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.

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.

Concurrent changes in physical activity and physical functioning during retirement transition-a multi-trajectory analysis.

BACKGROUND: Physical activity and physical functioning have been reported to change over retirement transition, but the results have been inconsistent, and the two constructs have not been studied concurrently. The objective of this study was to examine concurrent changes in physical activity and physical functioning during transition to retirement among public sector employees, and to examine if occupation, sex, marital status, body mass index (BMI), alcohol consumption and smoking status are associated with observed different multi-trajectory paths. METHODS: 3,550 participants of the Finnish Retirement and Aging study responded to an annual survey on physical activity and physical functioning (SF-36) before and after retirement. Group-based multi-trajectory analysis was used to identify clusters with dissimilar concurrent changes in physical activity and physical functioning. Multinomial regression analysis was used to describe the associations between covariates and the probability of being classified to a certain cluster. RESULTS: Participants were 63.4 (SD 1.4) years old, 83% women, 65% professional workers. Four trajectories of concurrent changes in physical activity and physical functioning were identified, one with decreasing physical functioning and low activity, one with increasing high activity and stable high functioning and two with fluctuating moderate physical activity and stable high functioning. Single, women, obese participants and risk-users of alcohol were more likely to be classified into group with low physical activity and declining physical functioning. CONCLUSIONS: Low physical activity below the level usually recommended was associated with lower physical functioning during retirement transition. These findings could be useful when planning interventions for retirees to maintain their physical functioning level.

Physical activity and self-rated health during retirement transition: a multitrajectory analysis of concurrent changes among public sector employees.

OBJECTIVES: The aim of the study was to evaluate concurrent changes in physical activity and self-rated health during retirement transition over 4 years by multivariate trajectory analysis and to examine whether sociodemographic and lifestyle factors predict the probability of being classified to a certain subgroup of observed changes. DESIGN: Prospective cohort study. SETTING: Public sector employees. PARTICIPANTS: 3550 participants of the Finnish Retirement and Aging study. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants estimated on a yearly questionnaire their weekly hours of different types of activities converted to metabolic equivalent of task-hour/week. Self-rated health was assessed on a 5-point Likert-like scale from poor to excellent and dichotomised as suboptimal and optimal. Multivariate trajectory analysis was used to distinguish different subgroups of trajectories. Multinomial regression analysis was used to describe the associations between covariates and the probability of being classified to a certain trajectory group. RESULTS: Three trajectory groups were identified, all displaying increasing activity during retirement with a simultaneous decrease in perceived suboptimal health. Physical activity peaked at 18 months after retirement and then slightly decreased, except for initially highly physically active participants (9%) with good self-rated health, who demonstrated a constant high level of physical activity. Male gender, professional occupation, being married or cohabiting, body mass index <30 kg/m2, not smoking and using alcohol below risk levels were associated with higher physical activity and better self-rated health. CONCLUSION: Changes in physical activity and perceived health during retirement transition were interconnected. Both were improved during retirement transition, but the change was temporary. Longer follow-up studies are required to assess the changes over a longer period after retirement.

Predicting work disability among people with chronic conditions: a prospective cohort study.

Few risk prediction scores are available to identify people at increased risk of work disability, particularly for those with an existing morbidity. We examined the predictive performance of disability risk scores for employees with chronic disease. We used prospective data from 88,521 employed participants (mean age 43.1) in the Finnish Public Sector Study including people with chronic disorders: musculoskeletal disorder, depression, migraine, respiratory disease, hypertension, cancer, coronary heart disease, diabetes, comorbid depression and cardiometabolic disease. A total of 105 predictors were assessed at baseline. During a mean follow-up of 8.6 years, 6836 (7.7%) participants were granted a disability pension. C-statistics for the 8-item Finnish Institute of Occupational Health (FIOH) risk score, comprising age, self-rated health, number of sickness absences, socioeconomic position, number of chronic illnesses, sleep problems, BMI, and smoking at baseline, exceeded 0.72 for all disease groups and was 0.80 (95% CI 0.80-0.81) for participants with musculoskeletal disorders, 0.83 (0.82-0.84) for those with migraine, and 0.82 (0.81-0.83) for individuals with respiratory disease. Predictive performance was not significantly improved in models with re-estimated coefficients or a new set of predictors. These findings suggest that the 8-item FIOH work disability risk score may serve as a scalable screening tool in identifying individuals with increased risk for work disability.

Association of alcohol use with years lived without major chronic diseases: A multicohort study from the IPD-Work consortium and UK Biobank.

Background: Heavy alcohol consumption increases the risk of several chronic diseases. In this multicohort study, we estimated the number of life-years without major chronic diseases according to different characteristics of alcohol use. Methods: In primary analysis, we pooled individual-level data from up to 129,942 adults across 12 cohort studies with baseline data collection on alcohol consumption, drinking patterns, and history between 1986 and 2005 (the IPD-Work Consortium). Self-reported alcohol consumption was categorised according to UK guidelines - non-drinking (never or former drinkers); moderate consumption (1-14 units); heavy consumption (>14 units per week). We further subdivided moderate and heavy drinkers by binge drinking pattern (alcohol-induced loss of consciousness). In addition, we assessed problem drinking using linked data on hospitalisations due to alcohol abuse or poisoning. Follow-up for chronic diseases for all participants included incident type 2 diabetes, coronary heart disease, stroke, cancer, and respiratory disease (asthma and chronic obstructive pulmonary disease) as ascertained via linkage to national morbidity and mortality registries, repeated medical examinations, and/or self-report. We estimated years lived without any of these diseases between 40 and 75 years of age according to sex and characteristics of alcohol use. We repeated the main analyses using data from 427,621 participants in the UK Biobank cohort study. Findings: During 1·73 million person-years at risk, 22,676 participants in IPD-Work cohorts developed at least one chronic condition. From age 40 to 75 years, never-drinkers [men: 29·3 (95%CI 27·9-30·8) years, women 29·8 (29·2-30·4) years)] and moderate drinkers with no binge drinking habit [men 28·7 (28·4-29·0) years, women 29·6 (29·4-29·7) years] had the longest disease-free life span. A much shorter disease-free life span was apparent in participants who experienced alcohol poisoning [men 23·4 (20·9-26·0) years, women 24·0 (21·4-26·5) years] and those with self-reported heavy overall consumption and binge drinking [men: 26·0 (25·3-26·8), women 27·5 (26·4-28·5) years]. The pattern of results for alcohol poisoning and self-reported alcohol consumption was similar in UK Biobank. In IPD-Work and UK Biobank, differences in disease-free years between self-reported moderate drinkers and heavy drinkers were 1·5 years or less. Interpretation: Individuals with alcohol poisonings or heavy self-reported overall consumption combined with a binge drinking habit have a marked 3- to 6-year loss in healthy longevity. Differences in disease-free life between categories of self-reported weekly alcohol consumption were smaller. Funding: Medical Research Council, National Institute on Aging, NordForsk, Academy of Finland, Finnish Work Environment Fund.

Persistence of sleep difficulties for over 16 years amongst 66,948 working-aged adults.

The objective was to investigate the persistence of sleep difficulties for over 16 years amongst a population of working age. In this prospective cohort study, a group-based trajectory analysis of repeated surveys amongst 66,948 employees in public sector (mean age 44.7 [SD 9.4] years, 80% women) was employed. The main outcome measure was sleep difficulties based on Jenkins Sleep Scale (JSS). Up to 70% of the respondents did not experience sleep difficulties whereas up to 4% reported high frequency of notable sleep difficulties through the entire 16-year follow-up. Heavy drinking predicted sleep difficulties (OR 2.3 95% CI 1.6 to 3.3) except for the respondents younger than 40 years. Smoking was associated with sleep difficulties amongst women younger than 40 years (OR 1.2, 95% CI 1.0 to 1.5). Obesity was associated with sleep difficulties amongst men (OR 1.9, 95% CI 1.4 to 2.7) and women (OR 1.2, 95% CI 1.1 to 1.3) of middle age and amongst women older than 50 (OR 1.5, 95% CI 1.2 to 1.8) years. Physical inactivity predicted sleep difficulties amongst older men (OR 1.3, 95% CI 1.1 to 1.6). In this working-age population, sleep difficulties showed a great persistence over time. In most of the groups, the level of sleep difficulties during the follow-up was almost solely dependent on the level of initial severity. Depending on sex and age, increasing sleep problems were sometimes associated with high alcohol consumption, smoking, obesity and physical inactivity, but the strength of these associations varied.

Association of changes in lifestyle with changes in sleep difficulties: an analysis of 38 400 participants over a 16-year follow-up.

OBJECTIVES: To investigate the association between changes in lifestyle risk factors and changes is sleep difficulties. DESIGN: Longitudinal repeated measures cohort study. SETTING: University and national institute of occupational health. PARTICIPANTS: Participants of the Finnish Public Sector study with information on sleep and lifestyle-related risk factors collected in five repeat surveys with 4-year intervals from 2000 to 2017. The participants were those, who had responded at least twice and had a change in sleep difficulties (having sleep difficulties vs not) (142 969 observations from 38 400 respondents (mean age 45.5 (SD 9.2) years, 83% women). PRIMARY AND SECONDARY OUTCOME MEASURES: Changes in sleep quality over time. Longitudinal fixed effects analysis, a method that accounts for time-invariant confounders by design, was used. RESULTS: At first available response, sleep difficulties were experienced by 13 998 (36%) of the respondents. Respectively, the mean age was 44.3 (10.0) years, 7526 (20%) were obese, 13 487 (35%) reported low physical activity, 3338 (9%) extensively drinking and 6547 (17%) were smoking. Except for smoking, the changes in the studied modifiable risks were associated with changes in sleep difficulties. The ORs for having sleep difficulties were 1.41 (95% CI 1.35 to 1.48) for obesity, 1.10 (95% CI 1.06 to 1.13) for low physical activity and 1.43 (95% CI 1.35 to 1.51) for heavy drinking. For smoking, the association was negative with OR 0.81 (95% CI 0.76 to 0.86). Including all four modifiable risks into model changed the estimates only little. CONCLUSIONS: The results of this longitudinal study suggest that changes in sleep quality are interconnected with changes in lifestyle.

Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies.

OBJECTIVES: To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. DESIGN: Multicohort study with three sets of analyses. SETTING: United Kingdom, Europe, and the United States. PARTICIPANTS: Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. MAIN OUTCOME MEASURES: Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. RESULTS: During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted ß -0.34, P<0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted ß -0.33, P<0.001), and peptidyl-glycine α-amidating monooxygenase (AMD, fully adjusted ß -0.32, P<0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD. CONCLUSIONS: The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that cognitive stimulation is associated with lower levels of plasma proteins that potentially inhibit axonogenesis and synaptogenesis and increase the risk of dementia might provide clues to underlying biological mechanisms.

Daily Physical Activity Patterns and Their Association With Health-Related Physical Fitness Among Aging Workers-The Finnish Retirement and Aging Study.

BACKGROUND: This study aimed to identify accelerometer-measured daily physical activity patterns, and to examine how they associate with health-related physical fitness among aging workers. METHODS: The study population consisted of 263 participants (mean age 62.4 years, SD 1.0) from the Finnish Retirement and Aging study, who used wrist-worn ActiGraph accelerometer for at least 1 week including both workdays and days off. Health-related physical fitness measures included body composition (waist circumference, bioimpedance), cardiorespiratory fitness (bicycle ergometer test), and muscular fitness (push-up and chair rise tests). RESULTS: Based on the latent class trajectory analysis, 6 trajectories were identified for workdays showing variation in activity level on working hours and on evening hours. Moderate activity during working hours and increase of activity level in the evening was associated with the most favorable health-related fitness in comparison to low activity throughout the workday: waist circumference 90.0 cm (95% confidence interval [CI] 85.5-94.5) versus 99.5 cm (95% CI 96.8-102.3), fat mass 13.9 kg (9.3-18.5) versus 23.8 kg (20.2-27.4), cardiorespiratory fitness 33.4 mL/kg/min (95% CI 31.4-35.3) versus 29.1 mL/kg/min (95% CI 27.8-30.3) (adjusted for age, sex, days off activity, smoking, and alcohol). For the days off, 2 different trajectories were identified, but they differed only in terms of level and not by timing of physical activity. CONCLUSIONS: A large variation in the workday physical activity patterns was observed among aging workers. Independent of worktime activity, people who were more active in the evenings had more favorable health-related physical fitness than those who were less active throughout the day.

Long-term risk of dementia following hospitalization due to physical diseases: A multicohort study.

INTRODUCTION: Conventional risk factors targeted by prevention (e.g., low education, smoking, and obesity) are associated with a 1.2- to 2-fold increased risk of dementia. It is unclear whether having a physical disease is an equally important risk factor for dementia. METHODS: In this exploratory multicohort study of 283,414 community-dwelling participants, we examined 22 common hospital-treated physical diseases as risk factors for dementia. RESULTS: During a median follow-up of 19 years, a total of 3416 participants developed dementia. Those who had erysipelas (hazard ratio = 1.82; 95% confidence interval = 1.53 to 2.17), hypothyroidism (1.94; 1.59 to 2.38), myocardial infarction (1.41; 1.20 to 1.64), ischemic heart disease (1.32; 1.18 to 1.49), cerebral infarction (2.44; 2.14 to 2.77), duodenal ulcers (1.88; 1.42 to 2.49), gastritis and duodenitis (1.82; 1.46 to 2.27), or osteoporosis (2.38; 1.75 to 3.23) were at a significantly increased risk of dementia. These associations were not explained by conventional risk factors or reverse causation. DISCUSSION: In addition to conventional risk factors, several physical diseases may increase the long-term risk of dementia.

Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases.

Importance: It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown. Objective: To estimate the association between healthy lifestyle and the number of disease-free life-years. Design, Setting, and Participants: A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020. Exposures: Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors. Main Outcomes and Measures: The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease. Results: Of the 116 043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex. Conclusions and Relevance: In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.

Job Strain as a Risk Factor for Peripheral Artery Disease: A Multi-Cohort Study.

Background Job strain is implicated in many atherosclerotic diseases, but its role in peripheral artery disease (PAD) is unclear. We investigated the association of job strain with hospital records of PAD, using individual-level data from 11 prospective cohort studies from Finland, Sweden, Denmark, and the United Kingdom. Methods and Results Job strain (high demands and low control at work) was self-reported at baseline (1985-2008). PAD records were ascertained from national hospitalization data. We used Cox regression to examine the associations of job strain with PAD in each study, and combined the study-specific estimates in random effects meta-analyses. We used τ2, I2, and subgroup analyses to examine heterogeneity. Of the 139 132 participants with no previous hospitalization with PAD, 32 489 (23.4%) reported job strain at baseline. During 1 718 132 person-years at risk (mean follow-up 12.8 years), 667 individuals had a hospital record of PAD (3.88 per 10 000 person-years). Job strain was associated with a 1.41-fold (95% CI, 1.11-1.80) increased average risk of hospitalization with PAD. The study-specific estimates were moderately heterogeneous (τ2=0.0427, I2: 26.9%). Despite variation in their magnitude, the estimates were consistent in both sexes, across the socioeconomic hierarchy and by baseline smoking status. Additional adjustment for baseline diabetes mellitus did not change the direction or magnitude of the observed associations. Conclusions Job strain was associated with small but consistent increase in the risk of hospitalization with PAD, with the relative risks on par with those for coronary heart disease and ischemic stroke.

Association between socioeconomic status and the development of mental and physical health conditions in adulthood: a multi-cohort study.

BACKGROUND: Socioeconomic disadvantage is a risk factor for many diseases. We characterised cascades of these conditions by using a data-driven approach to examine the association between socioeconomic status and temporal sequences in the development of 56 common diseases and health conditions. METHODS: In this multi-cohort study, we used data from two Finnish prospective cohort studies: the Health and Social Support study and the Finnish Public Sector study. Our pooled prospective primary analysis data comprised 109 246 Finnish adults aged 17-77 years at study entry. We captured socioeconomic status using area deprivation and education at baseline (1998-2013). Participants were followed up for health conditions diagnosed according to the WHO International Classification of Diseases until 2016 using linkage to national health records. We tested the generalisability of our findings with an independent UK cohort study-the Whitehall II study (9838 people, baseline in 1997, follow-up to 2017)-using a further socioeconomic status indicator, occupational position. FINDINGS: During 1 110 831 person-years at risk, we recorded 245 573 hospitalisations in the Finnish cohorts; the corresponding numbers in the UK study were 60 946 hospitalisations in 186 572 person-years. Across the three socioeconomic position indicators and after adjustment for lifestyle factors, compared with more advantaged groups, low socioeconomic status was associated with increased risk for 18 (32·1%) of the 56 conditions. 16 diseases formed a cascade of inter-related health conditions with a hazard ratio greater than 5. This sequence began with psychiatric disorders, substance abuse, and self-harm, which were associated with later liver and renal diseases, ischaemic heart disease, cerebral infarction, chronic obstructive bronchitis, lung cancer, and dementia. INTERPRETATION: Our findings highlight the importance of mental health and behavioural problems in setting in motion the development of a range of socioeconomically patterned physical illnesses. Policy and health-care practice addressing psychological health issues in social context and early in the life course could be effective strategies for reducing health inequalities. FUNDING: UK Medical Research Council, US National Institute on Aging, NordForsk, British Heart Foundation, Academy of Finland, and Helsinki Institute of Life Science.

Lifestyle Changes in Relation to Initiation of Antihypertensive and Lipid-Lowering Medication: A Cohort Study.

Background Lifestyle modification is a key component of cardiovascular disease prevention before and concurrently with pharmacologic interventions. We evaluated whether lifestyle factors change in relation to the initiation of antihypertensive or lipid-lowering medication (statins). Methods and Results The study population comprised 41 225 participants of the FPS (Finnish Public Sector) study aged ≥40 years who were free of cardiovascular disease at baseline and responded to ≥2 consecutive surveys administered in 4-year intervals in 2000-2013. Medication use was ascertained through pharmacy-claims data. Using a series of pre-post data sets, we compared changes in body mass index, physical activity, alcohol consumption, and smoking between 8837 initiators and 46 021 noninitiators of antihypertensive medications or statins. In participants who initiated medication use, body mass index increased more (difference in change 0.19; 95% CI, 0.16-0.22) and physical activity declined (-0.09 metabolic equivalent of task hour/day; 95% CI, -0.16 to -0.02) compared with noninitiators. The likelihood of becoming obese (odds ratio: 1.82; 95% CI, 1.63-2.03) and physically inactive (odds ratio: 1.08; 95% CI, 1.01-1.17) was higher in initiators. However, medication initiation was associated with greater decline in average alcohol consumption (-1.85 g/week; 95% CI, -3.67 to -0.14) and higher odds of quitting smoking (odds ratio for current smoking in the second survey: 0.74; 95% CI, 0.64-0.85). Conclusions These findings suggest that initiation of antihypertensive and statin medication is associated with lifestyle changes, some favorable and others unfavorable. Weight management and physical activity should be encouraged in individuals prescribed these medications.

Diet quality as a predictor of cardiometabolic disease-free life expectancy: the Whitehall II cohort study.

BACKGROUND: Poor diet quality has been linked to increased risk of many chronic diseases and premature mortality. Less research has considered dietary habits in relation to disease-free life expectancy. OBJECTIVES: Our objective was to investigate the association of diet quality with cardiometabolic disease-free life expectancy between ages 50 and 85 y. METHODS: Diet quality of 8041 participants of the Whitehall II cohort study was assessed with the Alternative Healthy Eating Index 2010 (AHEI-2010) in 1991-1994, 1997-1999, and 2002-2004. The measurement of diet quality closest to age 50 for each participant was used. We utilized repeat measures of cardiometabolic disease (coronary heart disease, stroke, and type 2 diabetes) from the first observation when participants were aged ≥50 y. Multistate life table models with covariates age, gender, occupational position, smoking, physical activity, and alcohol consumption were used to estimate total and sex-specific cardiometabolic disease-free life expectancy from age 50 to 85 y for each AHEI-2010 quintile, where the lowest quintile represents unhealthiest dietary habits and the highest quintile the healthiest habits. RESULTS: The number of cardiometabolic disease-free life-years after age 50 was 23.9 y (95% CI: 23.0, 24.9 y) for participants with the healthiest diet, that is, a higher score on the AHEI-2010, and 21.4 y (95% CI: 20.6, 22.3 y) for participants with the unhealthiest diet. The association between diet quality and cardiometabolic disease-free life expectancy followed a dose-response pattern and was observed in subgroups of participants of different occupational position, BMI, physical activity level, and smoking habit, as well as when participants without cardiometabolic disease at baseline were excluded from analyses. CONCLUSIONS: Healthier dietary habits are associated with cardiometabolic disease-free life expectancy between ages 50 and 85.

Commuting time to work and behaviour-related health: a fixed-effect analysis.

OBJECTIVES: Long commuting times are linked to poor health outcomes, but the evidence is mainly cross-sectional. We examined longitudinal within-individual associations between commuting time and behaviour-related health. METHODS: Data were from the Swedish Longitudinal Occupational Survey of Health study. We selected workers who responded to a minimum of two surveys conducted every other year between 2008 and 2018. We included all study waves with self-reported commuting time (ie, the exposure, 1-5, 6-10, 11-15 or ≥15 hours/week), body mass index (based on weight and height), physical (in)activity, smoking, alcohol use and sleep problems (ie, the outcomes) (Nindividuals=20 376, Nobservations=46 169). We used conditional logistic regression for fixed effects analyses that controls for time-varying confounders by design. Analyses were stratified by working hours: normal (30-40 hours/week) or longer than normal (>40 hours/week) and adjusted for time dependent covariates: age, marital status, occupational position, presence of children, chronic disease, depressive symptoms, job strain and shift work. RESULTS: Those working >40 hours/week had higher odds of physical inactivity (OR 1.25, 95% CI 1.03 to 1.51) and sleep problems (OR 1.16, 95% CI 1.00 to 1.35) when they were commuting >5 hours/week than when they were commuting 1-5 hours/week. Among women working normal hours, longer commuting time associated with lower odds of problem drinking. CONCLUSION: Our findings suggest that lengthy commuting time increases the risk of physical inactivity and sleep problems if individuals have longer than normal weekly working hours. Effects of work arrangements that decrease commuting time should be examined in relation to health behaviours.

Association between adverse childhood experiences and adult diseases in older adults: a comparative cross-sectional study in Japan and Finland.

OBJECTIVE: We aimed to examine the association between adverse childhood experiences (ACEs) and diseases in older adults in Japan and Finland. DESIGN: Cross-sectional comparative study. SETTING: Data from a gerontological study in Japan and two public health studies in Finland were evaluated. PARTICIPANTS: A total of 13 123 adults (mean age, 69.5 years) from Japan and 10 353 adults (mean age, 64.4 years) from Finland were included in this study. Logistic regression was used to examine the association of each of, any of and the cumulative number of ACEs (parental divorce, fear of a family member and poverty in childhood; treated as ordered categorical variables) with poor self-rated health (SRH), cancer, heart disease or stroke, diabetes mellitus, smoking and body mass index. Models were adjusted for sex, age, education, marital status and working status. RESULTS: Of the respondents, 50% of those in Japan and 37% of those in Finland reported having experienced at least one of the measured ACEs. Number of ACEs was associated with poor SRH in both countries, and the point estimates were similar (OR: 1.35, 95% CI: 1.25 to 1.46 in Japan; OR: 1.34, 95% CI: 1.27 to 1.41 in Finland). Number of ACEs was associated with the prevalence of cancer, heart disease or stroke, diabetes mellitus, current smoking and an increase in body mass index in both countries. CONCLUSIONS: The association between ACEs and poor SRH, adult diseases and health behaviours was similar among older adults in both Japan and Finland. This international comparative study suggests that the impact of ACEs on health is noteworthy and consistent across cultural and social environments.

5-year versus risk-category-specific screening intervals for cardiovascular disease prevention: a cohort study.

BACKGROUND: Clinical guidelines suggest preventive interventions such as statin therapy for individuals with a high estimated 10-year risk of major cardiovascular events. For those with a low or intermediate estimated risk, risk-factor screenings are recommended at 5-year intervals; this interval is based on expert opinion rather than on direct research evidence. Using longitudinal data on the progression of cardiovascular disease risk over time, we compared different screening intervals in terms of timely detection of high-risk individuals, cardiovascular events prevented, and health-care costs. METHODS: We used data from participants in the British Whitehall II study (aged 40-64 years at baseline) who had repeated biomedical screenings at 5-year intervals and linked these data to electronic health records between baseline (Aug 7, 1991, to May 10, 1993) and June 30, 2015. We estimated participants' 10-year risk of a major cardiovascular event (myocardial infarction, cardiac death, and fatal or non-fatal stroke) using the revised Atherosclerotic Cardiovascular Disease (ASCVD) calculator. We used multistate Markov modelling to estimate optimum screening intervals on the basis of progression rates from low-risk and intermediate-risk categories to the high-risk category (ie, ≥7·5% 10-year risk of a major cardiovascular event). Our assessment criteria included person-years spent in a high-risk category before detection, the number of major cardiovascular events prevented and quality-adjusted life-years (QALYs) gained, and screening costs. FINDINGS: Of 6964 participants (mean age 50·0 years [SD 6·0] at baseline) with 152 700 person-years of follow-up (mean follow-up 22·0 years [SD 5·0]), 1686 participants progressed to the high-risk category and 617 had a major cardiovascular event. With the 5-year screening intervals, participants spent 7866 (95% CI 7130-8658) person-years unrecognised in the high-risk group. For individuals in the low, intermediate-low, and intermediate-high risk categories, 21 alternative risk category-based screening intervals outperformed the 5-yearly screening protocol. Screening intervals at 7 years, 4 years, and 1 year for those in the low, intermediate-low, and intermediate-high-risk category would reduce the number of person-years spent unrecognised in the high-risk group by 62% (95% CI 57-66; 4894 person-years), reduce the number of major cardiovascular events by 8% (7-9; 49 events), and raise 44 QALYs (40-49) for the study population. INTERPRETATION: In terms of timely preventive interventions, the 5-year screening intervals were unnecessarily frequent for low-risk individuals and insufficiently frequent for intermediate-risk individuals. Screening intervals based on risk-category-specific progression rates would perform better in terms of preventing major cardiovascular disease events and improving cost-effectiveness. FUNDING: Medical Research Council, British Heart Association, National Institutes on Aging, NordForsk, Academy of Finland.

The effect of smoking cessation on work disability risk: a longitudinal study analysing observational data as non-randomized nested pseudo-trials.

BACKGROUND: Smoking increases disability risk, but the extent to which smoking cessation reduces the risk of work disability is unclear. We used non-randomized nested pseudo-trials to estimate the benefits of smoking cessation for preventing work disability. METHODS: We analysed longitudinal data on smoking status and work disability [long-term sickness absence (≥90 days) or disability pension] from two independent prospective cohort studies-the Finnish Public Sector study (FPS) (n = 7393) and the Health and Social Support study (HeSSup) (n = 2701)-as 'nested pseudo-trials'. All the 10 094 participants were smokers at Time 1 and free of long-term work disability at Time 2. We compared the work disability risk after Time 2 of the participants who smoked at Time 1 and Time 2 with that of those who quit smoking between these times. RESULTS: Of the participants in pseudo-trials, 2964 quit smoking between Times 1 and 2. During the mean follow-up of 4.8 to 8.6 years after Time 2, there were 2197 incident cases of work disability across the trials. Quitting smoking was associated with a reduced risk of any work disability [summary hazard ratio = 0.89, 95% confidence interval (CI) 0.81-0.98]. The hazard ratio for the association between quitting smoking and permanent disability pension (928 cases) was of similar magnitude, but less precisely estimated (0.91, 95% CI 0.81-1.02). Among the participants with high scores on the work disability risk score (top third), smoking cessation reduced the risk of disability pension by three percentage points. Among those with a low risk score (bottom third), smoking cessation reduced the risk by half a percentage point. CONCLUSIONS: Our results suggest an approximately 10% hazard reduction of work disability as a result of quitting smoking.