Risk Factor For Premature Mortality Research Articles

The visceral adiposity index predicts cardiovascular events both in coronary artery disease patients with and in those without diabetes

Abstract The Visceral Adiposity Index (VAI) is calculated based on waist circumference, BMI, triglyceride and HDL-cholesterol levels and is a validated measure of visceral adiposity. In the general population, the VAI has been shown to be an independent risk factor for premature mortality. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) with or without type 2 diabetes mellitus (T2DM) is not known and is addressed in the present study. We prospectively investigated 927 patients with angiographically diagnosed CAD over a mean follow-up time of 8.2±4.3 years. At baseline, the VAI was significantly higher in patients with T2DM (n=303) than in those who did not have diabetes (6.5±5.2 vs. 4.8±4.9; p<0.001). During follow-up, we recorded 385 cardiovascular events. The VAI significantly predicted the incidence of cardiovascular events both univariately (standardized HR 1.09 [1.02-1.16]; p=0.011) and after adjustment for age, gender, smoking, LDL cholesterol, hypertension and T2DM (standardized adjusted HR 1.11 [1.04- 1.18]; p=0.002); T2DM also significantly predicted cardiovascular events in this fully adjusted model (adjusted HR 1.26 [1.04-1.52]; p=0.018) independently from the VAI. We conclude that the VAI and T2DM are mutually independent predictors of cardiovascular events in patients with CAD.

Exploring Public, Practitioner and Policymaker Perspectives of Unhealthy Lifestyle Factors in the Context of Socioeconomic Deprivation: A Qualitative Study.

Unhealthy lifestyle factors, such as smoking, high alcohol intake, poor diet and physical inactivity, are key risk factors for premature mortality. How unhealthy lifestyle factors are viewed in the wider context of socioeconomic deprivation is rarely considered. Understanding key stakeholder views on lifestyle factors in the context of deprivation is critical to intervention development and reducing harm in more deprived populations. The aim of this study was to explore public, healthcare professional and policymaker views around unhealthy lifestyle factors in the context of deprivation. The aim was broad to facilitate iterative development of ideas, as the views of this wide range of stakeholders are rarely captured. Twenty-five adult members of the public in Scotland took part in four focus groups between August 2022 and June 2023. Eighteen semi-structured interviews were conducted with professionals: 12 primary-care practitioners and 6 public-health practitioners and policymakers. Reflexive thematic analysis was undertaken. Four main themes were developed: (1) Evolving complexity of lifestyle factors - the number of lifestyle factors that adversely impact health has grown, with increasingly complex interactions, (2) Social determinants of lifestyle - numerous links were made between socioeconomic conditions and unhealthy lifestyle factors by all participants, (3) Poverty as a fundamental social determinant - poverty was identified as a core factor for unhealthy lifestyle factors, and (4) Agency versus structure in relation to lifestyle - individual agency to address lifestyle factors was limited by structural constraints. Among professionals, understanding the challenging social determinants of unhealthy lifestyle factors was countered by a desire to support healthy change in those affected by deprivation. Public and professional views around lifestyle highlight an evolving understanding of the new and growing number of lifestyle factors as well as the increasingly complex interplay between lifestyle factors. Views of the social determinants of lifestyle and structural limits to agency strengthen arguments for reduced emphasis on individual-level responsibility for unhealthy lifestyle factors and for deeper integration of social determinants into lifestyle interventions. In addition to addressing poverty and socioeconomic inequalities directly, innovative policy, planning and legislation that incorporate wider approaches could tackle upstream determinants of numerous unhealthy lifestyle factors simultaneously. Members of the public who participated in this study have made contributions by sharing their views and perspectives. The National Health Service Research Scotland Primary Care Patient and Public Involvement (NRS PPI) Group contributed to the development of this work. The NRS PPI Group was consulted as part of the preparatory work for H. M. E. F.'s doctoral thesis funding application. The findings of the qualitative work were presented to them, and they informed the interpretation of those findings and related work presented at conferences and public engagement events.

Association between Mild Overweight and Survival: A Study of an Exceptionally Long-Lived Population in the Sardinian Blue Zone.

Background/Objectives: Overweight and obesity are generally considered risk factors for premature mortality. However, scientific evidence suggests that among older populations, mild conditions of overweight might be associated with reduced comorbidity and longer survival. This study investigates the potential association between anthropometric parameters and survival among a cohort of nonagenarians in Sardinia, Italy. Methods: This study included 200 subjects (50% females) aged 89 and older, enrolled in 2018 in the Sardinian Blue Zone-a population known for longevity-and followed for up to six years. Anthropometric variables such as body height, weight, age, sex, comorbidity, disability, and food group intake were collected using validated questionnaires and analyzed through multivariable analysis. Results: Out of 200 participants at baseline, 28 (14%) were still alive after six years of follow-up (females 10%, males 18%). Mean survival was 3.36 years (range 0.1-6.9 years) for males and 3.03 years (range 0.2-6.6 years) for females. Participants with a Body Mass Index (BMI) in the range of 25.0-27.0 kg/m2 among males and 25.0-27.2 kg/m2 among females had longer survival compared to those who were underweight (p = 0.002) or obese (p < 0.0001). The Cox proportional hazards regression model, adjusted for age, sex, and comorbidity, revealed a statistically significant association between the BMI and survival, demonstrating an inverted-U relationship. This indicates that mild overweight was associated with a survival advantage compared to both normal weight and obesity. Conclusions: Our study indicates that mild, but not severe, overweight in nonagenarians is associated with extended lifespan. Therefore, primary care physicians and geriatricians should exercise caution before recommending calorie-restricted diets for mildly overweight elderly patients.

An Analysis of the Health Effects of Physical Activity due to Active Travel Policies in Rennes, France.

Rennes, a midsize city in France, features many opportunities for active travel. City officials seek to increase walking and cycling by 2030 to improve public health. Physical inactivity, a leading risk factor for premature mortality around the globe, has been shown to be associated with many chronic diseases including heart disease, type 2 diabetes, and cancer. Using the 2018 household travel survey of Rennes residents, we apply the Health-Oriented Transportation statistical model to assess health impacts associated with population-level rates of walking and cycling. We consider two proposed mobility and climate objectives which outline sustainable transportation goals by 2030. These include a shift in transportation mode share to increase walking and cycling trips, as well as a broad reduction in vehicle miles traveled (VMT) across the metropolitan area. Our regression analysis demonstrated that factors of household car access and inner-city residency were predictors of prevalence (observed one-day proportion engaging in walking or cycling), participation (weekly proportion), and intensity (mean individual physical activity achieved through walking/cycling) of active travel. Age and education were additionally associated with prevalence. The 2030 mobility objective (mode share: 9% cycle, 35% walk) was associated with a reduction of 1,051 DALYs (disability-adjusted life-years), translating to $73 million USD ($23-$177) in averted costs. The climate objective (10% reduction in VMT) was associated with a reduction of 369 DALYs when replaced entirely by walking and 714 DALYs with cycling, translating to $26 million ($8-$62) and $50 million ($15-$121) saved, respectively. Rennes residents experience high participation in active travel, particularly those in the inner city. If residents achieve the city's active travel goals for 2030, there is potential for a large reduction in health burden and subsequent costs. Reaching these goals may require significant investment in transportation programming and infrastructure to improve active travel opportunities.

An Analysis of the Health Effects of Physical Activity due to Active Travel Policies in Rennes, France

Background Rennes, a midsize city in France, features many opportunities for active travel. City officials seek to increase walking and cycling by 2030 to improve public health. Physical inactivity, a leading risk factor for premature mortality around the globe, has been shown to be associated with many chronic diseases including heart disease, type 2 diabetes, and cancer. Methods Using the 2018 household travel survey of Rennes residents, we apply the Health-Oriented Transportation statistical model to assess health impacts associated with population-level rates of walking and cycling. We consider two proposed mobility and climate objectives which outline sustainable transportation goals by 2030. These include a shift in transportation mode share to increase walking and cycling trips, as well as a broad reduction in vehicle miles traveled (VMT) across the metropolitan area. Results Our regression analysis demonstrated that factors of household car access and inner-city residency were predictors of prevalence (observed one-day proportion engaging in walking or cycling), participation (weekly proportion), and intensity (mean individual physical activity achieved through walking/cycling) of active travel. Age and education were additionally associated with prevalence. The 2030 mobility objective (mode share: 9% cycle, 35% walk) was associated with a reduction of 1,051 DALYs (disability-adjusted life-years), translating to $73 million USD ($23-$177) in averted costs. The climate objective (10% reduction in VMT) was associated with a reduction of 369 DALYs when replaced entirely by walking and 714 DALYs with cycling, translating to $26 million ($8-$62) and $50 million ($15-$121) saved, respectively. Conclusions Rennes residents experience high participation in active travel, particularly those in the inner city. If residents achieve the city’s active travel goals for 2030, there is potential for a large reduction in health burden and subsequent costs. Reaching these goals may require significant investment in transportation programming and infrastructure to improve active travel opportunities.

A systemic review and meta-analysis on the prevalence and associated factors of hypertension among adult clients in Ethiopia.

Hypertension is a major risk factor for premature mortality and excessive morbidity in the world. It is a growing public health problem in developing countries including Ethiopia. It is a silent killer. Information on the prevalence of hypertension and its associated factors is to be considered vital to focus on early diagnosis and improve prevention and control of cardiovascular diseases. However, on the prevalence and contributing factors of hypertension in Ethiopia, there is a dearth of information. Thus, this review aimed to estimate the pooled prevalence of hypertension and its contributing factors among Ethiopia's adult population. The main objective of this study was to provide pooled evidence on the prevalence of hypertension among the adult population in Ethiopia. This systematic review and meta-analysis were searched through MEDLINE/ Pub Med, Cochrane Library, and Google Scholar by using different search terms on the prevalence of hypertension and Ethiopia. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used for critical appraisal of studies. The analysis was done using STATA 14 software. The Cochran Q test and I2 test statistics were used to test the heterogeneity of studies. Egger's test was used to show the publication bias. The pooled prevalence of HDP and the odds ratio (OR) with 95% confidence interval were presented using forest plots. A total of 22 studies with 14,202 participants were included in this review and the overall estimated prevalence of hypertension among the adult population in Ethiopia was 28.02% (95% CI (23.89%, 32.15%). Age 4.37(2.71, 6.04), sex (AOR=2.54, 95% CI: 1.00-4.09), family history of hypertension (AOR=3.05, 95% CI, 1.89, 4.21), inactive physical exercise (AOR=2.67, 95% CI: 1.38, 3.97), being obese (AOR=3.94, 95CI:2.83, 5.06), khat chewing (AOR=3.73, 95% CI: 2.65, 4.80), salt consumption (AOR=4.20, 95% CI: 1.55, 6.86) were significantly associated factors. Subgroup meta-analysis done by region showed that a higher in Tigray region 52.19(46.54, 57.66), and the lower was observed in Harare region1 2.71 (9.54, 15.87). The prevalence of hypertension among the adult population in Ethiopia is high. Healthcare professionals and other stakeholders should give attention to the early detection of hypertension in Ethiopia to reduce the burden of the disorder.

Disease burden in Norway in 2050: A forecasting analysis based on the Global Burden of Disease (GBD) Study

Abstract Life expectancy in Norway has increased steadily in the past 50 years, in line with decreases in important causes and risk factors for premature mortality. However, due to the aging of the population, it is expected that a higher number will live with chronic diseases in the future. This will have implications for the planning of health services and public health work. The aim of this analysis was to forecast the disease burden in Norway up to 2050. The analyses were based on data on life expectancy and disease burden by 21 disease groups from the Global Burden of Disease Study 2019 (GBD 2019). The population was forecasted to get estimates on future size, age-composition and life expectancy up to 2050. Independent drivers of population health, in terms of sociodemographic factors and a selection of risk factors and preventive measures (e.g. vaccines) were included in the forecasting of general and cause-specific mortality. Non-fatal health loss was forecasted based on incidence/mortality ratios, or previous trends in disease development for causes not associated with mortality. Results are presented as rates, and compared with observed rates from the period 1990 to 2019. Both life expectancy and the proportion of elderly in Norway is forecasted to increase towards 2050. The decreasing trend in mortality and disease burden rates observed from 1990 to 2019 is, however, forecasted to turn, with a forecasted increase starting from 2020 and onward. Mortality due to cancers, neurological diseases and chronic respiratory diseases were forecasted to increase, while cardiovascular diseases were forecasted to contribute with decreased mortality in 2050. The non-fatal disease burden was forecasted to remain relatively stable. Aging of the population is the most important driver of future disease burden. Forecasting of disease burden by cause- and age-groups provides important background knowledge for planning of future health services and targeted health promotion.

Frailty, sex, and poverty are associated with DNA damage and repair in frail, middle-aged urban adults

Frailty is an age-related syndrome characterized by reduced recovery from stressors and increased risks of morbidity and mortality. Although frailty is usually studied in those over 65 years, our previous work showed that frailty is both present and a risk factor for premature mortality in midlife. We identified altered gene expression patterns and biological pathways associated with inflammation in frailty. Evidence suggests DNA oxidation damage related to inflammation accumulates with age, and that DNA repair capacity (DRC) declines with age and age-related conditions. We hypothesized that inter-individual differences in DNA oxidation damage and DRC are associated with frailty status and poverty level. Using the CometChip assay, we assessed baseline single-strand breaks and hydrogen peroxide (H2O2)-induced DNA oxidation damage and DRC in non-frail and frail middle-aged African American and White individuals with household incomes above and below poverty. Analysis of baseline single-strand breaks showed no associations with frailty, poverty, race, or sex. However, we identified an interaction between frailty and poverty in H2O2-induced DNA oxidation damage. We also identified interactions between sex and frailty as well as sex and poverty status with DRC. The social determinant of health, poverty, associates with DRC in men. Baseline DNA damage, H2O2-induced DNA damage as well as DRC were associated with serum cytokine levels. IL-10 levels were inversely associated with baseline DNA damage as well as H2O2-induced DNA damage, DRC was altered by IL-4 levels and sex, and by TNF-α levels in the context of sex and poverty status. This is the first evidence that DRC may be influenced by poverty status at midlife. Our data show that social determinants of health should be considered in examining biological pathways through which disparate age-related health outcomes become manifest.

471-P: The Visceral Adiposity Index Predicts MACE Both in Cardiovascular Disease Patients with and in Those without Diabetes

The Visceral Adiposity Index (VAI) is calculated based on waist circumference, BMI, triglyzeride and HDL-cholesterol levels and is a validated measure of visceral adiposity. In the general population, the VAI has been shown to be an independent risk factor for premature mortality. Its power to predict MACE in patients with established cardiovascular disease (CVD) with or without type 2 diabetes mellitus (T2DM) is not known and is addressed in the present study. We prospectively recorded MACE in 601 of 1499 patients with either angiographically diagnosed CAD (n=1261) or sonographically verified PAD (n=238) over a mean follow-up time of 9.6±5.1 years. At baseline, the VAI was significantly higher in patients with T2DM (n=489) than in those who did not have diabetes (6.7±6.0 vs. 4.7±4.5; p&amp;lt;0.001). Prospectively, the VAI significantly predicted the incidence of MACE both univariately (standardized HR 1.01 [1.00-1.03]; p=0.037) and after adjustment for age, gender, smoking, LDL cholesterol, hypertension and T2DM (standardized adjusted HR 1.01 [1.00-1.03]; p=0.011); also T2DM significantly predicted MACE in this fully adjusted model (adjusted HR 1.55 [1.31-1.84]; p&amp;lt;0.001). We conclude that the VAI and T2DM are mutually independent predictors of MACE in patients with CVD. Disclosure M.Maechler: None. C.H.Saely: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. T.Plattner: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None.

The obesity-induced expression of T-bet in B cells promotes metabolic dysfunction and alters antibody responses

Abstract Obesity is a leading risk factor for premature mortality and poor medical outcomes due to its increasing global prevalence and its profound impact on the human body. Obesity also has a significant immune component as the establishment of a chronic inflammation in obese individuals is a significant driver of metabolic dysfunction. Additionally, obesity alters anti-tumor immunity, and it impairs protective antibody responses during infection or vaccination. The outcome can be extremely catastrophic, as highlighted in the COVID-19 pandemic with obese patients being particular susceptible to the disease. This relationship warrants more investigation into the obesity-associated changes occurring in B cells, central players in both the obesity-associated chronic inflammation and in the production of antibodies. Our lab has identified a subset of B cells which is expanded in both humans and mice during obesity and is characterized by the expression of the transcription factor T-bet. In vivostudies using obese mice fed a high fat diet revealed that these Tbet+ B cells promote inflammation and metabolic dysfunction through the production of proinflammatory antibodies. Additionally, blocking the expression of T-bet in the B cells of obese mice resulted in significant changes in antibody responses, with a greater expansion of germinal center B cells and an increased ability to generate antigen-specific B cells following immunization. Based on our findings, T-bet+ B cells represent an interesting link between obesity, inflammation, and antibody responses. Identifying the mechanisms regulating their function will provide new potential ways to reduce inflammation and enhance protection against infectious diseases in obese patients.

Harmful Alcohol Use and Associated Socio-Structural Factors among Female Sex Workers Initiating HIV Pre-Exposure Prophylaxis in Dar es Salaam, Tanzania.

Harmful alcohol use is an important risk factor for premature mortality and morbidity and associated with increased HIV risk and lower uptake of and adherence to HIV interventions. This study aimed to assess the extent of harmful alcohol use and associated socio-structural vulnerability factors among female sex workers in Dar es Salaam, Tanzania, a key population in the HIV epidemic. Data from a study of female sex workers initiating pre-exposure prophylaxis (PrEP) recruited through respondent driven sampling were used. We assessed harmful alcohol use with the Alcohol Use Disorders Identification Test (AUDIT) defined as having an AUDIT score ≥ 16. Associations between harmful alcohol use and socio-structural factors were assessed using logistic regression with marginal standardization. Of the 470 women recruited, more than one third (37.3%) had a drinking pattern suggestive of harmful alcohol use. Such use was independently associated with sex work-related mobility (aPR: 1.36, 95% CI: 1.11-1.61), arrest/incarceration (aPR: 1.55, 95% CI: 1.27-1.84) and gender-based violence (aPR: 1.31, 95% CI: 1.06-1.56). The high prevalence of harmful alcohol use and the interconnectedness with socio-structural factors indicate a need for a holistic programmatic approach to health for female sex workers. Programming should not solely direct attention to individual behavior but also include strategies aiming to address socio-structural vulnerabilities.

THE RISE OF LONELINESS: TRENDS AMONG A LARGE MEDICARE ADVANTAGE COHORT OVER THE COVID-19 PANDEMIC

Abstract Loneliness is an established risk factor for premature mortality, especially among older adults. National trends are indicating an increase in loneliness after the COVID-19 pandemic. We sought to explore annual trends in loneliness and quality of life among a large dataset of Medicare Advantage (MA) members. Papa Inc. is a national service that pairs older adults with “Papa Pals” who provide companionship and assistance with everyday tasks. Participants have free access if their health plan offers it. Analysis included members from MA plans that were active with Papa January 2020 through March 2022. Members (n=11,037) were assessed at enrollment screening (UCLA Three-Item Loneliness Scale, CDC’s Healthy Days Measure). Analysis used Chi-square tests, significance set at p &amp;lt; 0.05. Among the sample, 81% were aged 65+, 14% were from a majority non-white community. Analysis revealed the following trends in annual prevalence rates (2020; 2021; 2022): lonely (43.2%; 39.3%; 40.9%), severely lonely (9.2%; 12.1%; 15.1%), 14+ physically unhealthy days (24.3%; 19.9%; 39.3%). In regression analysis, loneliness score increased by 0.05 (95CI: 0.02 - 0.07) per quarter over the 27 months. Our data mimics other sources highlighting a slow and steady increase in loneliness suggesting older adults’ hesitancy to engage in “normal activities.” Changes in unhealthy days follow COVID-19 trends with a significant increase during the height of the Omicron variant. The prolonged effects of isolation and loneliness are profound, thus greater emphasis should be placed on population level interventions, especially those connected to the healthcare system, to help address loneliness.

Expanding our understanding of the global impact of physical inactivity

Physical inactivity (ie, not meeting WHO recommendations for physical activity) is a highly prevalent risk factor for premature mortality and several non-communicable diseases (NCDs).1 An important metric of public health burden is health-care cost; physical inactivity cost health-care systems INT$53·8 billion worldwide in 2013.2 The scientific evidence base on the health effects and global burden of physical inactivity has expanded greatly.3–5 Despite these scientific advances, the global prevalence of physical inactivity among adults was 27·5% in 2016, an estimate that remained stable since 2001.

The Iranian blood pressure measurement campaign, 2019: study protocol and preliminary results.

Hypertension is one of the most important risk factors for premature mortality and morbidity in Iran. The objective of the Iranian blood pressure (BP) measurement campaign was to identify individuals with raised blood pressure and providing appropriate care and increase the awareness among the public and policymakers of the importance of tackling hypertension. The campaign was conducted in two phases. The first (communication) phase started on May 17th (International Hypertension Day). The second phase started on June 8th, 2019, and lasted up to July 7th during which, blood pressures were measured. The target population was Iranians aged ≥ 30 years. Participants voluntarily referred to health houses in rural and health posts and comprehensive health centers in urban areas in the setting of the Primary Health Care network. Additionally, over 13,700 temporary stations were set up in highly visited places in urban areas. Volunteer healthcare staff interviewed the participants, measured their BP, and provided them with lifestyle advice and knowledge of the risks and consequences of high blood pressure. They referred participants to physicians in case their BP was high. Participants immediately received a text message containing the relevant advice based on their measured BP and their past history. Blood pressure was measured for a total of 26,678,394 participants in the campaign. A total of 13,722,148 participants (51.4%) were female. The mean age was 46 ± 14.1 years. Among total participants, 15,012,693 adults (56.3%) with no past history of hypertension had normal BP, 7,959,288 participants had BP in the prehypertension range (29.8%), and finally, 3,706,413 participants (13.9%) had either past medical history of hypertension, used medications, or had high BP measured in the campaign. The campaign was feasible with the objective to increase the awareness among the public and policymakers of the importance of tackling hypertension in Iran.

Long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in a large pooled European cohort: ELAPSE study

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10−5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide.

Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area

BackgroundPeople with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.AimsIn this study, we investigated the associations of...

S10-4 The Global Observatory for Physical Activity-GoPA! Policy Inventory: preliminary findings and lessons learned

BackgroundInsufficient physical activity (PA) is considered to be one of the main risk factors for premature mortality. Its high prevalence and associated costs for the health care system present a strong incentive for national governments to develop PA policies. There is a lack of recent and mutually comparable data on national PA policies, particularly for low- to middle-income countries. In 2019, the Global Observatory for Physical Activity (GoPA!) has therefore started collecting data on national PA policies globally using the GoPA! Policy Inventory, version 3.0. Our aim is to present the preliminary findings of this data collection and lessons learned during the process.MethodsThe GoPA! Policy Inventory, version 3.0 was distributed to 149 GoPA! Country Contacts, with an option to provide their responses in an online survey or in an interactive Word document. The GoPA! Policy Inventory, version 3.0 includes 20 questions about availability, content, implementation, comprehensiveness, and effectiveness of national PA policies.ResultsData were collected for 24 high-income, 13 upper-middle-income, nine lower-middle-income, and three low-income countries (overall n = 49) from all six WHO regions. A large majority of countries (76%) reported having a national PA policy or plan. Fifty-seven per cent of countries reported having PA recommendations. However, less than a half of the countries (45%) had PA recommendations for each of the following key target groups: children and young people, adults, and older adults. National health surveillance/monitoring system, which includes measures of PA, was available in 78% of countries. Most Country Contacts indicated that the ministries of health, sport, and education had active roles in PA promotion. Quantifiable national targets for PA were established in 43% of countries. The median score for the implementation of policies was 6, for comprehensiveness five, and effectiveness four and a half (out of a maximum score of 10).ConclusionFurther efforts are needed in the development and implementation of comprehensive national PA policies. More countries should establish quantifiable national targets for PA and track progress toward meeting them. Monitoring the effectiveness and implementation of PA policies remains challenging, as countries do not have established systems for their assessment.

The Differential Effects of Adiposity and Fitness on Functional Connectivity in Preadolescent Children.

Childhood obesity is a global health concern, with >340 million youth considered overweight or obese. In addition to contributing greatly to health care costs, excess adiposity associated with obesity is considered a major risk factor for premature mortality from cardiovascular and metabolic diseases and is also negatively associated with cognitive and brain health. A complementary line of research highlights the importance of cardiorespiratory fitness, a by-product of engaging in physical activity, on an abundance of health factors, including cognitive and brain health. This study investigated the relationship among excess adiposity (visceral adipose tissue [VAT], subcutaneous abdominal adipose tissue), total abdominal adipose tissue, whole-body percent fat [WB%FAT], body mass index (BMI), and fat-free cardiorespiratory fitness (FF-V̇O 2max ) on resting-state functional connectivity (RSFC) in 121 ( f = 68) children (7-11 yr) using a data-driven whole-brain multivoxel pattern analysis. Multivoxel pattern analysis revealed brain regions that were significantly associated with VAT, BMI, WB%FAT, and FF-V̇O 2 measures. Yeo's (2011) RSFC-based seven-network cerebral cortical parcellation was used for labeling the results . Post hoc seed-to-voxel analyses found robust negative correlations of VAT and BMI with areas involved in the visual, somatosensory, dorsal attention, ventral attention, limbic, frontoparietal, and default mode networks. Further, positive correlations of FF-V̇O 2 were observed with areas involved in the ventral attention and frontoparietal networks. These novel findings indicate that negative health factors in childhood may be selectively and negatively associated with the 7 Yeo-defined functional networks, yet positive health factors (FF-V̇O 2 ) may be positively associated with these networks. These novel results extend the current literature to suggest that BMI and adiposity are negatively associated with, and cardiorespiratory fitness (corrected for fat-free mass) is positively associated with, RSFC networks in children.

Dysfunction in B cell tolerance and activation in obesity.

Abstract Obesity is a complex condition that affects a large part of the global population, making it a major risk factor for premature mortality and medical complications. Obesity profoundly engages the immune system, impacting cancer immunity, infections, and autoimmunity. Additionally, obesity is associated with a low-grade chronic inflammation which exacerbates metabolic dysfunction. B cells play a significant role in obesity-associated inflammation and metabolic dysfunction, but their effect is subset-dependent and can be either protective or pathogenic. Therefore, understanding how different B cell populations contribute to these phenotypes represent a crucial goal. Our lab has identified a subset of B lymphocytes which is expanded in the adipose tissue of humans and mice during obesity. These B cells co-express the transcription factor T-bet and the integrin CD11c, and they produce IgG2c antibodies. In vivo studies with mice fed a high fat diet revealed that these Tbet+ B cells promote inflammation through the production of proinflammatory antibodies. Additionally, these B cells express high levels of the scavenger receptor CD36, a lipid-transport molecule associated with inflammation and atherosclerosis. As a potential consequence of the CD36 expression, the Tbet+ B cells maintain a higher intracellular lipid content and are capable of increased uptake of oxidized LDL compared to conventional B cells, suggesting a unique lipid metabolism. Because of their unique nature, T-bet+ B cells represent a potential link between obesity, inflammation, and autoimmunity. Identifying the mechanisms regulating their function will provide new potential targets to reduce inflammation and immunological dysfunction in obese patients. Supported by R01 AI132798

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.