Modifications to residential neighbourhood characteristics and risk of 79 common health conditions: a prospective cohort study.

BACKGROUND: Observational studies have identified a link between unfavourable neighbourhood characteristics and increased risk of morbidity, but it is unclear whether changes in neighbourhoods affect future disease risk. We used a data-driven approach to assess the impact of neighbourhood modification on 79 health outcomes. METHODS: In this prospective cohort study, we used pooled, individual-level data from two Finnish cohort studies: the Health and Social Support study and the Finnish Public Sector study. Neighbourhood characteristics (mean educational level, median income, and employment rate of residents, and neighbourhood green space) and individual lifestyle factors of community-dwelling individuals were assessed at baseline (at different waves starting between 1998 and 2013). We repeated assessment of neighbourhood characteristics and lifestyle factors approximately 5 years from each baseline assessment, after which follow-up began for health conditions diagnosed according to the WHO International Classification of Diseases for 79 common health conditions using linkage to electronic health records. We used Cox proportional hazard regression models to compute adjusted hazard ratios (HRs) of incident disease associated with neighbourhood characteristics and changes in neighbourhood characteristics over time and logistic regression analysis to compute adjusted odds of association between changes in neighbourhood characteristics and individual lifestyle factors. FINDINGS: 114 786 individuals (87 012 [75·8%] women; mean age 44·4 years [SD 11·1]) had complete data and were included in this cohort study. During 1·17 million person-years at risk, we recorded 164 368 new-onset health conditions and 3438 deaths. Favourable changes in neighbourhood characteristics were associated with reduced risk of all-cause mortality and incidence of 19 specific health conditions. Unfavourable changes were correspondingly associated with increased risk of mortality and 27 specific health conditions. Among participants who did not move residence during the observation period, relative to individuals who continually lived in disadvantaged neighbourhoods, those who experienced favourable modifications in neighbourhood characteristics had a lower risk of future diabetes (HR 0·84, 95% CI 0·75-0·93), stroke (0·49, 0·29-0·83), skin disease (0·72, 0·53-0·97), and osteoarthritis (0·87, 0·77-0·99). Living in a neighbourhood with improving characteristics was also associated with improvements in individual-level health-related lifestyle factors. Among participants who lived in advantaged residential environments at baseline, unfavourable changes in neighbourhood characteristics were associated with an increased risk of diabetes, stroke, skin disease, and osteoarthritis compared with individuals who lived in advantaged neighbourhoods throughout the study period. INTERPRETATION: Favourable modifications to residential neighbourhoods showed robust, longitudinal associations with a range of improvements in health outcomes, including improved health behaviours and reduced risk of cardiometabolic, infectious, and orthopaedic conditions. FUNDING: UK Medical Research Council, US National Institute on Aging, NordForsk, and Academy of Finland

Association between change in cardiovascular risk scores and future cardiovascular disease: analyses of data from the Whitehall II longitudinal, prospective cohort study

BACKGROUND: Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40-75 years), is based on risk scores, such as the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk. METHODS: We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models. FINDINGS: 7574 participants (5233 [69·1%] men, 2341 [30·9%] women) aged 40-75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 [72·3%] men and 399 [27·7%] women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 [95% CI 0·000 to 0·008] for SCORE; from 0·699 to 0·700, change 0·001 [0·000 to 0·003] for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change -57 [95% CI -97 to -13] for SCORE; from 14 739 to 14 729, change -10 [-28 to 7] for ASCVD), and the continuous net reclassification index (0·353 [95% CI 0·234 to 0·447] for SCORE; 0·232 [0·030 to 0·344] for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements. INTERPRETATION: Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions. FUNDING: UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging

Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies

Introduction: Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20-year follow-ups. Methods: In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology. Cognitive performance was tested five times over 20 years. Linkage to electronic health records identified incident dementia. The results were replicated in the Atherosclerosis Risk in Communities (ARIC) study. Results: Fifteen non-amyloid/non-tau–related proteins were associated with cognitive decline and dementia, were consistently identified in both cohorts, and were not explained by known dementia risk factors. Levels of six of the proteins are modifiable by currently approved medications for other conditions. Discussion: This study identified several plasma proteins in dementia-free people that are associated with long-term risk of cognitive decline and dementia

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 β −0.34, P<0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted β −0.33, P<0.001), and peptidyl-glycine α-amidating monooxygenase (AMD, fully adjusted β −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

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 1110 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.Copyright (C) 2020 The Author(s). Published by Elsevier Ltd

Modifications to residential neighbourhood characteristics and risk of 79 common health conditions: a prospective cohort study

Background Observational studies have identified a link between unfavourable neighbourhood characteristics and increased risk of morbidity, but it is unclear whether changes in neighbourhoods affect future disease risk. We used a data-driven approach to assess the impact of neighbourhood modification on 79 health outcomes. Methods In this prospective cohort study, we used pooled, individual-level data from two Finnish cohort studies: the Health and Social Support study and the Finnish Public Sector study. Neighbourhood characteristics (mean educational level, median income, and employment rate of residents, and neighbourhood green space) and individual lifestyle factors of community-dwelling individuals were assessed at baseline (at different waves starting between 1998 and 2013). We repeated assessment of neighbourhood characteristics and lifestyle factors approximately 5 years from each baseline assessment, after which follow-up began for health conditions diagnosed according to the WHO International Classification of Diseases for 79 common health conditions using linkage to electronic health records. We used Cox proportional hazard regression models to compute adjusted hazard ratios (HRs) of incident disease associated with neighbourhood characteristics and changes in neighbourhood characteristics over time and logistic regression analysis to compute adjusted odds of association between changes in neighbourhood characteristics and individual lifestyle factors. Findings 114786 individuals (87012 [75.8%] women; mean age 44.4 years [SD 11.1]) had complete data and were included in this cohort study. During 1.17 million person-years at risk, we recorded 164368 new-onset health conditions and 3438 deaths. Favourable changes in neighbourhood characteristics were associated with reduced risk of all-cause mortality and incidence of 19 specific health conditions. Unfavourable changes were correspondingly associated with increased risk of mortality and 27 specific health conditions. Among participants who did not move residence during the observation period, relative to individuals who continually lived in disadvantaged neighbourhoods, those who experienced favourable modifications in neighbourhood characteristics had a lower risk of future diabetes (HR 0.84, 95% CI 0.75-0.93), stroke (0.49, 0. 29-0.83), skin disease (0.72,0.53-0. 97), and osteoarthritis (0.87, 0.77-0.99). Living in a neighbourhood with improving characteristics was also associated with improvements in individual-level health-related lifestyle factors. Among participants who lived in advantaged residential environments at baseline, unfavourable changes in neighbourhood characteristics were associated with an increased risk of diabetes, stroke, skin disease, and osteoarthritis compared with individuals who lived in advantaged neighbourhoods throughout the study period. Interpretation Favourable modifications to residential neighbourhoods showed robust, longitudinal associations with a range of improvements in health outcomes, including improved health behaviours and reduced risk of cardiometabolic, infectious, and orthopaedic conditions. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe