Search

The real-world effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in Japan remains unclear. This case–control study evaluated the vaccine effectiveness (VE) of two doses of mRNA vaccine, BNT162b2 or mRNA-1273, against the delta (B.1.617.2) variant in the Japanese general population in the period June–September 2021. Individuals in close contact with COVID-19 patients were tested using polymerase chain reaction (PCR). A self-administered questionnaire evaluated vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, and living environment. Two vaccine doses were reported by 11.6% of cases (n = 389) and 35.2% of controls (n = 179). Compared with controls, cases were younger and had a lower proportion who always performed handwashing for ≥20 s, a higher proportion of alcohol consumers, and a lower proportion of individuals living in single-family homes or with commuting family members. After adjusting for these confounding factors and day of PCR testing by multivariate logistic regression analysis, the VE in the period June–July (delta variant proportion 45%) was 92% and 79% in the period August–September (delta variant proportion 89%). The adjusted VE for homestay, hotel-based isolation and quarantine, and hospitalization was 78%, 77%, and 97%, respectively. Despite declining slightly, VE against hospitalization remained robust for ~3 months after the second dose. Vaccination policymaking will require longer-term monitoring of VE against new variants. [ABSTRACT FROM AUTHOR]

Purpose: In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations. Methods: To elucidate the clinical usefulness of in vitro‐fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen‐thawed 1PN‐ and 0PN‐derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan. Results: The rates of pregnancy and live birth for 1PN‐derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 0PN‐derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN‐derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 1PN‐derived blastocysts were significantly lower (4.0% for both) than those for 2PN‐ and 0PN‐derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN‐ or 1PN‐derived blastocysts. Conclusions: Both 1PN‐ and 0PN‐derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN‐derived blastocysts, especially if they are obtained by ICSI. [ABSTRACT FROM AUTHOR]

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 (<5.0, 5.0–6.9, 7.0–7.9, 8.0–9.9, ≥10.0 hours). The association between daily sleep duration and risk of dementia and death was determined using a Cox proportional hazards models. Results: During follow‐up, 294 participants developed dementia, and 282 died. Age‐ and sex‐adjusted incidence rates of dementia and all‐cause mortality were significantly greater in subjects with daily sleep duration of less than 5.0 hours and 10.0 hours and more than in those with daily sleep duration of 5.0 to 6.9 hours. These associations remained unchanged after adjustment for potential confounding factors (<5.0 hours: hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.38–5.05 for dementia; HR=2.29, 95% CI=1.15–4.56 for death; ≥10.0 hours: HR=2.23, 95% CI=1.42–3.49 for dementia; HR=1.67, 95% CI=1.07–2.60 for death). Similar U‐shaped associations were observed for Alzheimer's disease and vascular dementia. With regard to the influence of hypnotic use on risk of dementia and death, subjects who used hypnotics and had any sleep duration had a risk of dementia that was 1.66 times as great and a risk of death that was 1.83 times as great as those who did not use hypnotics and had a daily sleep duration of 5.0 to 6.9 hours. Conclusion: Short and long daily sleep duration and hypnotic use are risk factors for dementia and death in Japanese elderly adults. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between diabetes and brain or hippocampal atrophy in an elderly population.Research Design and Methods: A total of 1,238 community-dwelling Japanese subjects aged ≥65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders.Results: The multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P < 0.01). These three ratios decreased significantly with elevated 2-h postload glucose (PG) levels (all P for trend <0.05) but not fasting plasma glucose levels. Longer duration of diabetes was significantly associated with lower TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios. The subjects with diabetes diagnosed in midlife had significantly lower HV-to-ICV and HV-to-TBV ratios than those without and those diagnosed in late life.Conclusions: Our data suggest that a longer duration of diabetes and elevated 2-h PG levels, a marker of postprandial hyperglycemia, are risk factors for brain atrophy, particularly hippocampal atrophy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To clarify the association between midlife and late-life smoking and risk of dementia. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, Japan. PARTICIPANTS: Japanese community-dwellers without dementia aged 65 to 84 (mean age 72) followed for 17 years (1988-2005) (N = 754), 619 of whom had participated in a health examination conducted in 1973-74 (mean age, 57) and were included in the midlife analysis. MEASUREMENTS: The risk estimates of smoking status on the development of dementia were computed using a Cox proportional hazards model. RESULTS: During follow-up, 252 subjects developed all-cause dementia; 143 had Alzheimer's disease (AD), and 76 had vascular dementia (VaD). In late life, the multi-variable-adjusted risk of all-cause dementia was significantly greater in current smokers than in never smokers; similar associations were seen for all-cause dementia, AD, and VaD in midlife current smokers. Meanwhile, no significant association was observed between past smoking and risk of any type of dementia in late or midlife. Multivariable analysis showed that smokers in midlife and late life had significantly greater risks than lifelong nonsmokers of all-cause dementia (adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI) = 1.49-3.49), AD (aHR = 1.98, 95% CI = 1.09-3.61), and VaD (aHR = 2.88, 95% CI = 1.34-6.20). Such associations were not observed for midlife smokers who quit smoking in late life. CONCLUSION: Persistent smoking from mid- to late life is a significant risk factor for dementia and its subtypes in the general Japanese population. [ABSTRACT FROM AUTHOR]

Aims Periodontal disease and metabolic syndrome ( MS) are more prevalent in males than in females. However, whether there is a gender difference in the association between these health conditions has not yet been investigated. This study examined the gender difference in this association, considering the definition of periodontal disease. Materials and Methods We recruited 1040 males and 1330 females, aged ≥40 years, with at least ten teeth from subjects of the 2007 Hisayama health examination. We performed a logistic regression analysis with various definitions of periodontal disease the dependent variable and MS as the independent variable. Following the analysis, the data were reanalysed with the structural equations model. Results The logistic regression analysis suggested a stronger association between periodontal disease and MS in females than that in males when periodontal disease was more severely defined. When we constructed the structural equations model in each gender, the model showed a good fit to the data of females, suggesting the association between periodontal disease and MS in females, but not in males. Conclusions Gender differences seem to exist in the association between periodontal disease and MS; MS might show a stronger association with periodontal disease in females than in males. [ABSTRACT FROM AUTHOR]

The authors examined the associations of glucose tolerance status and fasting and 2-hour postload glucose levels with the risk of cancer death in a 19-year follow-up study of 2,438 Japanese subjects aged 40–79 years who underwent a 75-g oral glucose tolerance test (1988–2007). During follow-up, 229 subjects died of cancer. The risk of cancer death was significantly higher in subjects with fasting plasma glucose levels of ≥5.6 mmol/L or 2-hour postload glucose levels of ≥11.1 mmol/L than in those with the lowest fasting or 2-hour postload glucose levels, after adjustment for potentially confounding factors. According to glucose tolerance status, not only diabetes but also impaired fasting glycemia and impaired glucose tolerance were significant risk factors for cancer death (for impaired fasting glycemia, multivariable-adjusted hazard ratio (HR) = 1.49 (95% confidence interval (CI): 1.05, 2.11); for impaired glucose tolerance, HR = 1.52 (95% CI: 1.05, 2.22); and for diabetes, HR = 2.10 (95% CI: 1.41, 3.12)). With regard to site-specific cancers, elevated fasting or 2-hour postload glucose levels were associated with the risks of death from stomach, liver, and lung cancer. These findings suggest that both prediabetic hyperglycemia and diabetes are significant risk factors for cancer death in the general Japanese population. [ABSTRACT FROM PUBLISHER]

Background: Cigarette smoking is an established risk factor for stroke and coronary heart disease (CHD) in Western countries. However, it is uncertain whether or not smoking raises the risk of stroke in Japanese. We examined the influence of smoking on the development of stroke and CHD and the effects of interactions between smoking and hypercholesterolemia on these outcomes in a general Japanese population. Methods: A total of 2,421 community-dwelling Japanese individuals, aged 40-79 years, with no history of cardiovascular disease, were followed up for 14 years. Results: During the follow-up, 194 total stroke and 112 CHD events occurred. Compared with never smokers, the multivariate-adjusted hazard ratios for the occurrence of total stroke were 1.53 (95% confidence interval = 0.90-2.61) in former smokers, 1.90 (1.18-3.06) in current light smokers (<20 cigarettes/day) and 2.01 (1.11-3.65) in current heavy smokers (≥20 cigarettes/day). The multivariate-adjusted hazard ratios for the development of CHD were 1.10 (0.56-2.15), 1.88 (1.02-3.47) and 2.31 (1.17-4.57), respectively. In regard to stroke subtypes, current smoking was an independently significant risk factor for ischemic stroke and subarachnoid hemorrhage. Furthermore, the combination of smoking and hypercholesterolemia synergistically increased the risks of total stroke and CHD (all p for interaction <0.05). Conclusion: Our findings suggest that smoking raises the risks of ischemic stroke, subarachnoid hemorrhage and CHD occurrence in the Japanese population, and that this effect is strengthened by hypercholesterolemia. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS--A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16-2.71, 2.72-3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM. RESULTS--In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14-2.85; P = 0.01). CONCLUSIONS--Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: 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., Methods: 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., Results: 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., Conclusions/interpretation: 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.

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 < 0.001), whereas there was no significant association between α-cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2-h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (all P < 0.01)., Conclusions: β-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining β-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

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 <6 h in sedentary time (odds ratio 1.84, 95% confidence interval 1.02-3.31). This significant association remained after adjusting for overall and central obesity (as measured by body mass index and waist circumference), but weakened after adjusting for dietary energy intake or homeostasis model assessment of insulin resistance. Sedentary time was positively associated with homeostasis model assessment of insulin resistance levels among non-diabetic participants after adjusted for obesity or energy intake (P for trend <0.01)., Conclusions: Longer sedentary time was associated with a higher prevalence of diabetes mellitus in a general Japanese population. Insulin resistance appeared to be mainly involved in this association. These results highlight the importance of public health strategies targeting reductions in sedentary time for the primary prevention of diabetes mellitus., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: The purpose of this study was to describe changes in physical activity volumes and sedentary time over 3 years in the middle-aged and older Japanese population., Methods: Study participants included 1151 Japanese community-dwelling residents aged ≥40 years in 2009 who underwent 2 sets of health examinations (2009 and 2012). Using a triaxial accelerometer, longitudinal changes in sedentary time, light physical activity volume, moderate to vigorous physical activity volume, number of steps, and total physical activity volume were evaluated according to sex, age (40-49, 50-59, 60-69, 70-79, and ≥80 y), and obese (nonobese and obese) categories., Results: Sedentary time significantly increased, and all physical activity volumes significantly decreased among all participants. Although most variables did not change significantly in the 40-49 and 50-59 year age categories, similar changes as all participants were observed across all other categories. In the correlation analyses, changes in sedentary time correlated, at most, only modestly for each change in physical activity volumes, indicating that increased physical activity volume does not always lead to decreased sedentary time, and vice versa., Conclusions: Strategies to reduce sedentary time and promote physical activity are needed in Japan, particularly for people aged ≥60 years.

Background: Epidemiological evidence suggests that fish consumption and intake of n-3 polyunsaturated fatty acids (PUFA)-namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-confer protection against depression. However, few studies have addressed the influence of the balance between n-3 PUFA and n-6 PUFA in the human body on depression., Methods: A total of 2,529 community-dwelling Japanese residents aged ≥ 40 years were assessed for depressive symptoms (defined as a score of 16 points or more on the Center for Epidemiologic Studies Depression Scale [CES-D]) in 2007. The serum arachidonic acid (AA) /EPA ratio and AA/DHA ratio were measured in frozen samples collected in 2002 and categorized into quartiles. The odds ratios (ORs) for the presence of depressive symptoms were calculated using a logistic regression model., Results: The prevalence of depressive symptoms was 4.3%. There was no significant association between either the serum AA/EPA ratio or AA/DHA ratio and the presence of depressive symptoms. However, subjects with the highest serum AA/EPA ratios (range: 3.28-13.3) had a 4.10 times (95%CI: 1.13-19.80) greater OR for the presence of depressive symptoms than those with the lowest ratios (0.30-1.65) after adjusting for confounding factors in the subgroup with high-sensitivity C-reactive protein (hs-CRP) ≥ 1.0 mg/L, while no clear association was observed in the subgroup with hs-CRP < 1.0 mg/L., Limitations: Reverse causality is possible due to the cross-sectional study design., Conclusions: Our findings suggest that a higher serum AA/EPA ratio is associated with a greater likelihood of depressive symptoms in subjects with systemic inflammation in the general Japanese population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: We aimed to investigate secular trends in the incidence, risk factors, and prognosis of transient ischemic attack (TIA) in a general Japanese population., Methods: Two cohorts consisting of stroke-free Japanese individuals aged ≥40 years in 1961 (n = 1621) and 1988 (n = 2646) were followed up for 24 years. The associations of potential risk factors with the development of TIA were estimated by a Cox proportional hazards model. The influence of TIA on the risk of total stroke over the subsequent 10 years was compared between the sub-cohorts of subjects with TIA and age- and sex-matched control subjects from each cohort., Results: During follow-up, 28 subjects in the 1961 cohort and 34 in the 1988 cohort experienced TIA. The age-standardized incidence of TIA was significantly lower in the 1988 cohort than the 1961 cohort (0.66 vs. 1.01 per 1000 person-years, p = 0.02). While elevated systolic blood pressure was significantly associated with the risk of TIA in both cohorts, glucose intolerance and higher serum cholesterol levels were associated with TIA risk only in the 1988 cohort. The subjects experiencing TIA had approximately 7-8-fold higher risks for the 10-year incidence of total and ischemic strokes compared with the corresponding control subjects without TIA both in the 1961 and 1988 sub-cohorts, and the relative risks were not significantly different between sub-cohorts., Conclusions: Our results suggest that the incidence of TIA decreased during the past half century, probably due to the spread of antihypertensive treatments in the general Japanese population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: 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., Methods: 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., Results: 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 < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort., Conclusions: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual's risk of future gastric cancer.

Background: Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD)., Methods and Results: A total of 1562 community-dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all-cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin-creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow-up, 358 subjects developed all-cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable-adjusted risks of all-cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78-1.60], 1.65 [1.18-2.30], and 1.56 [1.11-2.19] for UACR of ≤6.9, 7.0-12.7, 12.8-29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77-1.86], 1.75 [1.16-2.64], and 1.58 [1.03-2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46-2.29], 1.94 [0.96-3.95], and 2.19 [1.09-4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of <60 mL/min per 1.73 m 2 had 3.3-fold greater risk of VaD than those with UACR <12.8 mg/g and eGFR of ≥60 mL/min per 1.73 m 2 ., Conclusions: Albuminuria is a significant risk factor for the development of both AD and VaD in community-dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH) 2 D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH) 2 D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 than in those with eGFR ≥60 mL/min/1.73 m 2 ; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04)., Conclusions: The findings suggested that a lower serum 1,25(OH) 2 D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH) 2 D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.

Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD)., Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years., Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status., Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD., (Copyright © 2017 Endocrine Society)

Background: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population., Methods: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years., Results: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001)., Conclusions: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.

Objective: Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population., Approach and Results: A total of 3005 community-dwelling Japanese aged ≥40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80-2.04]; Q3, 1.48 [0.95-2.32]; and Q4, 1.85 [1.20-2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76-1.94]; Q3, 1.38 [0.87-2.17]; and Q4, 1.66 [1.05-2.60]; P=0.02 for trend)., Conclusions: Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation., (© 2016 American Heart Association, Inc.)

Objectives: The association between hematocrit levels and the risk of cardiovascular disease (CVD) has been reported inconsistently. We aimed to investigate the association of hematocrit levels with the development of stroke and coronary heart disease (CHD) in a general Japanese population., Methods: A total of 2585 community-dwelling Japanese individuals aged 40 years or older in 1988 were followed up for 19 years. These subjects were divided into four groups according to the sex-specific quartiles of hematocrit at baseline., Results: During the follow-up, 301 subjects developed stroke (210 ischemic and 91 hemorrhagic) and 187 developed CHD. The risk of ischemic stroke was higher in both the lowest (Q1: men, ≤44.7%; women, ≤39.3%) and the highest (Q4: men, ≥49.7%; women, ≥43.8%) quartiles than in the third quartile (Q3: men, 47.1%-49.6%; women, 41.7%-43.7%) used as a reference (multivariable-adjusted hazard ratios [95% confidence intervals]: Q1, 1.55 [0.99-2.43]; Q2, 1.44 [0.93-2.23]; Q3, 1.00; and Q4, 1.62 [1.06-2.50]; P = 0.86 for trend). In contrast, hematocrit levels and the risk of hemorrhagic stroke showed a linear inverse association (Q1, 1.91 [1.03-3.54]; Q2, 1.26 [0.68-2.34]; Q3, 1.00; and Q4, 0.81 [0.41-1.61]; P = 0.009 for trend). The risk of CHD increased significantly in Q4 (Q1, 1.13 [0.71-1.80]; Q2, 1.08 [0.69-1.71]; Q3, 1.00; and Q4, 1.60 [1.04-2.46]; P = 0.13 for trend)., Conclusions: Our findings suggest that both elevated and decreased hematocrit levels are associated with an increased risk of CVD, but the influence of hematocrit is different among subtypes of CVD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: It is not clear which glucose measure is more useful in the assessment of atherosclerosis. We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), fasting plasma glucose (FPG), and 2-hour postload glucose (PG) with carotid intima-media thickness (IMT) in community-dwelling Japanese subjects., Methods: A total of 2702 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test and measurements of HbA1c, GA, 1,5-AG, and carotid IMT by ultrasonography in 2007-2008. Carotid wall thickening was defined as a maximum IMT of >1.0 mm. The crude and multivariable-adjusted linear and logistic regression models were used to analyze cross-sectional associations between levels of glycemic measures and carotid IMT., Results: The crude average of the maximum IMT increased significantly with rising quartiles of HbA1c, GA, FPG, and 2-hour PG levels in subjects with and without glucose intolerance (GI), while no clear association was observed for 1,5-AG. After adjustment for other confounding factors, positive trends for HbA1c, GA, and FPG (all p for trend < 0.05), but not 2-hour PG (p = 0.07) remained robust in subjects with GI, but no such associations were found in those without GI. When estimating multivariable-adjusted β values for the associations of 1 SD change in glycemic measures with the maximum IMT in subjects with GI, the magnitude of the influence of HbA1c (β = 0.021), GA (β = 0.024), and FPG (β = 0.024) was larger than that of 2-hour PG (β = 0.014) and 1,5-AG (β = 0.003). The multivariable-adjusted odds ratios for the presence of carotid wall thickening increased significantly with elevating HbA1c, GA, and FPG levels only in subjects with GI (all p for trend < 0.001). Among subjects with GI, the area under the receiver operating characteristic curve significantly increased by adding HbA1c (p = 0.04) or GA (p = 0.04), but not 1,5-AG, FPG, or 2-hour PG, to the model including other cardiovascular risk factors., Conclusions: In community-dwelling Japanese subjects with GI, elevated HbA1c, GA, and FPG levels were significantly associated with increased carotid IMT, and HbA1c and GA provided superior discrimination for carotid wall thickening compared to 1,5-AG, FPG, and 2-hour PG, suggesting that HbA1c and GA are useful for assessing carotid atherosclerosis.

Objectives: To determine the effect of milk and dairy intake on the development of all-cause dementia and its subtypes in an elderly Japanese population., Design: Prospective cohort study., Setting: The Hisayama Study, Japan., Participants: Individuals aged 60 and older without dementia (N = 1,081)., Measurements: Milk and dairy intake was estimated using a 70-item semiquantitative food frequency questionnaire grouped into quartiles. The risk estimates of milk and dairy intake on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model., Results: Over 17 years of follow-up, 303 subjects developed all-cause dementia; 166 had AD, and 98 had VaD. The age- and sex-adjusted incidence of all-cause dementia, AD, and VaD significantly decreased as milk and dairy intake level increased (P for trend = .03 for all-cause dementia, .04 for AD, .01 for VaD). After adjusting for potential confounders, the linear relationship between milk and dairy intake and development of AD remained significant (P for trend = .03), whereas the relationships with all-cause dementia and VaD were not significant. The risk of AD was significantly lower in the second, third, and fourth quartiles of milk and dairy intake than in the first quartile., Conclusion: Greater milk and dairy intake reduced the risk of dementia, especially AD, in the general Japanese population., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Background and Purpose: It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan., Methods: A total of 2452 community-dwelling Japanese subjects aged≥40 years were followed prospectively for 24 years., Results: The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend<0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend<0.01), and such tendency was seen for atherothrombotic infarction (P for trend=0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend=0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations=1.17, 95% confidence interval (CI)=1.02 to 1.35], atherothrombotic infarction (adjusted HR=1.39, 95% CI=1.09 to 1.79), and cardioembolic infarction (adjusted HR=0.64, 95% CI=0.47 to 0.85)., Conclusions: Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: There has been controversy over the diagnostic thresholds of hemoglobin A1c (HbA1c) for diabetes. In addition, no study has examined the thresholds of glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) for diagnosing diabetes using the presence of diabetic retinopathy (DR). We examined the optimal thresholds of various glycemic measures for diagnosing diabetes based on the prevalence of DR in community-dwelling Japanese subjects., Methods: A total of 2,681 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test, measurement of HbA1c, GA, and 1,5-AG, and an ophthalmic examination in 2007-2008. The associations of glycemic measures with DR status were examined cross-sectionally. DR was assessed by an examination of the fundus photograph of each eye and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. We divided the values of glycemic measures into ten groups on the basis of deciles. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold of each glycemic measure for detecting the presence of DR., Results: Of the subjects, 52 had DR. The prevalence of DR increased steeply above the ninth decile for fasting plasma glucose (FPG) (6.2-6.8 mmol/l), for 2-hour postload glucose (PG) (9.2-12.4 mmol/l), for HbA1c (5.9-6.2% [41-44 mmol/mol]), and for GA (16.2-17.5%), and below the second decile for 1,5-AG (9.6-13.5 μg/mL). The ROC curve analysis showed that the optimal thresholds for DR were 6.5 mmol/l for FPG, 11.5 mmol/l for 2-hour PG, 6.1% (43 mmol/mol) for HbA1c, 17.0% for GA, and 12.1 μg/mL for 1,5-AG. The area under the ROC curve (AUC) for 2-hour PG (0.947) was significantly larger than that for FPG (0.908), GA (0.906), and 1,5-AG (0.881), and was marginally significantly higher than that for HbA1c (0.919). The AUCs for FPG, HbA1c, GA, and 1,5-AG were not significantly different., Conclusions: Our findings suggest that the FPG and HbA1c thresholds for diagnosing diabetes in the Japanese population are lower than the current diagnostic criterion, while the 2-hour PG threshold is comparable with the diagnostic criterion. 2-hour PG had the highest discriminative ability, whereas FPG, HbA1c, GA, and 1,5-AG were similar in their ability.

Background: No previous population-based studies have examined secular trends in the incidence of intracerebral hemorrhage (ICH) by its location., Methods and Results:  We established 3 cohorts consisting of residents of Hisayama, Japan, aged ≥40 years without a history of stroke or myocardial infarction in 1961 (the first cohort, n=1,618), in 1974 (the second cohort, n=2,038), and in 1988 (the third cohort, n=2,637). Each cohort was followed for 13 years. The age- and sex-adjusted incidence of ICH significantly declined from the first to the second cohort and showed no further change in the third cohort. With regard to the ICH location, the incidence of putaminal hemorrhage decreased steadily, mainly in subjects aged 60-69 years, whereas the incidence of thalamic hemorrhage increased, especially in those aged ≥70 years. Both hypertension and alcohol intake were strong risk factors for ICH in the first cohort, but their influence declined with time. Blood pressure levels in hypertensive subjects decreased significantly, and the proportion of current drinkers decreased slightly over the study period., Conclusions: Our findings suggest that the ICH incidence steeply declined from the 1960s to the 1970s in Japan as a result of the reduced influence of hypertension and alcohol intake, but that this decline has leveled off since then, probably because of the increased incidence of thalamic hemorrhage in the elderly in recent years.

Aim: Peripheral artery disease (PAD), defined as a decreased ankle brachial index (ABI), is a risk factor for cardiovascular disease; however, few studies have assessed the relationship between a low ABI and cardiovascular risks in Asian populations. We herein examined the relationship between the ABI and the development of cardiovascular disease in a Japanese community., Methods: A total of 2,954community-dwelling Japanese individuals without prior cardiovascular disease ≥ 40years of age were followed up for an average of 7.1years. The subjects' ABIs were categorized into the three groups: low (≤0.90), borderline (0.91-0.99) and normal (1.00-1.40). We estimated the relationship between the ABI and cardiovascular risk using a Cox proportional hazards model., Results: During the follow-up period, 134subjects experienced cardiovascular events. The incidence of cardiovascular disease across the ABI values was significantly different (p＜0.001). After adjusting for confounding factors, namely age, sex, systolic blood pressure, use of anti-hypertensive drugs, diabetes, total cholesterol, high-density lipoprotein cholesterol, obesity, smoking, alcohol intake and regular exercise, individuals with a low ABI were at 2.40-fold (95% confidence interval [CI] 1.14-5.06) greater risk of cardiovascular disease and 4.13-fold (95% CI 1.62-10.55) greater risk of coronary heart disease., Conclusions: Our findings suggest that individuals with an ABI of ≤ 0.90 have an increased risk of cardiovascular events, independent from traditional risk factors, in the general Japanese population.

Objective: We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population., Methods: A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model., Results: During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0 mg/L (p for trend = 0.006), whereas no clear association was observed in those with HS-CRP of <1.0 mg/L (p for trend = 0.27). The multivariable-adjusted risk of cardiovascular disease increased significantly, by 1.52 times (95% confidence interval 1.12-2.04) per 0.20 decrement in serum EPA/AA ratio in subjects with HS-CRP of ≥1.0 mg/L. A lower serum EPA/AA ratio was significantly associated with an increased risk of coronary heart disease, but there was no evidence of an association with stroke. The magnitude of the influence of the serum EPA/AA ratio on the cardiovascular risk increased significantly with elevating HS-CRP levels taken as a continuous variable (p for heterogeneity = 0.007). However, no such association was observed for DHA/AA ratio., Conclusion: Our findings suggest that a lower serum EPA/AA ratio is associated with a greater risk of cardiovascular disease, especially coronary heart disease, among subjects with higher HS-CRP levels in the general Japanese population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: There is little information about predictive ability of haemoglobin A1c (HbA1c) for cardiovascular disease (CVD) in Asians. To investigate the discriminatory ability of HbA1c to identify subjects who are at greater risk of developing CVD in a prospective study of a defined community-dwelling Japanese population., Methods: A total of 2,851 subjects aged 40-79 years were stratified into five groups (HbA1c levels with ≤ 5.0, 5.1-5.4, 5.5-6.4, and ≥ 6.5% and a group with antidiabetic medication) and followed up prospectively for 7 years (2002-2009)., Results: During the follow-up, 119 subjects developed CVD. The multivariable-adjusted risk of CVD was significantly increased in subjects with HbA1c levels of 5.5-6.4 and ≥ 6.5% and diabetic medication compared to HbA1c level with ≤ 5.0% (hazard ratio, 2.26 [95% confidence interval, 1.29-3.95] for the 5.5-6.4%; 4.43 [2.09-9.37] for the ≥ 6.5%; and 5.15 [2.65-10.0] for the antidiabetic medication group). With regard to CVD subtype, the positive associations between HbA1c levels and the risk of coronary heart disease (CHD) and ischaemic stroke were also significant, but no such associations were seen for haemorrhagic stroke. The C statistic for developing CVD was significantly increased by adding HbA1c values to the model including other risk factors (0.789 vs. 0762, p = 0.006), and the net reclassification improvement was 0.105 (p = 0.004)., Conclusions: Our findings suggest that elevated HbA1c levels are an independent risk factor for CVD, especially CHD and ischaemic stroke, and that the addition of HbA1c to the model with traditional risk factors significantly improves the predictive ability of CVD.

Background: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan., Methods and Results: We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply., Conclusions: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

Background: Studies addressing the temporal trends in the prevalence of sudden unexpected death (SUD) and its underlying causes in the general population are limited., Methods: Among a total of 1934 residents aged ≥20 years of the town of Hisayama, Japan, who died of endogenous causes of death and underwent autopsy examination (autopsy rate 78.5%) from 1962 to 2009, 204 were determined to be cases of SUD within 24 hours., Results: The trend in the age- and sex-adjusted prevalence of SUD among all autopsy subjects was stable over four 12-year periods (13.1% in 1962-1973, 13.4% in 1974-1985, 15.0% in 1986-1997, and 14.6% in 1998-2009; P for trend = .80). Regarding causes of death, the prevalence of SUD from stroke significantly declined with time (8.0%, 5.0%, 2.3%, and 2.1%, respectively; P for trend < .001), whereas significant increments were observed in the prevalence of SUD from heart disease (4.0%, 6.2%, 8.6%, and 9.7%; P for trend = .02) and from aortic aneurysm and dissection (0.2%, 1.2%, 2.9%, and 2.8%; P for trend = .01). In particular, the prevalence of ischemic heart disease increased 3-fold from 2.1% in 1962-1973 to 6.6% in 1998-2009 (P = .04). Reflecting the increment of ischemic heart disease, SUD within 1 hour increased significantly from 2.5% to 7.6% during this period (P = .01)., Conclusions: The trend in the prevalence of SUD was stable across a half century in a general Japanese population. Despite the decrement in the prevalence of SUD from stroke, that from heart disease, especially ischemic heart disease, increased significantly with time., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Aims: Although several surrogate measures of insulin resistance have been proposed, their associations with cardiovascular disease (CVD) have not been evaluated sufficiently., Methods: A total of 2,356 community-dwelling Japanese individuals aged 40 to 79 years who underwent a 75 g oral glucose tolerance test were followed up for 14 years. The status of insulin resistance was estimated by using the Matsuda index or homeostasis model assessment of insulin resistance (HOMA-IR)., Results: During follow-up, 260 subjects developed CVD. The age- and sex-adjusted hazard ratios of CVD significantly decreased with an increasing Matsuda index and rose with increasing HOMA-IR levels (both p for trend <0.05). After adjustment for age, sex, serum total cholesterol, electrocardiogram abnormalities, proteinuria, smoking habits, alcohol intake, and regular exercise, the risk of CVD was significantly lower in the third to fifth quintiles of the Matsuda index and higher in the fifth quintile of HOMA-IR values compared with the first quintile of the corresponding index (Matsuda index Q3: hazard ratio (HR)= 0.59 [95% confidence interval 0.40-0.87]; Q4: HR= 0.66 [0.45-0.97]; and Q5: HR= 0.67 [0.47-0.97]; HOMA-IR Q5: HR= 1.55 [1.05-2.29]); however, these associations were attenuated after further adjustment for the metabolic syndrome status. In regard to CVD subtypes, the risks for stroke and coronary heart disease significantly decreased with an increasing Matsuda index, while elevated HOMA-IR levels were a significant risk factor for stroke, but not for coronary heart disease., Conclusion: Our findings suggest that insulin resistance significantly increases the risk of incident CVD through metabolic syndrome in Japanese.

Background: There are limited data on the prevalence and causes of disability in the elderly general population in Japan., Methods: In a population-based cross-sectional study of 1550 Japanese aged 65 years or older, we examined the prevalence of functional disability (defined as a Barthel Index score of ≤95) and its causes., Results: A total of 311 of the participants had a disability (prevalence 20.1%). The prevalence of disability increased with age and doubled with every 5-year increment in age. Prevalence was higher in women than in men, especially among those aged 85 years or older. With respect to the cause of functional disability, dementia accounted for 23.5%, stroke for 24.7%, orthopedic disease for 12.9%, and other disease for 38.9% of cases in men; in women, the respective values were 35.8%, 9.3%, 31.0%, and 23.9%. Regarding age, dementia was the most frequent cause of disability in subjects aged 75 years or older, whereas stroke was most common in subjects aged 65 to 74 years. Approximately two-thirds of cases of total dependence were attributed to dementia in both sexes, whereas the main cause of slight or moderate/severe dependence was stroke in men and orthopedic disease in women. Among participants with total dependence, 94.8% resided in a hospital or health care facility., Conclusions: Our findings indicate that functional disability is common among Japanese elderly adults and that its major cause is stroke in men and dementia in women.

Objective: Few studies have examined the association between natriuretic peptides and the incidence of cardiovascular disease (CVD) in Asian populations., Methods and Results: A total of 3104 community-dwelling Japanese individuals aged ≥40 years without history of CVD were followed up for 5 years. A total of 127 CVD events were identified. The age- and sex-adjusted incidence of CVD increased with increasing N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (<55, 55-124, 125-399, and ≥400 pg/mL) at baseline and was significantly higher even in subjects with a modest increase. This association remained robust even after adjustment for other potential risk factors (55-124 pg/mL: multivariate-adjusted hazard ratio=1.85 [95% CI 1.07-3.18], P=0.03; 125-399 pg/mL: 2.98 [95% CI 1.65-5.39], P<0.001; ≥400 pg/mL: 4.54 [95% CI 2.22-9.29], P<0.001). The multivariate-adjusted hazard ratios for the development of total CVD and its subtypes, coronary heart disease and stroke, were significantly increased by a 1 SD increment of the log NT-proBNP concentrations and were nearly equal among CVD subtypes. Similar findings were observed for stroke subtypes of ischemic stroke and intracerebral hemorrhage but not subarachnoid hemorrhage. The effects of the 1 SD increment in log NT-proBNP values were comparable in subjects with and without other cardiovascular risk factors, except for sex. The area under the receiver operating characteristic curve was significantly (P=0.006) increased by adding NT-proBNP values to the model including other potential risk factors., Conclusions: Elevated NT-proBNP levels were shown to be a significant risk factor for the development of CVD and its subtypes in a general Japanese population, independently of other cardiovascular risk factors.