中込 敦士

There is inconsistent evidence on the association between community-level social capital and the health or well-being of older adults. This study examined the association between community-level social capital and multidimensional health and well-being outcomes using an outcome-wide approach. We used data from the Japan Gerontological Evaluation Study, a nationwide cohort study of Japanese older adults (analytic samples: 47,227 for outcomes obtained from the long-term care insurance registry and 34,183 for other outcomes). We assessed three aspects of school-district-level community social capital in 2016 (civic participation, social cohesion, and reciprocity) and 41 subsequent health and well-being outcomes through 2019. We performed either a modified multilevel Poisson regression or a multilevel logistic regression analysis. We adjusted for pre-baseline characteristics, prior outcome values, and individual-level social capital from the 2013 wave. Even after Bonferroni correction, we found that community-level social capital was associated with some subsequent social well-being and physical/cognitive health. For example, community-level reciprocity was associated with a higher prevalence of taking a social role (Prevalence ratio [PR] = 1.03, 95% confidence interval [CI] = 1.02, 1.04) and undergoing health screening (PR = 1.03, 95% CI: 1.01, 1.04). There was modest evidence that community-level civic participation was associated with a higher competency of intellectual activity (PR = 1.01, 95% CI: 1.01, 1.02) and community-level social cohesion was associated with a reduced onset of functional disability (PR = 0.94, 95% CI: 0.90, 0.98). Community-level social capital may promote social well-being and some physical/cognitive health outcomes.

IMPORTANCE: There are limited data on whether the vulnerabilities and impacts of social isolation vary across populations. OBJECTIVE: To explore the association between social isolation and mortality due to all causes, cardiovascular diseases (CVD), and malignant neoplasms focusing on heterogeneity by sociodemographic factors. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a moderator-wide approach to examine the heterogeneity in the association of social isolation with all-cause, CVD, and malignant neoplasm mortality using baseline data from the Japan Gerontological Evaluation Study in 2010 and 2011. Eligible participants were adults aged 65 years or older without heart disease, stroke, cancer, or impaired activity of daily living across 12 Japanese municipalities. Follow-up continued until December 31, 2017, identifying 6-year all-cause, cardiovascular disease (CVD), and malignant neoplasm mortality. Logistic regression assessed effect modification by age, gender, education, income, population density, marital status, and employment on mortality associations. Data analysis was performed from September 13, 2023, to March 17, 2024. EXPOSURE: Social isolation, determined by a 3-item scale (scores of 2 or 3 indicating isolation) was the primary exposure variable. MAIN OUTCOMES AND MEASURES: Six-year all-cause, CVD, and malignant neoplasms mortality. RESULTS: This study included 37 604 older adults, with a mean (SD) age of 73.5 (5.9) years (21 073 women [56.0%]). A total of 10 094 participants (26.8%) were classified as experiencing social isolation. Social isolation was associated with increased all-cause (odds ratio [OR], 1.20 [95% CI, 1.09-1.32]), CVD (OR, 1.22 [95% CI, 0.98-1.52]), and malignant neoplasm mortality (OR, 1.14 [95% CI, 1.01-1.28]). Stratified analysis showed associations of social isolation with all-cause and malignant neoplasm mortality among people with high income (highest tertile all cause: OR, 1.27 [95% CI, 1.06-1.53]; malignant neoplasm: OR, 1.27 [95% CI, 1.02-1.60]), living in areas with high population density (highest tertile all cause: OR, 1.47 [95% CI, 1.26-1.72]; malignant neoplasm: OR, 1.38 [95% CI, 1.11-1.70]), not married (all cause: OR, 1.33 [95% CI, 1.15-1.53]; malignant neoplasm: OR, 1.25 [95% CI, 1.02-1.52]), and retirees (all cause: OR, 1.27 [95% CI, 1.14-1.43]; malignant neoplasm: OR, 1.27 [95% CI, 1.10-1.48]). Formal testing for effect modification indicated modification by population density and employment for all-cause mortality and by household income and employment for neoplasm mortality. CONCLUSIONS AND RELEVANCE: Social isolation was associated with increased risks of all-cause, CVD, and malignant neoplasm mortality, with associations varying across populations. This study fills an important gap in research on social isolation, emphasizing its varied associations across demographic and socioeconomic groups.

Internet use influences social interactions in society. However, there is no consensus on whether and what kind of Internet use increases face-to-face communication (FFC). This study investigated the mode of Internet use that increases FFC among older adults after three years. Participants were 8734 adults aged 65 or older who responded to the Japan Gerontological Evaluation Study (JAGES) surveys in 2016 and 2019. The exposures were the purposes of Internet use in 2016. The outcome was the frequency of FFC with friends or acquaintances in 2019. The confounders included 13 demographic, socioeconomic, and psychological variables. We performed modified Poisson regression analyses and found that Internet use for communication in 2016 increased FFC in 2019, especially for low-frequency FFC in 2016. Internet-based non-FFC may help promote FFC and prevent social isolation among older adults who are less likely to interact with others.

Abstract Objective Living a happy life is an essential issue for old adults. However, how eating with others contributes to happiness and whether this association is different by living arrangements or not is unknown. The current study examined the relationship between the frequency of eating with others and happiness among older adults according to their living arrangements using 3‐year longitudinal data. Methods The analyzed sample comprised 18,727 people (10,920 males and 7807 females) with low happiness (0–7 points on score of 0–10 points) from Japan Gerontological Evaluation Study (JAGES) in 2016. Our exposure was the frequency of eating with others: rarely, a few times a year, a few times a month, and a few times a week or more. We performed Modified Poisson Regression to examine the association between the frequency of eating with others and high happiness (8–10 points) in 2019 stratified by living arrangement (living alone/with others). Results A total of 4352 (23.2%) people showed high happiness in 2019. After adjusting for age, sex, marital status, education, household income, social participation, illnesses under treatment, and depressive symptoms in 2016, the cumulative incidence ratio (CIR) for high happiness in 2019 among people living alone was more significant, that is, 1.28 (95% confidence intervals: 0.88–1.87), 1.50 (1.05–2.14), and 1.82 (1.26–2.63), than 1.28 (1.11–1.48), 1.30 (1.12–1.50), and 1.33 (1.16–1.52) among people living with others for those who ate with others a few times a year, a few times a month, and a few times a week or more compared to those who rarely ate with others, respectively. The interaction between the frequency of eating with others and living arrangements was statistically significant. The trend test showed that higher frequency of eating with others was significantly associated with high happiness. Conclusions Eating with others was associated with improved happiness among older adults, with such an association being stronger among people living alone.

OBJECTIVES: Poor medication adherence among older adults is a global concern as it causes adverse drug interactions and inappropriate dosing. This study aimed to assess the association between family pharmacy and medication adherence among older adults. METHODS: The Japan Gerontological Evaluation Study was a cross-sectional study of 18,792 people aged ≥65 years living in 61 municipalities in 25 prefectures who participated in a survey conducted in 2019 and did not require long-term care. Self-reported questionnaires were administered to evaluate whether the participants "always received medicines from the same pharmacy" and whether they had unused medicines. Modified Poisson regression was used to examine the association after adjusting for confounders. RESULTS: Unused medicines were present in 89.9% of the "have group" (individuals who always received their medicines from the same pharmacy). This group had a lower prevalence of unused medicines (prevalence ratio = 0.87, 95% confidence interval: 0.82-0.92) than the "none group" (individuals who did not always receive their medicines from the same pharmacy). In the stratified analysis by education level, the prevalence of unused medicines was lower among those with low levels of education (≤9 years: 0.82, 0.71-0.96; 10-12 years: 0.81, 0.74-0.88). DISCUSSION: Older adults who "always received medicines from the same pharmacy" had a lower prevalence of unused medicines, especially those with low levels of education. Thus, "always receiving medicines from the same pharmacy" may be effective in reducing the proportion of unused medicines and improving medication adherence.

目的:高齢者の移動支援として試行導入したグリーンスローモビリティ(以下,グリスロ)利用による外出,社会的行動,ポジティブ感情を感じる機会の主観的変化を明らかにした.方法:2市3地域で8週間グリスロを導入し,導入前後の自記式質問紙調査に回答した65歳以上の高齢者599人を分析対象とした.対象者をグリスロ利用群と非利用群の2群に分け,導入後の外出(行動範囲など),社会的行動(地域活動に参加など),ポジティブ感情(気持ちが明るくなるなど)の変化を評価した.ポアソン回帰分析を実施し,累積発生比と95%信頼区間,P値をそれぞれ求めた.P値はボンフェローニ法により補正した(有意水準:P=0.0042).結果:グリスロ利用群は非利用群と比較して外出,社会的行動,ポジティブ感情の機会が2～5割,累積発生比で1.74～5.21倍と有意に高かった.結論:グリスロには移動支援にとどまらず,"動く"通いの場のような心理社会的な変化もあり,健康に資する可能性が示唆された.(著者抄録)

The effect of prehospital factors on favorable neurological outcomes remains unclear in patients with witnessed out-of-hospital cardiac arrest (OHCA) and a shockable rhythm. We developed a decision tree model for these patients by using prehospital factors. Using a nationwide OHCA registry database between 2005 and 2020, we retrospectively analyzed a cohort of 1,930,273 patients, of whom 86,495 with witnessed OHCA and an initial shockable rhythm were included. The primary endpoint was defined as favorable neurological survival (cerebral performance category score of 1 or 2 at 1 month). A decision tree model was developed from randomly selected 77,845 patients (development cohort) and validated in 8650 patients (validation cohort). In the development cohort, the presence of prehospital return of spontaneous circulation was the best predictor of favorable neurological survival, followed by the absence of adrenaline administration and age. The patients were categorized into 9 groups with probabilities of favorable neurological survival ranging from 5.7 to 70.8% (areas under the receiver operating characteristic curve of 0.851 and 0.844 in the development and validation cohorts, respectively). Our model is potentially helpful in stratifying the probability of favorable neurological survival in patients with witnessed OHCA and an initial shockable rhythm.

目的 健康寿命延伸プランの主要3分野の1つに,高齢者のフレイル対策が掲げられ,その1つとして社会参加の活用が期待されている。しかし,これまでの先行研究では,社会参加の種類や数とフレイル発症との関連を縦断的に検証した報告はない。本研究では,大規模縦断データを用い,社会参加の種類や数とフレイル発生との関連について検証することを目的とした。方法 日本老年学的評価研究(Japan Gerontological Evaluation Study:JAGES)の2016年度と2019年度のパネル調査データを用いた縦断研究である。2016年度(ベースライン時点)と2019年度(追跡時)のJAGES調査に回答した高齢者から,ベースライン時点の日常生活動作の非自立者と無回答者,フレイル(基本チェックリスト8点以上/25点)とフレイル判定不能者などを除いた,28市町59,545人を分析対象とした。目的変数は追跡時のフレイル発症とし,説明変数はベースライン時点の9種類の社会参加の種類と数を用いた。調整変数には,ベースライン時点の性,年齢,等価所得,教育歴,婚姻,家族構成,就労,プレフレイル(基本チェックリスト4～7点/25点)の有無,喫煙,飲酒,都市度の11変数を用いた。多重代入法により欠損値を補完し,ポアソン回帰分析を用いて社会参加とフレイル発症との関連を検証した。結果 追跡時のフレイル発症は6,431人(10.8%)であった。多重代入法後(最小64,212人,最大64,287人)の分析の結果,老人クラブを除く8種類の社会参加先である介護予防(Risk Ratio:0.91),収入のある仕事(0.90),ボランティア(0.87),自治会(0.87),学習・教養(0.87),特技・経験の伝達(0.85),趣味(0.81),スポーツ(0.80)で,フレイル発症リスクが有意に低かった。さらに,社会参加数が多い人ほどフレイル発症リスクが有意に低かった(P for trend<0.001)。結論 社会参加とフレイル発症リスクとの関連を検証した結果,ベースライン時点で8種類の社会参加をしている人,社会参加数が多い人ほど3年後のフレイル発症リスクが低かった。健康寿命延伸に向けたフレイル対策の一環とし,社会参加の促進が有用であることが示唆された。(著者抄録)

Abstract Background and Objectives Evidence remains inadequate regarding the benefits of participation in community gathering places, which is Japan’s primary strategy for preventing functional disability in older adults, in other domains of health and well-being. This longitudinal study examined the associations of participation in community gathering places with an array of subsequent health and well-being outcomes among older adults. Research Design and Methods We used three-wave data (2013, 2016, and 2019) from Japan Gerontological Evaluation Study (n = 5,879 or 4,232 depending on the outcome). Our exposure was participation in community gathering places in 2016. We assessed 34 health/well-being outcomes in 2019 across six domains. We adjusted for pre-baseline covariates including prior outcome values in 2013. Results Compared with nonparticipation, participation in community gathering places was associated with some outcomes in the following three domains: physical/cognitive health (better higher-level functional capacity), social well-being (more frequent participation in hobby groups, senior citizens clubs, learning or cultural groups, and seeing more friends within a month), and pro-social/altruistic behaviors (more frequent participation in volunteering) (After Bonferroni correction as p &amp;lt; 0.0015, 0.05/34). Discussion and Implications Evidence was mixed and more modest for the outcomes in three other domains, mental health, psychological well-being, and health behaviors. Promoting participation in community gathering places may not only fulfill its original goal (i.e., preventing functional disability) but also enhance other domains of human well-being, potentially by increasing social interactions.

PURPOSE: A growing body of evidence suggests that oral health is associated with a wide range of health outcomes; however, opinions tend to vary because of inconsistent findings. This study aimed to simultaneously examine the association between oral health status and multiple health and well-being indicators using outcome-wide epidemiology. METHODS: Data were obtained from the Japan Gerontological Evaluation Study. Oral health status was categorized as: ≥20 teeth, 10-19 teeth with dental prosthesis, 0-9 teeth with prosthesis, 10-19 teeth without prosthesis, and 0-9 teeth without prosthesis. We examined the associations between oral health status in 2013 and 35 health and well-being outcomes in 2019, including physical/cognitive health, psychological distress, subjective health, social well-being, prosocial/altruistic behaviors, and health behaviors, using two databases (n=32,827 and 15,905). RESULTS: Compared to individuals with ≥20 teeth, those with <20 teeth had a 10-33% higher risk of mortality and a 7-10% higher risk of functional disability six years later. Additionally, individuals with fewer than 20 teeth tended to go out less frequently and eat fewer vegetables and fruits. Furthermore, individuals with 0-9 teeth without a prosthesis were more likely to have severe functional disability (risk ratio (RR):1.17, 95% confidence interval (CI):1.05-1.31), engage in fewer intellectual activities (standardized difference: 0.17, 95% CI: 0.10-0.24), and feel more hopeless (RR: 1.21, 95% CI: 1.04-1.41). CONCLUSIONS: The prevention of tooth loss and prosthodontic treatment may be associated with reduced mortality and functional disability, as well as maintenance of intellectual ability, frequency of going out, and improvements in dietary lifestyle.

BACKGROUND: Although remote communication technologies have been widely used to maintain connections with others against interpersonal contact restrictions and exacerbated loneliness during the COVID-19 pandemic, it is unclear whether and what types of remote communication technologies are effective in mitigating loneliness. OBJECTIVE: This study aimed to investigate the association between remote communication and loneliness when face-to-face meetings with others were strongly prohibited and whether this association varied across types of communication tools, age, and gender. METHODS: We used cross-sectional data from the Japan COVID-19 and Society Internet Survey conducted from August to September 2020. From registered panelists of the research agency, 28,000 randomly sampled participants completed the survey on the website. We created 2 study cohorts who stopped meeting with family members living apart and friends during the pandemic. We categorized whether participants had technology-based remote communication (voice calling, text messaging, and video calling) with family and friends. Loneliness was assessed using the 3-item University of California, Los Angeles Loneliness Scale. We used a modified Poisson regression model to investigate the association between loneliness and remote communication with family members living apart or friends. We also conducted subgroup analyses based on age and gender. RESULTS: A total of 4483 participants stopped meeting with family members living apart, and 6783 participants stopped meeting with friends during the COVID-19 pandemic. Remote communication with family members living apart did not show an association with loneliness, whereas remote communication with friends was associated with a low prevalence of loneliness (family: adjusted prevalence ratio [aPR]=0.89, 95% CI 0.74-1.08; P=.24 and friends: aPR=0.82, 95% CI 0.73-0.91; P<.001). From analyses by tools, voice calling was associated with low loneliness (family: aPR=0.88, 95% CI 0.78-0.98; P=.03 and friends: aPR=0.87, 95% CI 0.80-0.95; P=.003). Similarly, text messaging was associated with low loneliness (family: aPR=0.82, 95% CI 0.69-0.97; P=.02 and friends: aPR=0.81, 95% CI 0.73-0.89; P<.001). However, we did not find an association between video calling and loneliness (family: aPR=0.88, 95% CI 0.75-1.02; P=.09 and friends: aPR=0.94, 95% CI 0.85-1.04; P=.25). Text messaging with friends was associated with low loneliness regardless of age, whereas voice calling with family or friends was associated with low loneliness only among participants aged ≥65 years. An association between remote communication with friends and low loneliness was found regardless of the type of remote communication tool among men, whereas it was found only for text messaging with friends among women. CONCLUSIONS: In this cross-sectional study of adults in Japan, remote communication, especially via voice calling and text messaging, was associated with low loneliness. Promoting remote communication may reduce loneliness when face-to-face contact is restricted, which should be the subject of future research.

Objective Mutsuzawa town, Chiba Prefecture, relocated a "health-supportive" roadside station in 2019. The underlying hypothesis is that older people who use the roadside station will have better self-rated health than those who do not use it. We aimed to verify whether roadside station use was associated with a decrease in poor self-rated health.Method This was a longitudinal study that compared and evaluated the roadside station use and non-use groups using three-wave panel data before and after relocation of the roadside station in September 2019. To obtain three-wave panel data, self-administered questionnaires were mailed three times: in July 2018 (FY 2018) before the station was relocated and in November 2020 (FY 2020) and January 2022 (FY 2021) after the relocation in 2019. The dependent variable was poor self-rated health in FY 2021, and the independent variable was use of the roadside station as of FY 2020. Covariates included basic characteristics from FY 2018, as well as going out, social participation, and interacting on social networks in FY 2018 and FY 2020. A multivariate analysis was conducted using multiple imputation to complete missing values for the Crude model, which included the basic attributes of FY 2018 (Model 1); going out, social participation, and interacting on social networks in FY 2018 (Model 2); and going out, social participation, and interacting on social networks in FY 2020 (Model 3). The cumulative incidence rate ratio (CIRR), 95% confidence intervals, and P-values were calculated using a modified Poisson regression analysis for each model.Results Of the 576 participants, 344 (59.8%) were roadside station users. The multivariate analysis adjusted for basic attributes revealed that the number of people with poor self-rated health in the user group was significantly lower than that in the non-user group, with a CIRR of 0.67 (95% confidence interval: 0.45-0.99, P=0.043). However, the adjusted model showed a CIRR of 0.71 (95% confidence interval: 0.48-1.06, P=0.096) for going out, social participation, and interacting on social networks in FY2020 after the roadside station opened.Conclusion Findings of this study revealed that, after adjusting for confounding factors prior to relocation of the roadside station, the number of people with poor self-rated health decreased in the user group. Thus, such commercial facilities as roadside stations, which give users an opportunity to go out and meet people, can provide a "naturally healthy" environment.

Objective In Japan, measures to prevent frailty among older adults have been implemented. Promotion of social participation is a key measure, but few longitudinal studies have examined the relationship between the types and number of social participation and frailty onset. In this study, we aimed to clarify the relationship between the types and number of social participation and frailty onset using longitudinal data from a large sample of older adults in municipalities in Japan.Methods We used the 2016 and 2019 panel survey data from the Japan Gerontological Evaluation Study (JAGES). The analysis included 59,545 individuals from 28 municipalities who responded to the JAGES survey in both 2016 (at baseline) and 2019 (at follow-up). We excluded individuals who were dependent on activities of daily living at baseline and non-responders, and those who were frail or with no information about frailty. The dependent variable was frailty onset (≥8 out of 25 points on the basic checklist) at follow-up, and the independent variables were the types and number of types of social participation at baseline. We included 11 variables as potential confounders. We used multiple imputations to complete the missing values and used modified Poisson regression to examine the association between social participation and risk of frailty onset.Results Of the 59,545 participants, 6,431 (10.8%) were frail onset at follow-up. After multiple imputations (minimum 64,212, maximum 64,287), the risk of frailty onset at follow-up was lower for eight types of social participation, excluding senior citizens' clubs, (nursing care [risk ratio; 0.91], paid work [0.90], volunteer groups [0.87], neighborhood associations [0.87], learning or cultural groups [0.87], activities intended to teach skills or pass experiences to others [0.85], hobby groups [0.81], and sports groups or clubs [0.80]; P<0.05), than no social participation. Additionally, individuals who participated in more types of social participation were at a lower risk of frailty than those with no social participation (P for trend <0.001).Conclusions The risk of frailty onset was lower among individuals who participated in eight types of social participation at baseline and among those who participated in more types of social participation than those with no social participation. The results suggest that social participation is a useful measure to prevent frailty for extending healthy life expectancy.

Hypertension is a leading cause of cardiovascular disease and despite established strategies to lower blood pressure, the control of hypertension remains poor. This is true even in high-income countries with well-established welfare and medical systems. Among the social factors associated with hypertension (i.e., social determinants of hypertension, SDHT), individual socioeconomic status (SES), including education, income, and occupation, can be crucial for hypertension management (prevalence, awareness, treatment, and control). This article reviews the findings of recently published studies that examined the association between SES and hypertension management in high-income countries. It also discusses social prescribing, which targets social isolation and loneliness as modifiable SDHT to improve hypertension management.

There is a growing, but inconclusive, evidence on the beneficial influence of the Internet on the health/wellbeing of older people. This study aims to examine outcomes-wide associations between frequency of internet use and subsequent health/well-being among older individuals. We used the three-wave data (2013, 2016, and 2019) from the Japan Gerontological Evaluation Study. Our exposure was frequency of internet use (not at all/ use a few times a month/use a few times a week/use almost every day) in 2016. We assessed 34 health/wellbeing outcomes in 2019 across six dimensions. Pre-exposure characteristics and prior outcome levels in 2013 were adjusted. We included 5879 respondents for 4 outcomes (death, dementia, and functional disability) and 4232 respondents for 30 other outcomes. Using the Internet almost every day (vs. not using at all) in 2016 was associated with some outcomes in 2019 in three dimensions: physical/cognitive health (better instrumental activities of daily living), social well-being (more frequent participation in sports groups, meeting friends more frequently, and seeing more friends within a month), and health behaviors (receiving health screening) (p < 0.05 for these associations after Bonferroni correction). It was not associated with any outcomes of three other dimensions: psychological distress, subjective well-being, or pro-social/altruistic behaviors.

BACKGROUND: In-person religious service attendance has been linked to favorable health and well-being outcomes. However, little research has examined whether online religious participation improves these outcomes, especially when in-person attendance is suspended. METHODS: Using longitudinal data of 8951 UK adults, this study prospectively examined the association between frequency of online religious participation during the stringent lockdown in the UK (23 March -13 May 2020) and 21 indicators of psychological well-being, social well-being, pro-social/altruistic behaviors, psychological distress, and health behaviors. All analyses adjusted for baseline socio-demographic characteristics, pre-pandemic in-person religious service attendance, and prior values of the outcome variables whenever data were available. Bonferroni correction was used to correct for multiple testing. RESULTS: Individuals with online religious participation of ≥1/week (v. those with no participation at all) during the lockdown had a lower prevalence of thoughts of self-harm in week 20 (odds ratio 0.24; 95% CI 0.09-0.62). Online religious participation of <1/week (v. no participation) was associated with higher life satisfaction (standardized β = 0.25; 0.11-0.39) and happiness (standardized β = 0.25; 0.08-0.42). However, there was little evidence for the associations between online religious participation and all other outcomes (e.g. depressive symptoms and anxiety). CONCLUSIONS: There was evidence that online religious participation during the lockdown was associated with some subsequent health and well-being outcomes. Future studies should examine mechanisms underlying the inconsistent results for online v. in-person religious service attendance and also use data from non-pandemic situations.

Evidence on the association between internet usage and incidence of depression remains mixed. We examined the associations between different categories of internet usage and developing clinical depression. We used data from the 2013 and 2016 waves of the Japan Gerontological Evaluation Study (JAGES) comprising 12,333 physically and cognitively independent adults aged ≥65 years. Participants were engaged in seven categories of internet usage: communication with friends/family, social media, information collection about health/medicine, searching for medical facilities, purchase of drugs and vitamins, shopping, and banking. We found that internet use for communication had a protective influence on the probability of developing clinical depression defined as the Geriatric Depression Scale scores ≥5 or self-reported diagnosed depression. Our findings support the role of online communication with friends/family in preventing clinical depression among older people. Online communication could be particularly useful in the COVID-19 crisis because many families are geographically dispersed and/or socially distanced.

General health checks to detect cardiovascular risk factors form part of routine health care in many countries. Cardiovascular disease and dementia share a number of risk factors; however it remains unclear whether general health checks can reduce the incidence of dementia. We used longitudinal data from the Japan Gerontological Evaluation Study with up to 6.4 years follow-up (from 2010 to 2016). A total of 31,012 disability-free adults aged 65-74 were included. The outcome variable was dementia onset certified under the national long-term care insurance system. The treatment variable was defined as having health checks within the past 12 months prior to the baseline survey in 2010. After multiple imputation, we performed propensity score matching (PSM) to exclude off-support individuals who were the least likely to have health checks. We also performed inverse probability treatment weighting (IPTW) to estimate the effect of the treatment if everyone within the population was compliant to health checks. The hazard ratios for dementia onset among those reporting health checks within the previous year was 0.89 (95% confidence interval (CI): 0.78, 1.02) in the PSM analysis and 0.84 (95% CI: 0.75, 0.95) in the IPTW analysis. We then estimated the effect of health checks on 5-year incident dementia. The 5-year cumulative incidence difference based on the PSM analysis was -0.0046 (95%CI: -0.0101, 0.0009), while that based on the IPTW analysis was -0.0046 (95%CI, -0.0090, -0.0002). The PSM and IPTW approaches yielded similar findings that the incidence of dementia was lower among people having health checks.

OBJECTIVES: Widowhood is associated with increased risks of depression in the surviving spouse. We examined whether an increase in individual-level social capital mitigates the adverse impact of widowhood on depressive symptoms. METHODS: We used data from the 2013/2016 waves of the Japan Gerontological Evaluation Study of functionally independent adults aged 65 years or older (men: n = 20,853; women: n =16,858). Fixed-effects regression was applied to examine the potential buffering effects of changes in social capital on changes in depressive symptoms following widowhood among married people living with their spouse and/or others at baseline. RESULTS: Widowhood had a deleterious impact on depressive symptoms particularly among men who ended up living alone following their spouse's death. Fixed-effects models revealed that an increase in informal socializing and social participation might buffer the effects of spousal bereavement on depressive symptoms among men who became widowed during the first two years of follow-up and ended up living alone. DISCUSSION: An increase in structural social capital may mitigate the impact of spousal bereavement on depressive symptoms. However, the associations vary by gender, living arrangement, and time since widowhood. Intensive efforts should be directed toward connecting the vulnerable group, widowed men living alone, to sources of social capital.

The management of acute decompensated heart failure often requires intensive care. However, the effects of early intensive care unit/coronary care unit admission on activities of daily living (ADL) in acute decompensated heart failure patients have not been precisely evaluated. Thus, we retrospectively assessed the association between early intensive care unit admission and post-discharge ADL performance in these patients. Acute decompensated heart failure patients (New York Heart Association I-III) admitted on emergency between April 1, 2014, and December 31, 2018, were selected from the Diagnosis Procedure Combination database and divided into intensive care unit/coronary care unit (ICU) and general ward (GW) groups according to the hospitalization type on admission day 1. The propensity score was calculated to create matched cohorts where admission style (intensive care unit/coronary care unit admission) was independent of measured baseline confounding factors, including ADL at admission. The primary outcome was ADL performance level at discharge (post-ADL) defined according to the Barthel index. Secondary outcomes included length of stay and total hospitalization cost (expense). Overall, 12231 patients were eligible, and propensity score matching created 2985 pairs. After matching, post-ADL was significantly higher in the ICU group than in the GW group [mean (standard deviation), GW vs. ICU: 71.5 (35.3) vs. 78.2 (31.2) points, P<0.001; mean difference: 6.7 (95% confidence interval, 5.1-8.4) points]. After matching, length of stay was significantly shorter and expenses were significantly higher in the ICU group than in the GW group. Stratified analysis showed that the patients with low ADL at admission (Barthel index score <60) were the most benefited from early intensive care unit/coronary care unit admission. Thus, early intensive care unit/coronary care unit admission was associated with improved post-ADL in patients with emergency acute decompensated heart failure admission.

The underlying mechanism for deterioration in cardiometabolic health after major natural disasters is unknown. We leveraged natural experiment data stemming from the 2011 Great East Japan Earthquake and Tsunami (n = 1165) to examine whether specific types of post-disaster accommodations explain the association between disaster-related property damage and objectively measured cardiometabolic profiles of older disaster survivors. Causal mediation analysis showed that relocation to trailer-style temporary shelters largely mediated the associations between home loss and unhealthy changes in anthropometric measures (72.6% of 0.65 kg/m2 for body mass index and 62.3% of 3.89 cm for waist circumference), but it did not mediate the associations with serum lipid measures. This study demonstrates that there are outcome-specific pathways linking disaster damage and health of survivors.

Widowhood and living alone are linked to increased risk of depression. We examined prospectively whether community-level social capital can mitigate the adverse impact of widowhood and living alone on depressive symptoms. We used data of the Japan Gerontological Evaluation Study of functionally independent adults aged 65 years or older. Three waves of surveys were collected in 2010, 2013 and 2016. We conducted gender-stratified multilevel linear regression to examine the moderating effects of community-level social capital on depressive symptoms (as assessed by the 15-point Geriatric Depression Scale) associated with widowhood and living alone. Widowhood in the past 12 months in combination with living alone was associated with a marked worsening in depressive symptoms among men (beta coefficient = 1.67; 95% confidence interval: 1.38, 1.95). Community-level civic participation, but not social cohesion or reciprocity, was associated with lower depressive symptoms in men and women. In addition, community-level civic participation moderated the association between depressive symptoms and recent widowhood/living alone among men (coefficient per 1 standard deviation = -0.30; 95% confidence interval: -0.59, -0.02). We found no significant effect modification of community-level social capital on depressive symptoms associated with widowhood and living alone among women. Communities with greater civic participation appear to mitigate the onset of depressive symptoms among recently widowed men living alone. Promotion of community activities might be an effective community-level intervention to promote mental health in this vulnerable group.

AIMS: To investigate the predictive capability of insulin resistance surrogate markers for insulin resistance and arterial stiffness based on sex. METHODS: We assessed the association of triglyceride glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), visceral adiposity index (VAI), and lipid accumulation product (LAP) with homeostasis model assessment-insulin resistance (HOMA-IR) and brachial-ankle pulse wave velocity (baPWV) in both sexes. RESULTS: A total of 1720 men and 1098 women were evaluated. HOMA-IR showed good correlation with the TyG index (men: r = 0.47, women: r = 0.45), TG/HDL-C (men: r = 0.45, women: r = 0.41), VAI (men: r = 0.51, women: r = 0.48), and LAP (men: r = 0.55, women r = 0.49) (all p-values < 0.001). These markers positively correlated with increased baPWV in both sexes. The standardized partial regression coefficients were 0.11 and 0.14 for the TyG index, 0.13 and 0.16 for TG/HDL-C, 0.14 and 0.19 for VAI, and 0.12 and 0.17 for LAP in men and women, respectively (all p-values < 0.01; all p-values for sex interaction < 0.05). CONCLUSIONS: All insulin surrogate markers showed good correlation with HOMA-IR in both sexes. These indices were also associated with increased baPWV and the associations were stronger in women than in men.

Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mmHg and diastolic BP (DBP) <90 mmHg, is a common type of hypertension among young men. This study aimed to investigate the clinical characteristics, central blood pressure, and arterial stiffness of young and middle-aged Japanese individuals with ISH. A total of 432 male participants, aged 18-49 years, were classified into six subgroups: optimal BP (SBP <120 mmHg and DBP <80 mmHg), high-normal BP (SBP 120-129 mmHg and DBP <80 mmHg), high-BP (SBP 130-139 mmHg and/or DBP 80-89 mmHg), ISH (SBP ≥140 mmHg and DBP <90 mmHg), isolated diastolic hypertension (IDH) (SBP <140 mmHg and DBP ≥90 mmHg), and systolic and diastolic hypertension (SDH) (SBP ≥140 mmHg and DBP ≥90 mmHg). Participants with ISH had a greater body mass index (BMI) and waist circumference than the optimal BP participants but were more likely to be physically active than the IDH and SDH participants. The central SBP of the ISH subgroup was higher than that of the optimal/high-normal/high-BP subgroups and lower than that of the SDH subgroup. The carotid-femoral pulse wave velocity (cfPWV) of the ISH subgroup was higher than that of the optimal and high-normal BP subgroups and lower than that of the SDH subgroup after adjusting for age, heart rate, BMI, and physical activity. These differences disappeared after further adjustment for central mean arterial pressure. In conclusion, the central SBP of Japanese men with ISH was greater than that of Japanese men with optimal/high-normal/high-BP, but the progression of arterial stiffness was unclear.

BACKGROUND: Although current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI). METHODS: Using a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days. RESULTS: The CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67). CONCLUSIONS: The use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI.

AIM: One-hour post-load plasma glucose (1h-PG) during an oral glucose tolerance test and smoking are associated with arterial stiffness. However, it remains unknown whether there are synergistic effects of these two factors on arterial stiffness. This study aimed to investigate the interaction between 1h-PG and smoking in relation to brachial-ankle pulse wave velocity (baPWV) in young men with normal glucose tolerance (NGT). METHODS: The study included 25-, 30-, 35-, 40-, and 45-year-old non-industrial male workers (n=2189) who underwent a detailed health check-up. Normotensive participants with NGT and taking no medication were included. RESULTS: A univariate linear regression analysis showed that 1h-PG correlated with baPWV (r=0.13, p＜0.001), but the correlation was not significant in the multivariate analysis (β=0.02, p=0.24). However, we found a significant interaction between 1h-PG levels and smoking status in relation to baPWV (p=0.048). Therefore, further analyses were conducted in nonsmokers and smokers. A multivariate linear regression analysis revealed that 1h-PG significantly correlated with baPWV in smokers (β=0.11, p=0.02), but not in nonsmokers (β=0.01, p=0.79). The correlation remained significant even after adjustment for the number of cigarettes smoked per day (β=0.096, p=0.048) or the Brinkman index (β=0.097, p=0.043). CONCLUSION: A significant interaction between 1h-PG and smoking in relation to baPWV was found in apparently healthy men younger than 50 years old.

BACKGROUND: Many factors are associated with hypertension development. We focused on social participation as an aspect of social capital and investigated the contextual relationship between community-level social participation and hypertension using multilevel regression analyses. METHODS: We used cross-sectional data from the 2016 Japan Gerontological Evaluation Study-a population-based study of functionally independent adults aged 65 years or older. The sample comprised 116,013 participants nested in 818 communities. Hypertension and social capital were defined by questionnaires. Social capital was assessed at both the individual and the community levels in 3 dimensions: civic participation (as an index of social participation), social cohesion, and reciprocity. RESULTS: The prevalence rate of hypertension was 43.7%, and 44.1% of the respondents were involved in civic participation. Community-level civic participation, but not social cohesion or reciprocity, was negatively associated with hypertension in the total population (prevalence ratio (95% confidence interval): 0.98 (0.96-0.99), P = 0.004) and female group (0.97 (0.95-0.99), P = 0.015), and the association neared significance in the male group (0.98 (0.96-1.005), P = 0.13) after adjustment for individual-level social capital dimensions including civic participation, individual-level covariates, and population density as a community-level covariate. The interaction between community-level civic participation and sex in relation to hypertension was significant (P = 0.012). CONCLUSIONS: We found a contextual preventive relationship between community-level civic participation and hypertension. The design of the contextual characteristics of communities by the promotion of social participation may help reduce the prevalence of hypertension in older people.

Augmentation index (AIx) and pulse pressure (PP) amplification can be determined by the SphygmoCor XCEL device in an operator-independent manner. This study aimed to examine its validity against invasive measurements. Simultaneous recordings of central aortic pressure waveforms were performed with oscillometric and high-fidelity invasive methods in 35 patients who underwent coronary arteriography. Brachial blood pressure was also recorded using the two methods. AIx for the aortic pressure waveform was defined as the ratio of augmentation pressure to PP. PP amplification was defined as the ratio of brachial PP to aortic PP. The differences between the invasive and oscillometric measurements were -7.7±12.7% for AIx and 0.17±0.14 for PP amplification (mean±s.d.). Strong correlations between the invasive and oscillometric measurements were found in both indices (AIx: r=0.75; PP amplification: r=0.80; both P<0.001). The Bland-Altman plot showed a proportional bias of PP amplification, but not of AIx (AIx: r=-0.21, P=0.23; PP amplification: r=-0.61; P<0.001). In conclusion, estimated AIx may be reliable considering the high correlation between the invasive and noninvasive values and the lack of proportional bias against invasive assessment. However, a substantial underestimation and a large scatter of estimated AIx were also observed. Further studies using the device to investigate associations with target organ damage or prognoses are needed to clarify its clinical validity.

OBJECTIVE: To investigate the relationship between 1-h post-load plasma glucose, measured during an oral glucose tolerance test, and arterial stiffness, determined by brachial-ankle pulse-wave velocity, in normotensive subjects with normal glucose tolerance. METHODS: Study subjects were non-industrial workers aged 25-55 years ( n = 8381) who underwent a regular health check-up every 5 years. We included only normotensive subjects with normal glucose tolerance based on the American Diabetes Association criteria. Subjects taking medication and having an abnormal ankle-brachial index (⩽1.0 or ⩾1.3) were excluded. The final sample comprised 4970 participants (mean age: 38.8 ± 9.4 years; women: n = 2048). RESULTS: 1-h post-load plasma glucose correlated with brachial-ankle pulse-wave velocity in men ( β = 0.04, p = 0.01), but not women ( β = -0.03, p = 0.13) in multivariate linear regression analysis. We found a significant interaction between 1-h post-load plasma glucose and age in men ( p = 0.04); therefore, a subgroup analysis was performed in each 5-year age group. The correlation between 1-h post-load plasma glucose and brachial-ankle pulse-wave velocity was significant in the 55-year-old age group ( β = 0.12, p = 0.01) and neared significant in 45-year-old ( β = 0.08, p = 0.07) and 50-year-old ( β = 0.09, p = 0.07) age groups. CONCLUSION: Elevated 1-h post-load plasma glucose levels were associated with arterial stiffness in normotensive, middle-aged men with normal glucose tolerance.

Our aim was to assess the discrepancy in the blood pressure amplification (BPA) value defined as the aortic-to-brachial increase in systolic BP (SBP) between invasive and noninvasive brachial cuff-based methods. In 45 patients undergoing cardiac catheterization, BP in the brachial artery and ascending aorta were measured with an invasive catheter and a brachial cuff-based oscillometric device. To calculate aortic SBP, brachial waveforms were calibrated by the brachial systolic and diastolic BP (DBP) (C1 calibration) or by the brachial mean BP and DBP (C2 calibration). C1 calibration underestimated aortic SBP (-17.7 mm Hg (95% confidence interval: -21.9 to -13.5)), whereas C2 calibration generated an approximately accurate aortic SBP (1.8 mm Hg (-2.4 to 5.9)). Regarding brachial SBP, noninvasively measured values were markedly underestimated (22.2 mm Hg (-26.4 to -18.0)), resulting in a slightly low BPA value in C1 calibration (11.9±6.3 mm Hg) and a paradoxical negative BPA value in C2 calibration (-7.6±6.7 mm Hg). Multiple linear regression analysis showed that the cuff-catheter difference of BPA was positively correlated with the cuff-catheter difference of brachial SBP in both calibrations (C1 calibration: β=0.51; C2 calibration: β=0.50; both P<0.01). Although noninvasively measured BPA was associated with invasively measured BPA only in C1 calibration (r=0.33, P=0.03), when using invasively measured brachial SBP instead of a cuff-based measurement, the BPA was well associated with invasively measured BPA in both calibrations (C1 calibration: r=0.57; C2 calibration: r=0.52; both P<0.001). In conclusion, there was a trade-off in accuracy between brachial cuff-based noninvasive aortic SBP and BPA because of the inherent inaccuracies in the cuff-based method. This finding should be fully considered in establishing standardized reference values for aortic BP.

BACKGROUND: Several studies have reported that central systolic blood pressure (SBP) estimation is affected by calibration methods. However, whether central pulsatile indices, namely pulse pressure (PP) and fractional PP (FPP) (defined as PP/mean arterial pressure (MAP)), also depend on calibration methods remains uninvestigated. This study assessed the accuracy and discriminatory ability of these indices for coronary atherosclerosis using 2 calibration methods. METHODS: Post-hoc analysis of a previous cross-sectional study (n = 139) that investigated the association between central pulsatile indices and coronary atherosclerosis. A validated-oscillometric device provided PP and FPP at the brachial artery (bPP and bFPP) and central artery using 2 calibration methods: brachial SBP/diastolic BP (DBP) (cPPsd and cFPPsd) and MAP/DBP (cPPmd and cFPPmd). Accuracy was assessed against invasive measurements (cPPinv and cFPPinv). Multivariate logistic and linear regression analyses were performed to assess the association between pulsatile indices and the presence of coronary artery disease (CAD) and SYNTAX score, respectively. RESULTS: cPPmd and cFPPmd were closer to invasive values than cPPsd (cPPsd: 39.6±12.6; cPPmd: 60.2±20.1; cPPinv: 71.4±22.9). cFPP exhibited similar results (cFPPsd: 0.35±0.09; cFPPmd: 0.55±0.14; cFPPinv: 0.70±0.19). In patients ≥70 years, only cFPPmd was significantly associated with CAD risk (odds ratio: 1.66 (95% confidence interval: 1.05-2.64)). SYNTAX score was significantly correlated with cPPmd, cFPPmd, and bFPP (standardized β: cPPmd 0.39, cFPPmd 0.50, bFPP 0.42, all P < 0.01). No significant association was observed in patients aged <70 years. CONCLUSIONS: Central pulsatile indices calibrated with brachial MAP/DBP were more accurate and discriminatory for coronary atherosclerosis than SBP/DBP calibration.

BACKGROUND: Studies have established the prognostic value of central SBP and pulse pressure (PP). The SphygmoCor XCEL (AtCor Medical, Sydney, Australia) device provides practical central blood pressure (BP) measurement for daily clinical use with its easy-to-use, operator-independent procedure. However, this device has not been validated against invasive measurement. METHOD: Simultaneous oscillometric and high-fidelity invasive measurements of central SBP and PP were compared for 36 patients who underwent coronary arteriography. Invasive measurement of brachial BP was also performed. Oscillometrically measured brachial SBP and DBP were used for calibration. RESULTS: The differences between the invasive and the oscillometric measurements were -4.6 ± 9.9 mmHg for central SBP and -18.5 ± 10.6 mmHg for central PP (mean ± SD). We found strong correlation between the invasive and oscillometric measurements (central SBP and central PP, respectively: r = 0.91 and 0.89; slope, 1.28 and 1.38; both P < 0.001). Although the large slopes of the regression lines indicated a systemic bias toward lower values when measuring in high pressure ranges, the bias was mainly due to calibration error rather than device-specific error because errors of the central measurements correlated well with those of brachial measurements (SBP and PP, respectively: r = 0.80 and 0.77; both P < 0.001). CONCLUSION: The impaired accuracy of central BP measurement was mainly due to calibration-derived, but not device-dependent, bias. Strong correlation between oscillometric and invasive measurements indicates that SphygmoCor XCEL warrants future investigations to determine the clinical validity of this device.

We investigated age-related change in the contribution of stroke volume (SV) to central PP (cPP). Eighty seven adult subjects who were free of vasoactive agents were included. Subjects were divided into three age groups: young (20-39 years, n = 26), middle (40-49 years, n = 29), and old (≥50 years, n = 32). SV was calculated by Doppler echocardiography. Hemodynamic indices were measured using a brachial cuff-based oscillometric method. The brachial and cPP showed a small decline from the young group to the middle group and a greater rise after 50 years old. SV significantly and positively correlated with brachial (r = 0.53, p < 0.01) and cPP (r = 0.57, p < 0.01) in the young group. In the middle group, the association of SV with brachial pulse pressure was significant (r = 0.38, p = 0.04) and that with cPP was bordering significant (r = 0.34, p = 0.07). No significant association was found between SV and PP in the old group. In conclusion, the contribution of SV to cPP decreases with age. Age-related changes in the determinants of cPP should be considered when investigating the clinical value of cPP.

The aim of this study was to investigate the association of aortic pulsatility assessed by a non-invasive brachial cuff-based method with coronary atherosclerosis. In total, 139 patients undergoing coronary angiography were included in this cross-sectional study. Aortic blood pressure (BP) indices were recorded invasively by a fluid-filled catheter and non-invasively by a brachial cuff-based oscillometric device. Fractional pulse pressure (FPP) was defined as pulse pressure (PP)/mean BP and pulsatility index (PI) as PP/diastolic BP. Aortic FPP and PI in coronary artery disease (CAD) patients were significantly higher than in non-CAD patients in both invasive and non-invasive methods. Multivariate logistic regression analysis demonstrated that non-invasively measured aortic FPP and PI were associated with CAD risk in patients aged ≥70 years [aortic FPP per 0.1 odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.05-2.64; aortic PI per 0.1 OR =1.39, 95% CI 1.02-1.88; all p < 0.05], but were not associated with CAD risk in patients aged <70 years. In linear regression analysis, non-invasively measured aortic FPP and PI correlated with SYNTAX and Gensini scores only in patients aged ≥70 years. Aortic FPP and PI measured non-invasively by a brachial cuff-based oscillometric device were associated with coronary atherosclerosis in elderly patients.

BACKGROUND/OBJECTIVES: Brain-derived neurotrophic factor (BDNF) and its receptor (tropomyosin-related kinase B: TrkB, also known as Ntrk2) have a key role in central regulation of the energy balance. BDNF and TrkB are also expressed in the peripheral tissues, including adipose tissue, but their peripheral role has been unclear. Here we report on the functional significance of the adipose tissue BDNF/TrkB axis in metabolic homeostasis. MATERIALS AND METHODS: To examine the role of the BDNF/TrkB axis in the central nervous system and in adipose tissue, we generated adipocyte-specific or neuron-specific BDNF/TrkB conditional knockout (CKO) mice. Then we compared the feeding behavior and metabolic profile between each type of CKO mouse and their littermates. RESULTS: Bdnf expression was significantly increased in the adipose tissue of mice receiving a high-calorie diet, whereas Ntrk2 expression was decreased. The Bdnf/Ntrk2 expression ratio of adipose tissue was higher in female mice than male mice. Fabp4-Cre mice are widely used to establish adipocyte-specific CKO mice. However, we found that Fabp4-Cre-induced deletion of Bdnf or Ntrk2 led to hyperphagia, obesity, and aggressiveness, presumably due to ectopic Fabp4-Cre mediated gene recombination in the brain. Next, we attempted to more specifically delete Bdnf or Ntrk2 in adipocytes using Adipoq-Cre mice. Expression of Ntrk2, but not Bdnf, in the adipose tissue was reduced by Adipoq-Cre mediated gene recombination, indicating that adipocytes only expressed TrkB. No phenotypic changes were detected when Adipoq-Cre TrkB CKO mice were fed a normal diet, whereas female CKO mice receiving a high-calorie diet showed a decrease in food intake and resistance to obesity. CONCLUSIONS: The adipose tissue BDNF/TrkB axis has a substantial influence on the feeding behavior and obesity in female mice.

Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.