Obesity and risk of diseases associated with hallmarks of cellular ageing: a multicohort study.

BACKGROUND: Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated with an increased risk of developing such hallmark-related diseases. METHODS: In this multicohort study, we included people aged 38-72 years with data on weight, height, and waist circumference measured during a clinical examination at baseline between March 13, 2006, and Oct 1, 2010, from the UK Biobank with follow-up until Nov 12, 2021. To test reproducibility of the findings (replication analysis), we used data from people aged 40 years or older included in the Finnish Public Sector study and the Finnish Health and Social Support study who responded to the study surveys, had data on BMI, and were successfully linked to electronic health records from national registers up to Dec 31, 2016. Obesity and clinical characteristics were assessed at baseline. Via linkage to national health records, participants were followed up for 83 diseases related to nine ageing hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication). Outcomes were the first instance of hallmark-related disease, in addition to co-occurrence of three or more hallmark-related diseases and mortality. FINDINGS: 496 530 adults (mean age 57·0 years [SD 8·1]) from the UK Biobank were included in the primary analysis, and 83 249 (mean age 48·2 years [6·4]) adults from the Finnish cohorts were included in the replication analysis. Median follow-up was 12·7 years (IQR 12·0-13·4) in the UK Biobank and 14·0 years (8·0-15·0) in the Finnish cohorts. After adjusting for demographic characteristics, lifestyle factors, and depression, UK Biobank participants with obesity (BMI ≥30·0 kg/m2) had a 1·40 (95% CI 1·38-1·41) times higher hazard ratio for the first hallmark-related disease than those with a healthy weight (BMI 18·5-24·9 kg/m2). The corresponding hazard ratios for three co-occurring diseases were 2·92 (95% CI 2·64-3·22) for deregulated nutrient sensing, 2·73 (2·46-3·02) for telomere attrition, 2·33 (2·10-2·60) for epigenetic alterations, 2·30 (2·14-2·48) for mitochondrial dysfunction, 2·23 (2·04-2·45) for stem cell exhaustion, 2·02 (1·89-2·16) for altered intercellular communication, 2·01 (1·89-2·15) for cellular senescence, 1·83 (1·67-2·00) for loss of proteostasis, and 1·39 (1·27-1·52) for genomic instability. These findings were replicated in the Finnish cohorts. In both studies, the associations between other risk factors (low education, unhealthy dietary factors [available only in the UK Biobank], smoking, high alcohol consumption, physical inactivity, and depression) and hallmark-related diseases were weaker than those with obesity. 45-60% of the excess mortality in people with obesity was attributable to hallmark-related diseases. INTERPRETATION: Obesity might have an important role in the development of diseases associated with cellular ageing. Tackling ageing mechanisms could potentially help to reduce the disease and mortality burden resulting from the obesity epidemic. FUNDING: Wellcome Trust, UK Medical Research Council, US National Institute on Aging, Academy of Finland, and Finnish Foundation for Cardiovascular Research. TRANSLATIONS: For the German and Finnish translations of the abstract see Supplementary Materials section.

Association of school neighbourhood socioeconomic disadvantage and teaching staff's risk of violence at work.

AIM: The aim of this study was to determine the association between neighbourhood socioeconomic disadvantage and teaching staff's risk of workplace violence and whether workplace psychosocial resources can act as effect modifiers. METHODS: Primary school teaching staff in the six largest cities in Finland responded to a survey in 2018 and were linked to information on school neighbourhood disadvantage obtained from the national grid database (n = 3984). RESULTS: After adjustment for confounders, staff working in schools located in the most disadvantaged neighbourhoods had a 1.2-fold (95% confidence interval 1.07-1.35) risk of encountering violence or threat of violence compared with staff working in the most advantaged neighbourhoods. The association was less marked in schools with strong support from colleagues (risk ratio 1.14, 95% confidence interval (95% CI) 0.98-1.32 for high support versus 1.23, 95% CI 1.07-1.43 for low/intermediate support), a strong culture of collaboration (1.08, 95% CI 0.93-1.26 versus 1.31, 95% CI 1.12-1.53), high leadership quality (1.12, 95% CI 0.96-1.31 versus 1.29, 95% CI 1.08-1.54), and high organizational justice (1.09, 95% CI 0.91-1.32 versus 1.29, 95% CI 1.09-1.52). CONCLUSIONS: The association between school neighbourhood and teaching staff's risk of violence was weaker in schools with high workplace psychosocial resources, suggesting that targeting these factors might help in minimizing violence at schools, but future intervention studies are needed to confirm or refute this hypothesis.

Exposure to workplace sexual harassment and risk of cardiometabolic disease: a prospective cohort study of 88 904 Swedish men and women.

AIMS: Exposure to work-related sexual harassment may increase the risk for certain adverse behavioural and emotional outcomes but less is known about its association with somatic diseases such as cardiovascular disease (CVD) and type 2 diabetes. This study investigated the prospective association of work-related sexual harassment and risk of cardiometabolic diseases. METHODS AND RESULTS: This cohort study included 88 904 Swedish men and women in paid work who responded to questions on workplace sexual harassment in the Swedish Work Environment Survey (1995-2015) and were free from cardiometabolic diseases at baseline. Cardiometabolic diseases (CVD and type 2 diabetes) were identified from the National Patient Register and Causes of Death Register through linkage. Cox proportional hazard regression was used, adjusting for socio-demographic, work-related psychosocial, and physical exposure at baseline. Overall, 4.8% of the participants (n = 4300) reported exposure to workplace sexual harassment during the previous 12 months. After adjustment for sex, birth country, family situation, education, income, and work-related factors, workplace sexual harassment was associated with increased incidence of CVD [hazard ratio (HR) 1.25, 95% confidence interval 1.03-1.51] and type 2 diabetes (1.45, 1.21-1.73). The HR for CVD (1.57, 1.15-2.15) and type 2 diabetes (1.85, 1.39-2.46) was increased for sexual harassment from superior or fellow workers, and sexual harassment from others was associated with type 2 diabetes (1.39, 1.13-1.70). The HR for both CVD (1.31, 0.95-1.81) and type 2 diabetes (1.72, 1.30-2.28) was increased for frequent exposure. CONCLUSION: The results of this study support the hypothesis that workplace sexual harassment is prospectively associated with cardiometabolic diseases. Future research is warranted to understand causality and mechanisms behind these associations.

We investigated if workers in Sweden who had experienced sexual harassment at work had a higher risk of developing cardiovascular disease and diabetes than workers who had not experienced sexual harassment at work. The experience of workplace sexual harassment was associated with an increased risk of both cardiovascular disease and diabetes. The risk was highest among those workers who had frequently experienced sexual harassment. Our results suggest that preventive measures directed towards elimination of sexual harassment may contribute to a reduction in cardiovascular disease and diabetes in the population.

Physical activity and risk of workplace and commuting injuries: a cohort study.

OBJECTIVE: Leisure-time physical activity (PA) has been hypothesized to reduce the likelihood of occupational injuries, but it is unclear whether this association varies between workplace and commuting injuries. The aim of this study was to examine the association between PA and risk of workplace and commuting injuries. METHODS: Data were derived from the Finnish Public Sector study including 82 716 person-observations (48 116 participants). PA was requested repeatedly in four questionnaire surveys between 2000-2012. The average level of PA from two subsequent questionnaires was used to assess long-term PA. To obtain a 1-year incidence of injuries, participants were linked to occupational injury records from the national register. Logistic regression analysis with generalized estimating equations was used to examine the association between PA and injury risk. The analysis was adjusted for age, sex, education, work schedule, job demand, sleep difficulties, cardiovascular diseases, diabetes, and depression for workplace and commuting injuries, and workplace injuries were additionally adjusted for physical heaviness of an occupation and injury risk by occupation. RESULTS: Higher level of PA was associated with a lower risk of workplace injuries compared to inactive participants [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.98]. This association was most marked in the ≥50-year-old age group (OR 0.78, 95% CI 0.64-0.99). No association between the PA and the risk for commuting injuries was observed. CONCLUSION: Higher PA is associated with lower risk of workplace injuries particularly among older employees.

Does the effect of adolescent health behaviours on adult cardiometabolic health differ by socioeconomic background? Protocol for a population-based cohort study.

INTRODUCTION: Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic strata. Adopting a life-course perspective and a causal inference framework, we aim to assess whether the effects of adolescent health behaviours on adult cardiometabolic health differ by levels of neighbourhood deprivation, parental education and occupational class. Gaining a better understanding of these social disparities in susceptibility to health behaviours can inform policy initiatives that aim to improve population health and reduce socioeconomic inequalities in cardiometabolic health. METHODS AND ANALYSIS: We will conduct a secondary analysis of the Young Finns Study, which is a longitudinal population-based cohort study. We will use measures of health behaviours-smoking, alcohol use, fruit and vegetable consumption, and physical activity-as exposure and parental education, occupational class and neighbourhood deprivation as effect modifiers during adolescence (ages 12-18 years). Eight biomarkers of cardiometabolic health (outcomes)-waist circumference, body mass index, blood pressure, low-density lipoprotein cholesterol, apolipoprotein B, plasma glucose and insulin resistance-will be measured when participants were aged 33-40. A descriptive analysis will investigate the clustering of health behaviours. Informed by this, we will conduct a causal analysis to estimate effects of single or clustered adolescent health behaviours on cardiometabolic health conditional on socioeconomic background. This analysis will be based on a causal model implemented via a directed acyclic graph and inverse probability-weighted marginal structural models to estimate effect modification. ETHICS AND DISSEMINATION: The Young Finns study was conducted according to the guidelines of the Declaration of Helsinki, and the protocol was approved by ethics committees of University of Helsinki, Kuopio, Oulu, Tampere and Turku. We will disseminate findings at international conferences and a manuscript in an open-access peer-reviewed journal.

Association between changes in cardiovascular health and the risk of multimorbidity: community-based cohort studies in the UK and Finland.

Background: Better cardiovascular health is associated with lower risk of various chronic diseases, but its association with multimorbidity is poorly understood. We aimed to examine whether change in cardiovascular health is associated with multimorbidity risk. Methods: The primary analysis was conducted in the Whitehall II multiwave prospective cohort study (UK) and the validation analysis in the Finnish Public Sector cohort study (Finland). Change in cardiovascular health was assessed using the American Heart Association Life's Simple 7 (LS7) and Life's Essential 8 (LE8) at baseline and re-assessments, using objective measures in Whitehall II and self-reports and pharmacy claims in the Finnish Public Sector cohort study, respectively. Multimorbidity was defined as the presence of two or more of 12 chronic diseases during follow-up. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox's proportional hazard models with age as time scale, adjusting for sex, education, occupation, marital status, and ethnicity. Findings: In the primary analysis among 9715 participants, mean age was 44.8 (standard deviation 6.0) years and 67.6% participants were men at baseline. During the median follow-up of 31.4 (interquartile range 26.8-32.3) years, 2751 participants developed multimorbidity. The hazard of multimorbidity decreased by 8% (HR 0.92, 95% CI 0.88-0.96) per ideal LS7 metric increment over 5 years and by 14% (HR 0.86, 95% CI 0.80-0.93) per ten points increase in LE8 score over 10 years. These findings were replicated in the validation analysis among 75,377 participants in terms of 4-year change in cardiovascular health. Interpretation: Improvement in cardiovascular health was associated with lower multimorbidity risk in two community-based cohort studies. Interventions improving cardiovascular health of the community may contribute to multimorbidity prevention. Funding: None.

NMR metabolomic modeling of age and lifespan: A multicohort analysis.

Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear and penalized regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all-cause mortality. Seven-fold cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.

Cohort study on incidence of new-onset type 2 diabetes in patients after bariatric surgery and matched controls.

BACKGROUND: Metabolic bariatric surgery the reduces risk of new-onset type 2 diabetes in individuals with obesity, but it is unclear whether the benefit varies by sex, age, or socioeconomic status. The aim was to assess the risk of new-onset type 2 diabetes after metabolic bariatric surgery in these subgroups. METHODS: The Finnish Public Sector study, a follow-up study with matched controls nested in a large employee cohort, included patients without type 2 diabetes and with a diagnosis of obesity or self-reported BMI of at least 35 kg/m2. For each patient who had laparoscopic metabolic bariatric surgery (2008-2016), two propensity-score matched controls were selected. New-onset type 2 diabetes was ascertained from linked records from national health registries. RESULTS: The study included a total of 917 patients and 1811 matched controls with obesity. New-onset type 2 diabetes was diagnosed in 15 of the patients who had metabolic bariatric surgery (4.1 per 1000 person-years) and 164 controls (20.2 per 1000 person-years). The corresponding rate ratio (RR) was 0.20 (95% c.i. 0.12 to 0.35) and the rate difference (RD) was -16.1 (-19.8 to -12.3) per 1000 person-years. The risk reduction was more marked in individuals of low socioeconomic status (RR 0.10 (0.04 to 0.26) and RD -20.6 (-25.6 to -15.5) per 1000 person-years) than in those with higher socioeconomic status (RR 0.35 (0.18 to 0.66) and RD -11.5 (-16.9 to -6.0) per 1000 person-years) (Pinteraction = 0.017). No differences were observed between sexes or age groups. CONCLUSION: Metabolic bariatric surgery was associated with a reduced risk of new-onset type 2 diabetes in men and women and in all age groups. The greatest benefit was observed in individuals of low socioeconomic status.

Metabolic bariatric surgery reduces the risk of new-onset type 2 diabetes in individuals with obesity or severe obesity. The risk of new-onset type 2 diabetes after metabolic bariatric surgery varies between socioeconomic status subgroups. In this prospective study, new-onset type 2 diabetes occurred in 1.6% of 917 patients who underwent metabolic bariatric surgery and 9.1% of 1811 propensity score-matched controls. Risk reduction was more marked in individuals of low socioeconomic status. There were no differences between sex or age groups. The reduced risk of new-onset type 2 diabetes after metabolic bariatric surgery emphasizes the need to increase access to treatment in patients with severe obesity. As the preventive effect was most pronounced in individuals of low socioeconomic status associated with both greater burden of disease and worse access to healthcare, the findings need to be taken into account in health policies to reduce health inequalities.

Sleep duration in midlife and old age and risk of mortality over a 48-year follow-up: The Helsinki businessmen study (HBS) cohort.

OBJECTIVES: Both short and long sleep duration have been associated with increased mortality, but there are few truly long-term studies. STUDY DESIGN: This is a cohort study of 2504 men born between 1919 and 1934. In 1974-1975 (mean age 48), participants underwent baseline clinical examinations and sleep duration assessments. A follow-up examination took place 35 years later, in 2010 (mean age 82). MAIN OUTCOME MEASURE: All-cause mortality data from baseline and from old age were collected through to December 31, 2022. RESULTS: At baseline, short sleep duration (≤6 h per night), normal sleep duration (>6 and ≤ 8 h), and long sleep duration (>8 h) was reported by 266, 2019 and 219 men, respectively. Men with short sleep duration had higher levels of smoking, alcohol consumption, body mass index, and poorer self-rated health than those with normal sleep duration. During the 48-year follow-up, 2287 men died. The unadjusted hazard ratio for mortality was 1.20 (95 % confidence interval [CI] 1.05-1.37) for short compared with normal sleep duration, but this association vanished after adjustments (1.01, 95 % CI 0.87-1.17). In old age, the corresponding hazard ratios were 1.41 (1.16-1.72) and 1.19 (0.94-1.51) for short sleep duration and 1.33 (1.09-1.63) and 1.31 (1.02-1.67) for long sleep duration. CONCLUSIONS: In a comprehensive lifespan follow-up, the modestly increased mortality among men with short sleep duration in midlife was attributed to unhealthy lifestyle factors. In old age both long and short sleep duration seemed to be associated with modestly increased mortality. CLINICALTRIALS: gov identifier for the HBS: NCT02526082.

Impact of physical and sexual abuse on risk of hospitalisations for physical and mental illnesses: insights from two large prospective cohort studies.

Background: Physical abuse can lead to severe health consequences that extend beyond immediate harm. We explored the associations of physical abuse experienced during childhood and adulthood with a wide range of adult health conditions requiring hospital treatment. Methods: We utilised data from a sub-cohort of 157,366 UK Biobank participants (46.4% of the baseline population; age range 45-81; 89,101 women) and repeated analyses in an independent population of 85,929 adults from the Finnish Public Sector (FPS) study (age range 17-78; 68,544 women). Participants in both cohorts reported instances of physical and sexual abuse at study baseline. Follow-up included 77 common health conditions ascertained from linkage data to national hospital and mortality registries. Findings: Mean follow-up duration was 4.6 years (SD 0.14) in UK Biobank and 10.6 years (4.3) in FPS. Physical and sexual abuse was associated with 22 mental and physical health conditions. After multivariable adjustments, participants who experienced abuse during both early and later stages of life had a 2.12- (95% confidence interval 1.39-3.23) to 3.37-fold (1.52-7.45) increased risk of mental and behavioural disorders, a 1.46 (1.20-1.79) to 1.83 (1.05-3.20) times increased risk of metabolic, haematologic, and respiratory diseases, and a 1.24 (1.07-1.45) times higher risk of inflammatory diseases compared with non-exposed participants. The absolute risk difference between these groups was greatest for metabolic and haematologic conditions (rate 381 and risk difference 160 per 100,000 person-years). Frailty, comorbidities, and competing risk of death did not modify these associations, but the possibility of bias or residual confounding cannot be excluded. Interpretation: Repeated exposure to physical and sexual abuse amplifies the risk of hospitalisations from mental disorders and physical diseases spanning diverse organ systems. Addressing this issue may necessitate multifaceted strategies, including shifts in societal norms, legal measures, and increased healthcare provision for affected individuals and their families. Funding: Wellcome Trust, UK Medical Research Council, U.S. National Institute on Aging, Academy of Finland.

Role of cardiovascular health factors in mediating social inequalities in the incidence of dementia in the UK: two prospective, population-based cohort studies.

Background: The contribution of modifiable risk factors to social inequalities in dementia, observed in longitudinal studies, remains unclear. We aimed to quantify the role of cardiovascular health factors, assessed using Life's Essential 8 (LE8) score, in mediating social inequalities in incidence of dementia and, for comparison, in incidence of stroke, coronary heart disease, and mortality. Methods: In this prospective, population-based cohort study, we collected data from the UK Whitehall II Study and UK Biobank databases. Participants were included if data were available on SEP, outcomes and LE8 (smoking, physical activity, diet, body mass index, blood pressure, fasting blood glucose, lipid levels, sleep duration). The primary outcome was incident dementia and secondary outcomes were stroke, coronary heart disease, and mortality. Outcomes were derived from electronic healthcare records. Socioeconomic position (SEP) was measured by occupation in Whitehall II and education in UK Biobank. Counterfactual mediation analysis was used to quantify the extent to which LE8 score explained the associations of SEP with all outcomes. Analyses involved Cox regression, accelerated failure time models, and linear regression; and were adjusted for age, sex, and ethnicity. Findings: Between 10.09.1985 and 29.03.1988, a total of 9688 participants (mean age ± SD 44.9 ± 6.0; 67% men) from the Whitehall II study, and between 19.12.2006 and 01.10.2010, 278,215 participants (mean age ± SD 56.0 ± 8.1; 47% men) from the UK Biobank were included. There were 606 and 4649 incident dementia cases over a median (interquartile range) follow-up of 31.7 (31.1-32.7) and 13.5 (12.7-14.1) years respectively in Whitehall II and UK Biobank. In Whitehall II, the hazard ratio was 1.85 [95% CI 1.42, 2.32] for the total effect of SEP on dementia and 1.20 [1.12, 1.28] for the indirect effect via the LE8, the proportion mediated being 36%. In UK Biobank, the total effect of SEP on dementia was 1.65 [1.54, 1.78]; the indirect effect was 1.11 [1.09, 1.12], and the proportion mediated was 24%. The proportions mediated for stroke, coronary heart disease, and mortality were higher, ranging between 34% and 63% in Whitehall II and between 36% and 50% in UK Biobank. Interpretation: In two well-characterised cohort studies, up to one third of the social inequalities in incidence of dementia was attributable to cardiovascular health factors. Promotion of cardiovascular health in midlife may contribute to reducing social inequalities in risk of dementia, in addition to cardiovascular diseases and all-cause mortality. This study used adult measures of SEP, further research is warranted using lifecourse measures of SEP. Funding: NIH (RF1AG062553).

Life course epidemiology and public health.

Life course epidemiology aims to study the effect of exposures on health outcomes across the life course from a social, behavioural, and biological perspective. In this Review, we describe how life course epidemiology changes the way the causes of chronic diseases are understood, with the example of hypertension, breast cancer, and dementia, and how it guides prevention strategies. Life course epidemiology uses complex methods for the analysis of longitudinal, ideally population-based, observational data and takes advantage of new approaches for causal inference. It informs primordial prevention, the prevention of exposure to risk factors, from an eco-social and life course perspective in which health and disease are conceived as the results of complex interactions between biological endowment, health behaviours, social networks, family influences, and socioeconomic conditions across the life course. More broadly, life course epidemiology guides population-based and high-risk prevention strategies for chronic diseases from the prenatal period to old age, contributing to evidence-based and data-informed public health actions. In this Review, we assess the contribution of life course epidemiology to public health and reflect on current and future challenges for this field and its integration into policy making.

Sex-related differential item functioning of the Jenkins Sleep Scale: a cross-sectional study among 77 967 employees in the Finnish public sector.

OBJECTIVES: To investigate if the Jenkins Sleep Scale (JSS) demonstrates sex-related differential item functioning (DIF). DESIGN: Cross-sectional study. SETTING: Survey data from the Finnish Public Sector study (2015-2017). PARTICIPANTS: 77 967 employees in the Finnish public sector, with a mean age of 51.9 (SD 13.1) years and 82% women. OUTCOME MEASURES: Item response theory estimates: difficulty and discrimination parameters of the JSS and differences in these parameters between men and women. RESULTS: The mean JSS total score was 6.4 (4.8) points. For all four items of the JSS, the difficulty parameter demonstrated a slight shift towards underestimation of the severity of sleep difficulties. The discrimination ability of all four items was moderate to high. For the JSS composite score, overall discrimination ability was moderate (0.98, 95% CI 0.97 to 0.99). Mild uniform DIF (p<0.001) was seen: two items showed better discrimination ability among men and two others among women. CONCLUSIONS: The JSS showed overall good psychometric properties among this healthy population of employees in the Finnish public sector. The JSS was able to discriminate people with different severities of sleep disturbances. However, when using the JSS, the respondents might slightly underestimate the severity of these disturbances. While the JSS may produce slightly different results when answered by men and women, these sex-related differences are probably negligible when applied to clinical situations.

Cardiovascular Disease Events in Adults with a History of State Care in Childhood: Pooling of Unpublished Results from 9 Cohort Studies.

Background: Individuals who were separated from their biological family and placed into the care of the state during childhood (out-of-home care) are more prone to developing selected physical and mental health problems in adulthood, however, their risk of cardiovascular disease (CVD) is uncertain. Accordingly, we pooled published and unpublished results from cohort studies of childhood care and adult CVD. Methods: We used two approaches to identifying relevant data on childhood care and adult CVD (PROSPERO registration CRD42021254665). First, to locate published studies, we searched PubMed (Medline) until November 2023. Second, with the aim of identifying unpublished studies with the potential to address the present research question, we scrutinised retrieved reviews of the impact of childhood state care on related adult health outcomes. All included studies were required to have prospective measurement of state care in childhood and a follow-up of CVD events in adulthood as the primary outcome (incident coronary heart disease and/or stroke). Collaborating investigators provided study-specific estimates which were aggregated using random-effects meta-analysis. The Newcastle-Ottawa Scale was used to assess individual study quality. Findings: Thirteen studies (2 published, 11 unpublished) met the inclusion criteria, and investigators from nine provided viable results, including updated analyses of the published studies. Studies comprised 611,601 individuals (301,129 women) from the US, UK, Sweden, Finland, and Australia. Relative to the unexposed, individuals with a care placement during childhood had a 50% greater risk of CVD in adulthood (summary rate ratio after basic adjustment [95% confidence interval]: 1.50 [1.22, 1.84]); range of study-specific estimates: 1.28 to 2.06; I2 = 69%, p = 0.001). This association was attenuated but persisted after multivariable adjustment for socioeconomic status in childhood (8 studies; 1.41 [1.15, 1.72]) and adulthood (9 studies, 1.28 [1.10, 1.50]). There was a suggestion of a stronger state care-CVD association in women. Interpretation: Our findings show that individuals with experience of state care in childhood have a moderately raised risk of CVD in adulthood. For timely prevention, clinicians and policy makers should be aware that people with a care history may need additional attention in risk factor management.

The Semmelweis Study: a longitudinal occupational cohort study within the framework of the Semmelweis Caring University Model Program for supporting healthy aging.

The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions.