quartile 3, HR = 0.53 (95% CI: 0.26, 1.06); quartile 4, HR = 0.53 (95% CI: 0.25, 1.10); P = 0.04 for trend) but not for vascular dementia. We found that higher serum β-alanine levels were significantly associated with lower risks of all-cause dementia and Alzheimer disease. Because serum β-alanine levels reflect intakes of carnosine/anserine, higher intakes of carnosine/anserine might be beneficial for the prevention of dementia.
Published: 2019
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27. Serum Ethylamine Levels as an Indicator of <scp>l</scp>-Theanine Consumption and the Risk of Type 2 Diabetes in a General Japanese Population: The Hisayama Study

Author: Susumu Takemoto, Jun Hata, Takanori Honda, Shozo Nishimoto, Yoichiro Hirakawa, Toshiharu Ninomiya, Takanori Teramoto, Masahito Yoshinari, Mao Shibata, Takanari Kitazono, Satoko Sakata, Daigo Yoshida, Mayu Higashioka, and Noriyuki Kanzaki
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Drinking Behavior, 030209 endocrinology & metabolism, Type 2 diabetes, Lower risk, Prediabetic State, Eating, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Glutamates, Japan, Risk Factors, Diabetes mellitus, Internal medicine, Ethylamines, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Prediabetes, Aged, Advanced and Specialized Nursing, Tea, business.industry, Incidence, Middle Aged, medicine.disease, Obesity, Endocrinology, Diabetes Mellitus, Type 2, Quartile, chemistry, Female, Insulin Resistance, Ethylamine, business, Biomarkers
Abstract: OBJECTIVE This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS A total of 2,253 community-dwelling Japanese individuals aged 40–79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87–2.10, 2.11–5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of l-theanine–rich green tea products containing 8 mg of l-theanine by 12 healthy volunteers. RESULTS During follow-up, 282 subjects developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine (P for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariable-adjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49–0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was >5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h. CONCLUSIONS Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of l-theanine consumption.
Published: 2019
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28. Association Between Genetic Risk and Development of Type 2 Diabetes in a General Japanese Population: The Hisayama Study

Author: Toshiharu Ninomiya, Jun Inaishi, Yoichiro Kamatani, Yoichiro Hirakawa, Yukihide Momozawa, Momoko Horikoshi, Naoko Mukai, Masato Akiyama, Mayu Higashioka, Michiaki Kubo, Masahito Yoshinari, and Jun Hata
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Population, 030209 endocrinology & metabolism, Context (language use), Type 2 diabetes, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Diabetes mellitus, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Genetic risk, education, Aged, Proportional Hazards Models, education.field_of_study, Proportional hazards model, business.industry, Incidence (epidemiology), fungi, Biochemistry (medical), Hazard ratio, Middle Aged, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 2, Female, business, Demography
Abstract: Context Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain. Objective This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population. Participants The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002. Design The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95% CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95% CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95% CI, 0.0284 to 0.0494; cNRI, 0.3565; 95% CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors. Conclusions These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population.
Published: 2019
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29. Prevalence of adult epilepsy in a general Japanese population: The Hisayama study

Author: Toshiharu Ninomiya, Akihiro Tanaka, Tomoyuki Ohara, Toshiki Mizuno, Yoichiro Hirakawa, Hiro Kishimoto, Sadatoshi Tsuji, Daigo Yoshida, Takanari Kitazono, Naoko Mukai, Naoki Akamatsu, and Jun Hata
Subjects: First episode, Pediatrics, medicine.medical_specialty, adult epilepsy, business.industry, prevalence, Japanese population, medicine.disease, elderly, Confidence interval, Epilepsy, Health promotion, Neurology, middle‐aged, medicine, Short Research Article, Neurology (clinical), business, Nursing homes, cerebrovascular diseases
Abstract: Summary The aim of the present study was to examine the prevalence and causes of adult epilepsy in a general Japanese population. We examined a total of 3333 Japanese residents in the town of Hisayama aged ≥40 years in 2012‐2013. The examination was performed mainly at the municipal center for health promotion, but some subjects were examined in their homes, hospitals, or nursing homes. Twenty‐three subjects had a diagnosis of epilepsy. The prevalence (95% confidence interval [CI]) of epilepsy per 1000 was 6.9 (4.1‐9.7) in total, 4.9 (1.3‐8.5) in men, and 8.4 (4.3‐12.5) in women (P = 0.23 between sexes). The prevalence of epilepsy was significantly higher in the elderly (aged ≥65 years; 10.3 per 1000 [95% CI 5.4‐15.1]) than in the middle‐aged (aged 40‐64 years; 3.6 per 1000 [95% CI 0.7‐6.4]; P = 0.02). The major cause of epilepsy was cerebrovascular diseases (n = 11; 48% of the epilepsy patients). More than half of the epilepsy patients experienced the first episode of seizure in older age (≥65 years; n = 13; 57%). The findings of this study suggest the clinical importance of the prevention of cerebrovascular diseases to reduce the burden of epilepsy in the future.
Published: 2019
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30. β-Cell Function and Clinical Outcome in Nondiabetic Patients With Acute Ischemic Stroke

Author: Takuya Kiyohara, Ryu Matsuo, Jun Hata, Kuniyuki Nakamura, Yoshinobu Wakisaka, Masahiro Kamouchi, Takanari Kitazono, Tetsuro Ago, Takao Ishitsuka, Setsuro Ibayashi, Kenji Kusuda, Kenichiro Fujii, Tetsuhiko Nagao, Yasushi Okada, Masahiro Yasaka, Ooboshi Hiroaki, Tsuyoshi Omae, Kazunori Toyoda, Hiroshi Nakane, Hiroshi Sugimori, Shuji Arakawa, Kenji Fukuda, Jiro Kitayama, Shigeru Fujimoto, Shoji Arihiro, Junya Kuroda, Yoshihisa Fukushima, and Yasuhiro Kumai
Subjects: Male, β cell function, medicine.medical_specialty, 030204 cardiovascular system & hematology, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Modified Rankin Scale, Internal medicine, medicine, Diabetes Mellitus, Humans, Prospective Studies, Registries, Prospective cohort study, Acute ischemic stroke, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Aged, 80 and over, B-Lymphocytes, business.industry, Odds ratio, Middle Aged, medicine.disease, Hospitalization, Treatment Outcome, Ischemic stroke, Female, Neurology (clinical), Insulin Resistance, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background and Purpose: Little is known about how β-cell dysfunction affects clinical outcome after ischemic stroke. We examined whether β-cell function is associated with clinical outcome after acute ischemic stroke and if so, whether insulin resistance influences this association in a prospective study of patients with acute stroke. Methods: A total of 3590 nondiabetic patients with acute ischemic stroke (mean age, 71 years) were followed up for 3 months. β-Cell function was assessed using the homeostasis model assessment for β-cell function (HOMA-β). Study outcomes were poor functional outcome (modified Rankin Scale score, 3–6) and stroke recurrence at 3 months after stroke onset and neurological deterioration (≥2-point increase in the National Institutes of Health Stroke Scale score) at discharge. Logistic regression analysis was used to evaluate the association between quintile levels of serum HOMA-β and clinical outcomes. Results: The age- and sex-adjusted odds ratios for poor functional outcome and neurological deterioration increased significantly with decreasing HOMA-β levels ( P for trend, Conclusions: Our findings suggest that β-cell dysfunction is significantly associated with poor short-term clinical outcome independently of insulin resistance in nondiabetic patients with acute ischemic stroke.
Published: 2021

31. Urinary N-terminal pro–B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study

Author: Toshiaki Nakano, Jun Hata, Keisuke Yamasaki, Takanari Kitazono, Takanori Honda, Satoko Sakata, Yoichiro Hirakawa, Hiroyuki Tsutsui, Tomomi Ide, Toshiharu Ninomiya, Takuya Nagata, and Daigo Yoshida
Subjects: Adult, Male, medicine.medical_specialty, medicine.drug_class, Urinary system, Population, Urine, 030204 cardiovascular system & hematology, Risk Assessment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Japan, Interquartile range, Internal medicine, Natriuretic Peptide, Brain, Natriuretic peptide, medicine, Humans, Prospective Studies, cardiovascular diseases, 030212 general & internal medicine, Prospective study, education, Aged, Aged, 80 and over, Heart Failure, education.field_of_study, business.industry, Proportional hazards model, Incidence, Hazard ratio, Public Health, Environmental and Occupational Health, Biomarker, General Medicine, General populations, Middle Aged, Cardiovascular disease, Peptide Fragments, Urinary NT-proBNP, Cardiovascular Diseases, Biomarker (medicine), Female, Public aspects of medicine, RA1-1270, business, hormones, hormone substitutes, and hormone antagonists, Biomarkers, Research Article
Abstract: Background Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population. Methods A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007–2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model. Results The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32–104) pg/mL and 20 (18–25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R2] = 0.72): urinary concentrations of 20, 27, and 43 pg/mL were equivalent to serum concentrations of 55, 125, and 300 pg/mL, respectively. During the follow-up period, 170 subjects developed CVD. The age- and sex-adjusted risk of CVD increased significantly with higher urinary NT-proBNP levels (P for trend < 0.001). This association remained significant after adjustment for traditional cardiovascular risk factors (P for trend = 0.009). The multivariable-adjusted risk of developing CVD almost doubled in subjects with urinary NT-proBNP of ≥ 43 pg/mL as compared to those with urinary NT-proBNP of ≤ 19 pg/mL (HR 2.07, 95% CI 1.20–3.56). Conclusions The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.
Published: 2021
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32. Risk Prediction Model for Incident Atrial Fibrillation in a General Japanese Population - The Hisayama Study

Author: Jun Hata, Yoshihiko Furuta, Takanori Honda, Toshiharu Ninomiya, Satoko Sakata, Takuya Nagata, Yoichiro Hirakawa, Takanari Kitazono, Emi Oishi, and Daigo Yoshida
Subjects: medicine.medical_specialty, Waist, Renal function, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Japan, Risk Factors, Internal medicine, Atrial Fibrillation, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Proportional Hazards Models, business.industry, Proportional hazards model, Medical record, Incidence, Atrial fibrillation, General Medicine, Japanese population, medicine.disease, Blood pressure, Cardiology, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: Background The risk prediction of incident atrial fibrillation (AF) is useful to prevent AF and its complications. The aim of this study is to develop a new risk prediction model for incident AF using the prospective longitudinal data from a general Japanese population.Methods and Results:A total of 2,442 community-dwelling AF-free residents aged ≥40 years were followed up from 1988 to 2012 (46,422 person-years). The development of AF was confirmed by a standard 12-lead electrocardiogram at repeated health examinations and by medical records at clinics or hospitals. The risk prediction model for incident AF was developed using a Cox proportional hazards model. During the follow up, 230 AF events were confirmed. Age, sex, systolic blood pressure, waist circumference, estimated glomerular filtration rate, abnormal cardiac murmur, high R-wave amplitude, and arrhythmia other than AF were selected for inclusion in the model. This model showed good discrimination (Harrell's c statistics: 0.785) and calibration (Greenwood-Nam-D'Agostino test: P=0.87) for AF risk at 10 years. Conclusions The new risk prediction model showed good performance on the individual risk assessment of the future onset of AF in a general Japanese population. As this model included commonly used clinical parameters, it may be useful for determining the requirements for the careful evaluation of AF, such as frequent electrocardiogram examinations in clinical settings, and subsequent reductions in the risk of AF-related complications.
Published: 2021

33. Risk prediction for new-onset atrial fibrillation using the Minnesota code electrocardiography classification system

Author: Takahide Fujihashi, Yasuhiko Sakata, Tokiwa Tamai, Takashi Shiroto, Satoshi Yasuda, Hajime Kurosawa, Yu Igarashi, Shinsuke Yamanaka, Hiromasa Ogawa, Shogo Yamada, Toshiya Irokawa, Toshiharu Ninomiya, Kotaro Nochioka, Satoshi Miyata, Hiroaki Shimokawa, Jun Hata, Shinya Ohkouchi, and Hideka Hayashi
Subjects: medicine.medical_specialty, Waist, Epidemiology, Population, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, education, education.field_of_study, Original Paper, Framingham Risk Score, medicine.diagnostic_test, Proportional hazards model, business.industry, Minnesota code, Atrial fibrillation, medicine.disease, Risk factors, RC666-701, Cohort, Risk score, Cardiology and Cardiovascular Medicine, business, Electrocardiography
Abstract: Background Few risk models are available to predict future onset of atrial fibrillation (AF) in workers. We aimed to develop risk prediction models for new-onset AF, using annual health checkup (HC) data with electrocardiogram findings. Methods and Results We retrospectively included 56,288 factory or office workers (mean age = 51.5 years, 33.0% women) who underwent a HC at a medical center and fulfilled the following criteria; age ≥ 40 years, no history of AF, and greater than 1 annual follow-up HC in 2013–2016. Using Cox models with the Akaike information criterion, we developed and compared prediction models for new-onset AF with and without the Minnesota code information. We externally validated the discrimination accuracy of the models in a general Japanese population cohort, the Hisayama cohort. During the median 3.0-year follow-up, 209 (0.37%) workers developed AF. Age, sex, waist circumference, blood pressure, LDL cholesterol, and γ-GTP were associated with new-onset of AF. Using the Minnesota code information, the AUC significantly improved from 0.82 to 0.84 in the derivation cohort and numerically improved from 0.78 to 0.79 in the validation cohort, and from 0.77 to 0.79 in the Hisayama cohort. The NRI and IDI significantly improved in all and male subjects in both the derivation and validation cohorts, and in female subjects in both the validation and the Hisayama cohorts. Conclusions We developed useful risk model with Minnesota code information for predicting new-onset AF from large worker population validated in the original and external cohorts, although study interpretation is limited by small improvement of AUC.
Published: 2021

34. Changes in Body Weight and Concurrent Changes in Cardiovascular Risk Profiles in Community Residents in Japan: the Hisayama Study

Author: Takanori Honda, Masaaki Oda, Yoshihiko Furuta, Satoko Sakata, Yoichiro Hirakawa, Toshiharu Ninomiya, Yuki Ishida, Jun Hata, Emi Oishi, Sanmei Chen, Daigo Yoshida, Takanari Kitazono, and Kenichi Noguchi
Subjects: Adult, Male, Longitudinal study, medicine.medical_specialty, Time Factors, Community resident, Disease, 030204 cardiovascular system & hematology, Body weight, Weight Gain, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Japan, Internal medicine, Weight Loss, Internal Medicine, Medicine, Humans, Longitudinal Studies, Obesity, Aged, business.industry, Biochemistry (medical), Weight change, Middle Aged, medicine.disease, Blood pressure, Cardiovascular Diseases, Heart Disease Risk Factors, Female, Cardiology and Cardiovascular Medicine, business, Body mass index, 030217 neurology & neurosurgery
Abstract: Aim We investigated the influence of weight change on concurrent changes in predicted cardiovascular disease (CVD) risk and individual CVD risk factors over time. Methods A total of 2,140 community-dwellers aged 40-74 years participated in both 2002 and 2007 health examinations. Obesity was defined as body mass index ≥ 25 kg/m2. Weight trajectories were classified as: "stable obese" (obese at both examinations), "obese to nonobese" (obese in 2002 but nonobese in 2007), "nonobese to obese" (nonobese in 2002 but obese in 2007), or "stable nonobese" (nonobese at both examinations). We compared changes in the model-predicted risk for CVD and individual CVD risk factors across weight-change categories. Results The predicted risk for CVD increased during 5 years in all groups; the increment in the predicted risk for CVD was smallest in the obese to nonobese participants and steepest in the nonobese to obese subjects. Compared with the stable obese participants, the obese to nonobese participants had greater favorable changes in waist circumferences, blood pressure, fasting plasma glucose, serum high-density lipoprotein cholesterol, serum triglycerides, and liver enzymes. For all these parameters, opposite trends were observed when comparing the nonobese to obese participants with the stable nonobese group. Conclusions We demonstrated the favorable association of losing weight in obese people and avoiding excessive weight gain in nonobese people with global risk of future CVD and individual CVD risk factors in a real-world setting. The findings could improve behavioral lifestyle interventions that provide information on the health consequences of weight change at health checkups.
Published: 2021

35. Development of a risk prediction model for incident hypertension in Japanese individuals: the Hisayama Study

Author: Jun Hata, Yoichiro Hirakawa, Takanori Honda, Mao Shibata, Yoshihiko Furuta, Toshiharu Ninomiya, Satoko Sakata, Daigo Yoshida, Tomoyuki Ohara, Emi Oishi, Sanmei Chen, and Takanari Kitazono
Subjects: Male, medicine.medical_specialty, Physiology, Blood Pressure, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Japan, Interquartile range, Risk Factors, Internal medicine, Epidemiology, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, Absolute risk reduction, Confidence interval, Blood pressure, Hypertension, Female, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract: The identification of individuals at high risk of developing hypertension can be of great value to improve the efficiency of primary prevention strategies for hypertension. The objective of this study was to develop a risk prediction model for incident hypertension based on prospective longitudinal data from a general Japanese population. A total of 982 subjects aged 40-59 years without hypertension at baseline were followed up for 10 years (2002-12) for the incidence of hypertension. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive agents. The risk prediction model was developed using a Cox proportional hazards model. A simple risk scoring system was also established based on the developed model. During the follow-up period (median 10 years, interquartile range 5-10 years), 302 subjects (120 men and 182 women) developed new-onset hypertension. The risk prediction model for hypertension consisted of age, sex, SBP, DBP, use of glucose-lowering agents, body mass index (BMI), parental history of hypertension, moderate-to-high alcohol intake, and the interaction between age and BMI. The developed model demonstrated good discrimination (Harrell's C statistic=0.812 [95% confidence interval, 0.791-0.834]; optimism-corrected C statistic based on 200 bootstrap samples=0.804) and calibration (Greenwood-Nam-D'Agostino χ2 statistic=12.2). This risk prediction model is a useful guide for estimating an individual's absolute risk for hypertension and could facilitate the management of Japanese individuals at high risk of developing hypertension in the future.
Published: 2020

36. 30-minute postload plasma glucose levels during an oral glucose tolerance test predict the risk of future type 2 diabetes: the Hisayama Study

Author: Takanori Honda, Takanori Teramoto, Satoko Sakata, Hideki Maki, Toshiharu Ninomiya, Shozo Nishimoto, Mayu Higashioka, Mao Shibata, Yoichiro Hirakawa, Hiroyuki Kato, Masahito Yoshinari, Daigo Yoshida, Jun Hata, and Takanari Kitazono
Subjects: Research design, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, oral glucose tolerance test, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Epidemiology, medicine, Humans, Prospective Studies, Oral glucose tolerance, Epidemiology/Health Services Research, Plasma glucose, Proportional hazards model, business.industry, Glucose Tolerance Test, medicine.disease, RC648-665, Quartile, Diabetes Mellitus, Type 2, epidemiology, adult diabetes, business
Abstract: IntroductionTo investigate the associations of 30 min postload plasma glucose (30 mPG) levels during an oral glucose tolerance test (OGTT) with the risk of future diabetes in a general Japanese population.Research design and methodsA total of 2957 Japanese community-dwelling residents without diabetes, aged 40–79 years, participated in the examinations in 2007 and 2008 (participation rate, 77.1%). Among them, 2162 subjects who received 75 g OGTT in a fasting state with measurements of plasma glucose level at 0, 30, and 120 min were followed up for 7 years (2007–2014). Cox’s proportional hazards model was used to estimate HRs and their 95% CIs of each index for the development of type 2 diabetes using continuous variables and quartiles with adjustment for traditional risk factors. The influence of 30 mPG on the predictive ability was estimated with Harrell’s C-statistics, integrated discrimination improvement (IDI), and the continuous net reclassification index (cNRI).ResultsDuring follow-up, 275 subjects experienced type 2 diabetes. Elevated 30 mPG levels were significantly associated with increased risk of developing diabetes (pConclusionsElevated 30 mPG levels were associated with increased risk of diabetes, and inclusion of 30 mPG levels significantly improved the predictive ability for future diabetes, suggesting that 30 mPG may be useful for identifying high-risk populations for type 2 diabetes.
Published: 2020

37. CORRIGENDUM: Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese - The Hisayama Study

Author: Toshiaki Nakano, Yoshihiko Furuta, Daigo Yoshida, Naoki Hirabayashi, Toshiharu Ninomiya, Jun Hata, Tomoyuki Ohara, Keisuke Yamasaki, Yoichiro Hirakawa, and Takanari Kitazono
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Albuminuria, medicine, Cardiology, Brain magnetic resonance imaging, General Medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Hyperintensity
Published: 2020

38. Five-Year Incidence of Myopic Maculopathy in a General Japanese Population: The Hisayama Study

Author: Miho Yasuda, Toshiharu Ninomiya, Tatsuro Ishibashi, Jun Hata, Kohta Fujiwara, Emi Ueda, Koh Hei Sonoda, Sawako Hashimoto, Kyoko Ohno-Matsui, 馬場, 英司, 鴨打, 正浩, and 須藤, 信行
Subjects: Male, Pediatrics, medicine.medical_specialty, Aging, Time Factors, genetic structures, Visual impairment, Population, Visual Acuity, 01 natural sciences, 03 medical and health sciences, Macular Degeneration, 0302 clinical medicine, Asian People, Japan, Risk Factors, medicine, Myopia, Humans, Cumulative incidence, Prospective Studies, 0101 mathematics, Prospective cohort study, education, Original Investigation, Aged, education.field_of_study, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Incidence, 010102 general mathematics, Odds ratio, Middle Aged, medicine.disease, eye diseases, Ophthalmology, Axial Length, Eye, Eye examination, 030221 ophthalmology & optometry, Maculopathy, Female, sense organs, medicine.symptom, business, Follow-Up Studies
Abstract: Importance Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues. Objective To estimate the incidence of myopic maculopathy and its risk factors in Hisayama in southwestern Japan. Design, Setting, and Participants A population-based prospective cohort study in a Japanese community in Hisayama, Japan. The study included a total of 2164 residents 40 years or older who had no myopic maculopathy at the baseline eye examination in 2012 and underwent follow-up eye examinations in 2017. Main Outcomes and Measures Incidence of myopic maculopathy. The grades of myopic maculopathy were categorized based on the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Results The mean (SD) age of the study participants was 62.4 (10.9) years, and the proportion of men was 42.5% (920 participants). In the follow-up examination in 2017, 24 patients developed myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 1.1% (95% CI, 0.6-1.5) overall, 1.4% (95% CI, 0.6-2.2) for men, and 0.9% (95% CI, 0.4-1.4) for women. Multiple logistic regression analysis showed that older age (per 1 year; odds ratio [OR], 1.06; 95% CI, 1.01-1.11) and longer axial length (per 1 mm; OR, 2.94; 95% CI, 2.19-3.95) were associated with incident myopic maculopathy. Conclusions and Relevance Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world.
Published: 2020

39. Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese - The Hisayama Study

Author: Toshiharu Ninomiya, Toshiaki Nakano, Tomoyuki Ohara, Daigo Yoshida, Naoki Hirabayashi, Keisuke Yamasaki, Yoshihiko Furuta, Yoichiro Hirakawa, Takanari Kitazono, and Jun Hata
Subjects: Male, medicine.medical_specialty, Renal function, 030204 cardiovascular system & hematology, Kidney, Risk Assessment, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cognition, Japan, Leukoencephalopathies, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Albuminuria, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Prospective Studies, Cognitive decline, Renal Insufficiency, Chronic, Aged, Aged, 80 and over, Creatinine, business.industry, Confounding, Age Factors, General Medicine, medicine.disease, Magnetic Resonance Imaging, Hyperintensity, Cross-Sectional Studies, chemistry, Cardiology, Microalbuminuria, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers, Kidney disease, Glomerular Filtration Rate
Abstract: BACKGROUND Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality.Methods and Results:In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin : creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV : ICV) ratio, and the association of the combination of UACR and the WMHV : ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV : ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; Ptrend=0.01). In contrast, there was no clear association between eGFR and the WMHV : ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV : ICV ratio (
Published: 2020

40. Serum N-terminal pro-B-type natriuretic peptide as a predictor for future development of atrial fibrillation in a general population: the Hisayama Study

Author: Tomoyuki Ohara, Takanari Kitazono, Daigo Yoshida, Yoshihiko Furuta, Mao Shibata, Jun Hata, Takanori Honda, Toshiharu Ninomiya, Takuya Nagata, Satoko Sakata, Emi Oishi, Hiroyuki Tsutsui, Tomomi Ide, and Yoichiro Hirakawa
Subjects: medicine.medical_specialty, medicine.drug_class, Population, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Atrial Fibrillation, Natriuretic Peptide, Brain, Natriuretic peptide, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Prospective cohort study, education, Aged, education.field_of_study, Proportional hazards model, business.industry, Hazard ratio, Atrial fibrillation, medicine.disease, Peptide Fragments, Biomarker (medicine), Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Biomarkers for predicting future development of atrial fibrillation (AF) have not been fully established in general populations. The aim of this study was to assess the predictive ability of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) for the development of AF.A total of 3126 community-dwelling Japanese subjects aged ≥ 40 years without a history of AF in 2002 were followed up for a median of 10.2 years. Serum NT-proBNP levels at baseline were divided into four categories (≤ 54, 55-124, 125-299, and ≥ 300 pg/mL) according to the current guidelines and prior reports. The hazard ratios for the development of AF were estimated using a Cox proportional hazards model. During the follow-up period, 153 subjects developed new-onset AF. The age- and sex-adjusted cumulative incidence of AF increased significantly with higher serum NT-proBNP levels (p 0.001 for trend). The association remained significant after adjustment for known risk factors for AF and cardiovascular disease (hazard ratio [95% confidence interval]: ≤ 54 pg/mL: 1.00 [reference]; 55-124 pg/mL: 1.72 [1.00-2.97]; 125-299 pg/mL: 3.95 [2.23-6.98]; ≥ 300 pg/mL: 8.51 [4.48-16.17]; p 0.001 for trend). Furthermore, incorporation of serum NT-proBNP levels into the model consisting of known risk factors for AF and cardiovascular disease significantly improved the predictive ability for developing AF (Harrell's c-statistics: 0.828 to 0.844, p = 0.01; continuous net reclassification improvement: 0.41, p 0.001; integrated discrimination improvement: 0.031, p 0.001).Serum NT-proBNP levels can be a risk biomarker for predicting future development of AF in a general Japanese population.
Published: 2020

41. Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study

Author: Takanori Honda, Hajime Yamakage, Jun Hata, Tadashi Teraoka, Takanari Kitazono, Takayuki Inoue, Daigo Yoshida, Mao Shibata, Yoichiro Hirakawa, Shigenobu Kanba, Toru Kusakabe, Toshiharu Ninomiya, Tomoyuki Ohara, Noriko Satoh-Asahara, and Masashi Tanaka
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Microglia, business.industry, Proportional hazards model, Incidence (epidemiology), Hazard ratio, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Neurology, Internal medicine, medicine, Biomarker (medicine), Dementia, Neurology (clinical), Prospective cohort study, Vascular dementia, business, 030217 neurology & neurosurgery
Abstract: Objective To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. Methods A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002-2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. Results During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend 0.11). Interpretation The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47-58.
Published: 2018
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42. Development and validation of modified risk prediction models for cardiovascular disease and its subtypes: The Hisayama Study

Author: Daigo Yoshida, Yoichiro Hirakawa, Takanori Honda, Jun Hata, Takanari Kitazono, Toshiharu Ninomiya, Satoko Sakata, Mao Shibata, and Yuki Ishida
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Coronary Disease, Disease, 030204 cardiovascular system & hematology, Overfitting, Risk Assessment, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Japan, Predictive Value of Tests, Risk Factors, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Internal validity, Prospective cohort study, Stroke, Aged, Aged, 80 and over, business.industry, Public health, Middle Aged, Prognosis, medicine.disease, Blood pressure, Cardiovascular Diseases, Emergency medicine, Female, Cardiology and Cardiovascular Medicine, business, Risk assessment
Abstract: Background and aims Predicting cardiovascular events is of practical benefit for disease prevention. The aim of this study was to develop and evaluate an updated risk prediction model for cardiovascular diseases and its subtypes. Methods A total of 2462 community residents aged 40–84 years were followed up for 24 years. A Cox proportional hazards regression model was used to develop risk prediction models for cardiovascular diseases, and separately for stroke and coronary heart diseases. The risk assessment ability of the developed model was evaluated, and a bootstrapping method was used for internal validation. The predicted risk was translated into a simplified scoring system. A decision curve analysis was used to evaluate clinical usefulness. Results The multivariable model for cardiovascular diseases included age, sex, systolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking habits, and regular exercise as predictors. The models for stroke and coronary heart diseases incorporated both shared and unique variables. The developed models showed good discrimination with little evidence of overfitting (optimism-corrected Harrell's C statistics 0.726–0.777) and calibrations (Hosmer-Lemeshow test, p = 0.44–0.90). The decision curve analysis revealed that the predicted risk-based decision-making would have higher net benefit than either a CVD intervention strategy for all individuals or no individuals. Conclusions The developed risk prediction models showed a good performance and satisfactory internal validity, which may help understand individual risk and setting personalized goals, and promote risk stratification in public health strategies for CVD prevention.
Published: 2018
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43. Objectively measured sedentary time and diabetes mellitus in a general Japanese population: The Hisayama Study

Author: Takanori Honda, Tomoyuki Ohara, Yoichiro Hirakawa, Hiro Kishimoto, Daigo Yoshida, Naoko Mukai, Shuzo Kumagai, Toshiharu Ninomiya, Mao Shibata, and Jun Hata
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Waist, Epidemiology, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Diseases of the endocrine glands. Clinical endocrinology, Sedentary behaviors, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Japan, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Prospective Studies, Aged, Glycated Hemoglobin, business.industry, General Medicine, Odds ratio, Articles, Middle Aged, medicine.disease, RC648-665, Prognosis, Obesity, Confidence interval, Clinical Science and Care, Diabetes Mellitus, Type 2, Original Article, Female, Sedentary Behavior, business, Body mass index, Biomarkers, Follow-Up Studies
Abstract: Aims/Introduction The present study aimed to examine cross‐sectional associations between objectively measured sedentary time and the prevalence of diabetes mellitus in a general Japanese population, and to elucidate possible mediating roles of diet, obesity and insulin resistance in this relationship. Materials and Methods A total of 1,758 community‐dwelling individuals aged 40–79 years wore an accelerometer for ≥7 days and underwent a comprehensive health examination in 2012. Diabetes mellitus was diagnosed by a 75‐g oral glucose tolerance test. The associations of sedentary time with the presence of diabetes mellitus and the levels of the homeostasis model assessment of insulin resistance were estimated by logistic and linear regression models. Results After adjustment for demographic and lifestyle factors including moderate‐to‐vigorous physical activity, participants who spent ≥10 h in sedentary time had a significantly higher odds ratio of the presence of diabetes than those who spent
Published: 2018

44. Association Between Daily Sleep Duration and Risk of Dementia and Mortality in a Japanese Community

Author: Toshiharu Ninomiya, Mao Shibata, Yoichiro Hirakawa, Tomoyuki Ohara, Takanari Kitazono, Daigo Yoshida, Shigenobu Kanba, Naoko Mukai, Hiro Kishimoto, Jun Hata, and Takanori Honda
Subjects: medicine.medical_specialty, medicine.drug_class, Proportional hazards model, business.industry, Hazard ratio, medicine.disease, Hypnotic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Dementia, 030212 general & internal medicine, Geriatrics and Gerontology, Alzheimer's disease, Vascular dementia, Prospective cohort study, business, 030217 neurology & neurosurgery
Abstract: Objectives To investigate the association between daily sleep duration and risk of dementia and death in a Japanese elderly population. Design Prospective cohort study. Setting The Hisayama Study, Japan. Participants Community‐dwelling Japanese individuals aged 60 and older without dementia. Measurements Self‐reported daily sleep duration was grouped into 5 categories (
Published: 2018
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45. The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study

Author: Toshiharu Ninomiya, Masaharu Nagata, Tomoyuki Ohara, Yoichiro Hirakawa, Jun Hata, Yutaka Kiyohara, Hiroyuki Kawano, Takanari Kitazono, Hiro Kishimoto, Daigo Yoshida, and Naoko Mukai
Subjects: Male, Oncology, medicine.medical_specialty, Eicosapentaenoic acid, Epidemiology, 030204 cardiovascular system & hematology, complex mixtures, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Japan, Risk Factors, Internal medicine, Neoplasms, Humans, Medicine, Mortality, Cancer death, health care economics and organizations, Aged, lcsh:R5-920, business.industry, Cancer, social sciences, General Medicine, Middle Aged, medicine.disease, Endocrinology, chemistry, Arachidonic acid, 030220 oncology & carcinogenesis, Cohort studies, Original Article, Female, lipids (amino acids, peptides, and proteins), business, Liver cancer, Cancer risk, lcsh:Medicine (General), Cohort study
Abstract: Background Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations. Methods A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002–2012). The levels of the serum EPA:AA ratio were categorized into quartiles (0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations. Results During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers. Conclusions These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population., Highlights • Lower serum EPA:AA ratio was significantly associated with higher cancer mortality. • The risk of death from liver cancer increased with lower serum EPA:AA ratio. • No significant association was found between serum DHA:AA ratio and cancer death.
Published: 2017

46. Development and validation of a risk assessment tool for gastric cancer in a general Japanese population

Author: Toshiharu Ninomiya, Jun Hata, Fumie Ikeda, Tomoyuki Ohara, Yoichiro Hirakawa, Motohiro Esaki, Koji Yonemoto, Takanari Kitazono, Yutaka Kiyohara, Naoko Mukai, Masahiro Iida, and Daigo Yoshida
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Risk management tools, Risk Assessment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Asian People, Japan, Risk Factors, Stomach Neoplasms, Internal medicine, Epidemiology, medicine, Humans, 030212 general & internal medicine, Risk factor, Aged, Proportional Hazards Models, Framingham Risk Score, biology, Proportional hazards model, business.industry, Incidence, Incidence (epidemiology), Cancer, General Medicine, Middle Aged, Helicobacter pylori, medicine.disease, biology.organism_classification, 030220 oncology & carcinogenesis, Female, business
Abstract: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer–Lemeshow test in the validation cohort. During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend
Published: 2017
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47. Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population

Author: Mao Shibata, Tomoyuki Ohara, Toshiharu Ninomiya, Jun Hata, Toshio Ohtsubo, Masayo Fukuhara, Takanari Kitazono, Daigo Yoshida, Yutaka Kiyohara, Satoko Sakata, and Emi Oishi
Subjects: Male, medicine.medical_specialty, Blood Pressure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Japan, Alzheimer Disease, Risk Factors, Original Research Articles, Physiology (medical), Internal medicine, medicine, Humans, Dementia, Risk factor, Vascular dementia, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Proportional hazards model, Dementia, Vascular, Hazard ratio, Blood Pressure Determination, Middle Aged, medicine.disease, Confidence interval, Surgery, Blood pressure, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, epidemiology, Female, Alzheimer's disease, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Supplemental Digital Content is available in the text., Background: Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia. Methods: A total of 1674 community-dwelling Japanese elderly without dementia, ≥60 years of age, were followed up for 5 years (2007–2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model. Results: During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age- and sex-adjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend
Published: 2017
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48. Dietary Protein Intake and Stroke Risk in a General Japanese Population

Author: Tomoyuki Ohara, Mio Ozawa, Daigo Yoshida, Toshiharu Ninomiya, Jun Hata, Mao Shibata, Masashi Nagata, Kazuhiro Uchida, Naoko Mukai, Takanari Kitazono, and Yutaka Kiyohara
Subjects: Adult, Male, medicine.medical_specialty, Meat, Egg Proteins, Dietary, 030204 cardiovascular system & hematology, Plant Proteins, Dietary, Brain Ischemia, Stroke risk, 03 medical and health sciences, 0302 clinical medicine, Japan, Environmental health, Humans, Medicine, Stroke, Aged, Cerebral Hemorrhage, Advanced and Specialized Nursing, business.industry, Follow up studies, Area of interest, Middle Aged, Japanese population, Milk Proteins, medicine.disease, Diet, Surgery, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Dietary protein intake, Follow-Up Studies, Cohort study
Abstract: Background and Purpose— The influence of dietary protein intake on stroke risk is an area of interest. We investigated the association between dietary protein intake and stroke risk in Japanese, considering sources of protein. Methods— A total of 2400 subjects aged 40 to 79 years were followed up for 19 years. Dietary protein intake was estimated using a 70-item semiquantitative food frequency questionnaire. The risk estimates for incident stroke and its subtypes were calculated using a Cox proportional hazards model. Results— During the follow-up, 254 participants experienced stroke events; of these, 172 had ischemic stroke, and 58 had intracerebral hemorrhage. Higher total protein intake was significantly associated with lower risks of stroke and intracerebral hemorrhage (both P for trend Conclusions— Our findings suggest that higher dietary protein intake is associated with a reduced risk of stroke in the general Japanese population.
Published: 2017
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49. Trends in dementia prevalence, incidence, and survival rate in a Japanese community

Author: Daigo Yoshida, Masaharu Nagata, Toshiharu Ninomiya, Yutaka Kiyohara, Jun Hata, Takanari Kitazono, Shigenobu Kanba, Naoko Mukai, Toru Iwaki, and Tomoyuki Ohara
Subjects: medicine.medical_specialty, business.industry, Cross-sectional study, Incidence (epidemiology), Hazard ratio, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cohort, Medicine, Dementia, 030212 general & internal medicine, Neurology (clinical), Alzheimer's disease, business, Prospective cohort study, Survival rate, 030217 neurology & neurosurgery
Abstract: Objective:To investigate secular trends in the prevalence, incidence, and survival rate of dementia in a Japanese elderly population in a comprehensive manner.Methods:Five cross-sectional surveys of dementia were conducted among residents of a Japanese community, aged ≥65 years, in 1985, 1992, 1998, 2005, and 2012. We also established 2 cohorts consisting of the residents of this age group without dementia in 1988 (n = 803) and 2002 (n = 1,231), and each was followed for 10 years.Results:The age-standardized prevalence of all-cause dementia and Alzheimer disease (AD) increased with time (for all-cause dementia: 6.8% in 1985, 4.6% in 1992, 5.3% in 1998, 8.4% in 2005, and 11.3% in 2012, p for trend p for trend p for trend = 0.59). The age- and sex-adjusted incidence of all-cause dementia and AD, but not VaD, increased from the 1988 cohort to the 2002 cohort (for all-cause dementia: adjusted hazard ratio [aHR] 1.68, 95% confidence interval [CI] 1.38–2.06; for AD: aHR 2.07, 95% CI 1.59–2.70; for VaD: aHR 1.18, 95% CI 0.83–1.69). The 5-year survival rate of all-cause dementia and AD improved from the 1988 cohort to the 2002 cohort (for all-cause dementia: 47.3% to 65.2%; for AD: 50.7% to 75.1%; all p < 0.01).Conclusions:The increased incidence and improved survival rate of AD could have resulted in the steep increase in AD prevalence in the Japanese elderly.
Published: 2017
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50. Tooth Loss and Risk of Dementia in the Community: the Hisayama Study

Author: Tomoyuki Ohara, Kenji Takeuchi, Toshiharu Ninomiya, Yukie Shibata, Daigo Yoshida, Toru Takeshita, Michiko Furuta, Yoshihisa Yamashita, and Jun Hata
Subjects: Male, medicine.medical_specialty, Dentistry, Neuropsychological Tests, Tooth Loss, 03 medical and health sciences, 0302 clinical medicine, Asian People, Japan, stomatognathic system, Risk Factors, Internal medicine, Epidemiology, medicine, Tooth loss, Humans, Dementia, Longitudinal Studies, Prospective Studies, Prospective cohort study, Vascular dementia, Aged, business.industry, Proportional hazards model, Confounding, Hazard ratio, 030206 dentistry, Middle Aged, medicine.disease, stomatognathic diseases, Female, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Objectives To clarify the effect of tooth loss on development of all-cause dementia and its subtypes in an elderly Japanese population. Design Prospective cohort study. Setting The Hisayama Study, Japan. Participants Community-dwelling Japanese adults without dementia aged 60 and older (N = 1,566) were followed for 5 years (2007–2012). Measurements Participants were classified into four categories according to baseline number of remaining teeth (≥20, 10–19, 1–9, 0). The risk estimates of the effect of tooth loss on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model. Results During follow-up, 180 (11.5%) subjects developed all-cause dementia; 127 (8.1%) had AD, and 42 (2.7%) had VaD. After adjusting for potential confounders, there was a tendency for the multivariable-adjusted hazard ratio of all-cause dementia to increase with decrease in number of remaining teeth (P for trend = .04). The risk of all-cause dementia was 1.62 times as great in subjects with 10 to 19 teeth, 1.81 times as great in those with one to nine teeth, and 1.63 times as great in those with no teeth as in those with 20 teeth or more. An inverse association was observed between number of remaining teeth and risk of AD (P for trend = .08), but no such association was observed with risk of VaD (P for trend = .20). Conclusion Tooth loss is associated with an increased risk of all-cause dementia and AD in the Japanese population.
Published: 2017
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