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Competing Interests: We are both involved in programmes to develop Marmot Places and are Director (MM) and Deputy Director (JA) of the Institute of Health Equity (IHE) that is working with collaborators on Marmot Places. Funding for IHE comes from University College London and the places that commission us to advise them. IHE is one of the academic centres collaborating in the WHO Special Initiative. We declare no other competing interests.

Mental disorders account for at least 18% of global disease burden, and the associated annual global costs are projected to be US$6 trillion by 2030. Evidence-based, cost-effective public mental health (PMH) interventions exist to prevent mental disorders from arising, prevent associated impacts of mental disorders (including through treatment), and promote mental wellbeing and resilience. However, only a small proportion of people with mental disorders receive minimally adequate treatment. Compared with treatment, there is even less coverage of interventions to prevent the associated impacts of mental disorders, prevent mental disorders from arising, or promote mental wellbeing and resilience. This implementation failure breaches the right to health, has increased during the COVID-19 pandemic, and results in preventable suffering, broad impacts, and associated economic costs. In this Health Policy paper, we outline specific actions to improve the coverage of PMH interventions, including PMH needs assessments, collaborative advocacy and leadership, PMH practice to inform policy and implementation, training and improvement of population literacy, settings-based and integrated approaches, use of digital technology, maximising existing resources, focus on high-return interventions, human rights approaches, legislation, and implementation research. Increased interest in PMH in populations and governments since the onset of the COVID-19 pandemic supports these actions. Improved implementation of PMH interventions can result in broad health, social, and economic impacts, even in the short-term, which support the achievement of a range of policy objectives, sustainable economic development, and recovery., Competing Interests: Declaration of interests AJ, MM, PU, CL, SS, JC, and JA are members of the Public Mental Health Working Group for the World Psychiatric Association's 2020–2023 Action Plan. JC has contributed to national policy in England, has done mental health needs assessments for local authorities in England (for which his employer received payment); is strategic and clinical director of the Royal College of Psychiatrist's Public Mental Health Implementation Centre; and is a public mental health advisor to WHO Europe. CL has received research funding from the UK Department for International Development, UK National Institute for Health Research, US National Institute of Mental Health, UK Economic and Social Research Council, European Commission, the Wellcome Trust, and Prudential Africa. NS has received honoraria for lectures from the Lundbeck company and from several universities. JA has contributed to national and state policy and service development in his role as a senior public servant., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1β and tumor necrosis factor α- in 6 European cohort studies., Methods: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation., Results: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1β and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated with higher inflammation even after adjusting for health behaviours and body mass index. No association was found with interleukin 1β and tumor necrosis factor α., Conclusions: Our study suggests different educational patterning of inflammatory biomarkers. Further large-scale research is needed to explore social differences in the inflammatory cascade in greater detail and the extent to which these differences contribute to social inequalities in health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease., Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies., Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively., Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines., Funding: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors., Methods: We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors., Findings: During 26·6 million person-years at risk (mean follow-up 13·3 years [SD 6·4 years]), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98-1·11) for obesity in men and 2 ·17 (2·06-2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38-1·45 for men; 1·34, 1·28-1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21-1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking., Interpretation: Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality., Funding: European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Social inequalities are a proper concern of epidemiology. Epidemiological thinking and modes of analysis are central, but epidemiological research is one among many areas of study that provide the evidence for understanding the causes of social inequalities in health and what can be done to reduce them. Understanding the causes of health inequalities requires insights from social, behavioral and biological sciences, and a chain of reasoning that examines how the accumulation of positive and negative influences over the life course leads to health inequalities in adult life. Evidence that the social gradient in health can be reduced should make us optimistic that reducing health inequalities is a realistic goal for all societies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target., Methods: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis., Findings: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials)., Interpretation: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition., Funding: The funding sources are cited at the end of the paper., (Copyright © 2015 Swerdlow et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

We examined whether relative occupational social class inequalities in physical health functioning widen, narrow or remain stable among white collar employees from three affluent countries. Health functioning was assessed twice in occupational cohorts from Britain (1997-1999 and 2003-2004), Finland (2000-2002 and 2007) and Japan (1998-1999 and 2003). Widening inequalities were seen for British and Finnish men, whereas inequalities among British and Finnish women remained relatively stable. Japanese women showed reverse inequalities at follow up, but no health inequalities were seen among Japanese men. Health behaviours and social relations explained 4-37% of the magnitude in health inequalities, but not their widening., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In most countries, people who have a low socioeconomic status and those who live in poor or marginalised communities have a higher risk of dying from non-communicable diseases (NCDs) than do more advantaged groups and communities. Smoking rates, blood pressure, and several other NCD risk factors are often higher in groups with low socioeconomic status than in those with high socioeconomic status; the social gradient also depends on the country's stage of economic development, cultural factors, and social and health policies. Social inequalities in risk factors account for more than half of inequalities in major NCDs, especially for cardiovascular diseases and lung cancer. People in low-income countries and those with low socioeconomic status also have worse access to health care for timely diagnosis and treatment of NCDs than do those in high-income countries or those with higher socioeconomic status. Reduction of NCDs in disadvantaged groups is necessary to achieve substantial decreases in the total NCD burden, making them mutually reinforcing priorities. Effective actions to reduce NCD inequalities include equitable early childhood development programmes and education; removal of barriers to secure employment in disadvantaged groups; comprehensive strategies for tobacco and alcohol control and for dietary salt reduction that target low socioeconomic status groups; universal, financially and physically accessible, high-quality primary care for delivery of preventive interventions and for early detection and treatment of NCDs; and universal insurance and other mechanisms to remove financial barriers to health care., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies., Methods: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death., Findings: 30,214 (15%) of 197,473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%., Interpretation: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking., Funding: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The European region has seen remarkable heath gains in those populations that have experienced progressive improvements in the conditions in which people are born, grow, live, and work. However, inequities, both between and within countries, persist. The review reported here, of inequities in health between and within countries across the 53 Member States of the WHO European region, was commissioned to support the development of the new health policy framework for Europe: Health 2020. Much more is understood now about the extent, and social causes, of these inequities, particularly since the publication in 2008 of the report of the Commission on Social Determinants of Health. The European review builds on the global evidence and recommends policies to ensure that progress can be made in reducing health inequities and the health divide across all countries, including those with low incomes. Action is needed--on the social determinants of health, across the life course, and in wider social and economic spheres--to achieve greater health equity and protect future generations., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: There is mixed evidence that socioeconomic status (SES) affects the predictive power of self-rated health (SRH) for mortality. We sought to compare the predictive value of SRH for 6-year mortality in English and Brazilian older adults, and to assess whether this association varies by SES in these populations., Methods: Data came from the English and the Bambui (Brazil) cohort studies of aging. Potential confounding variables included sociodemographic characteristics, lifestyle, self-reported diseases, physical functioning, mental symptoms, and selected biomarker measures., Results: Participants were 5183 English and 1499 Brazilians aged 60 years and over. Low health ratings were independently associated with subsequent mortality in both populations. However, the predictive power of poor SRH for death was much higher for English (a population with higher SES level) than for Brazilians (adjusted hazard ratios 4.45 [95% confidence interval, 3.04-6.51] and 1.88 [1.25-2.81], respectively). In both populations, the predictive value of SRH for mortality was higher among those in the highest income tertile., Conclusions: Our results suggest that the association between SRH and mortality is underestimated in populations and in subgroups of population with low SES level. Further international research is needed to examine the generalizability of this pattern., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The health of adolescents is strongly affected by social factors at personal, family, community, and national levels. Nations present young people with structures of opportunity as they grow up. Since health and health behaviours correspond strongly from adolescence into adult life, the way that these social determinants affect adolescent health are crucial to the health of the whole population and the economic development of nations. During adolescence, developmental effects related to puberty and brain development lead to new sets of behaviours and capacities that enable transitions in family, peer, and educational domains, and in health behaviours. These transitions modify childhood trajectories towards health and wellbeing and are modified by economic and social factors within countries, leading to inequalities. We review existing data on the effects of social determinants on health in adolescence, and present findings from country-level ecological analyses on the health of young people aged 10-24 years. The strongest determinants of adolescent health worldwide are structural factors such as national wealth, income inequality, and access to education. Furthermore, safe and supportive families, safe and supportive schools, together with positive and supportive peers are crucial to helping young people develop to their full potential and attain the best health in the transition to adulthood. Improving adolescent health worldwide requires improving young people's daily life with families and peers and in schools, addressing risk and protective factors in the social environment at a population level, and focusing on factors that are protective across various health outcomes. The most effective interventions are probably structural changes to improve access to education and employment for young people and to reduce the risk of transport-related injury., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown., Methods: Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis., Findings: In 40 studies including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34-10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31-9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60-1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25,458 coronary heart disease cases and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93-0·97, p=1·53×10(-5))., Interpretation: On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses., Funding: UK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Health inequalities are present throughout the world, both within and between countries. The Commission on Social Determinants of Health drew attention to dramatic social gradients in health within most countries and made proposals for action. These inequalities are not inevitable. The purpose of this article is to report on activity that has taken place worldwide after the report by the Commission on Social Determinants of Health. First, we summarise the global situation. Second, we summarise an interim report of the emerging findings from an independent review of social determinants and the health divide, which was commissioned by the WHO European region. The world conference on social determinants of health will be held in Rio de Janeiro, Brazil, in October, 2011. This summit provides an opportunity to galvanise support, prioritise action, and respond to the call by the Commission on Social Determinants of Health for social justice as a route to a fair distribution of health., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Low socioeconomic status (SES) may be associated with accelerated biological aging, but findings relating SES with telomere length have been inconsistent. We tested the hypotheses that shorter telomere length and telomerase activity would be related more robustly to education, an early life indicator of socioeconomic position, than to current indicators of socioeconomic circumstances. Healthy men and women aged 53-76 years from the Whitehall II epidemiological cohort provided blood samples from which telomere length was assessed in 448 and telomerase activity in 416. Educational attainment was classified into four levels, while household income and grade of employment were measured as indicators of current socioeconomic circumstances. Age, gender, blood pressure, glycated hemoglobin, high density lipoprotein cholesterol, smoking, body mass index and physical activity were included as covariates. We found that lower educational attainment was associated with shorter telomere length after controlling statistically for biological and behavioral covariates. Neither household income nor employment grade was related to telomere length. The association between telomere length and education remained significant after adjusting for current socioeconomic circumstances. In men, highest levels of telomerase activity were found in the lowest education group. We conclude that low SES defined in terms of education but not current socioeconomic circumstances is associated with shortened telomeres. Low educational attainment may be an indicator of long-term SES trajectories, and be associated with accumulated allostatic load resulting in telomere shortening. Education may also promote problem-solving skills leading to reduced biological stress responsivity, with favorable consequences for biological aging., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Indexes of diet quality have been shown to be associated with decreased risk of mortality in several countries. It remains unclear if the Alternative Healthy Eating Index (AHEI), designed to provide dietary guidelines to combat major chronic diseases, is related to mortality risk., Objective: We aimed to examine the association between adherence to the AHEI and cause-specific mortality over 18 y of follow-up in a British working population., Design: Analyses are based on 7319 participants (mean age: 49.5 y; range: 39-63 y; 30.3% women) from the Whitehall II Study. Cox proportional hazards regression models were performed to analyze associations of the AHEI (scored on the basis of intake of 9 components: vegetables, fruit, nuts and soy, white or red meat, trans fat, polyunsaturated or saturated fat, fiber, multivitamin use, and alcohol) with mortality risk., Results: After potential confounders were controlled for, participants in the top compared with the bottom third of the AHEI score showed 25% lower all-cause mortality [hazard ratio (HR): 0.76; 95% CI: 0.61, 0.95] and >40% lower mortality from cardiovascular disease (CVD; HR: 0.58; 95% CI: 0.37, 0.91). Consumption of nuts and soy and moderate alcohol intake appeared to be the most important independent contributors to decreased mortality risk. The AHEI was not associated with cancer mortality or noncancer/non-CVD mortality., Conclusion: Our findings suggest that the encouragement of adherence to the AHEI dietary recommendations constitutes a valid and clear public health recommendation that would decrease the risk of premature death from CVD.

Background: We examined socioeconomic and ethnic differences in use of lipid-lowering drugs after deregulation of simvastatin in the UK for adults with moderate or high risk of coronary heart disease., Methods: 3631 participants in the Whitehall II cohort study (mean age 62.7 years, 91% white) were informed of their risk of coronary heart disease, based on Framingham score, before deregulation (2002-2004). The use of prescribed lipid-lowering drugs and use of over-the-counter simvastatin were analysed as outcome variables, after deregulation (2005-2007)., Results: 2451 participants were at high risk and 1180 at moderate risk. 20% moderate-risk and 44% high-risk participants reported using prescribed lipid-lowering drugs although no over-the-counter simvastatin was used. Prescribing rates did not differ between employment grades (an index of socioeconomic position), but was higher among South Asian high-risk compared with White high-risk participants (odds ratio 1.64, 95% CI 1.21-2.23). Of the high-risk participants, 44% recalled their increased coronary heart disease risk. South Asian high-risk participants were less likely to recall than White high-risk participants (odds ratio 0.65, 95% CI 0.46-0.93). Furthermore, high risk participants with middle (odds ratio 0.74, 95% CI 0.61-0.89) and low (odds ratio 0.52, 95% CI 0.37-0.74) employment grades were less likely to recall than those with high grades., Conclusion: Socioeconomic and ethnic differences in reported use of lipid-lowering drugs were small, but the use of these drugs in general was much lower than recommended and the participants did not utilise over-the-counter statins. Ethnic minorities and lower socioeconomic position groups were less likely to be aware of their increased coronary risk., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The use of anti-depressant medication has been linked to cardiovascular disease (CVD). We examined the association between anti-depressant medication use and a marker of low grade systemic inflammation as a potential pathway linking anti-depressant use and CVD in two population based studies. Data were collected in a representative sample of 8131 community dwelling adults (aged 47.4±15.9 years, 46.7% male) from the Scottish Health Surveys (SHS). The use of anti-depressant medication was coded according to the British National Formulary and blood was drawn for the measurement of C-reactive protein (CRP). In a second study, we attempted to replicate our findings using longitudinal data from the Whitehall II study (n=4584, aged 55.5±5.9 years, mean follow-up 5.5 years). Antidepressants were used in 5.6% of the SHS sample, with selective serotonin reuptake inhibitors (SSRIs) being the most common. There was a higher risk of elevated CRP (>3 mg/L) in users of tricyclic antidepressant (TCA) medication (multivariate adjusted odds ratio (OR)=1.52, 95% CI, 1.07-2.15), but not in SSRI users (multivariate adjusted OR=1.07, 95% CI, 0.81-1.42). A longitudinal association between any antidepressant use and subsequent CRP was confirmed in the Whitehall cohort. In summary, the use of anti-depressants was associated with elevated levels of systemic inflammation independently from the symptoms of mental illness and cardiovascular co-morbidity. This might be a potential mechanism through which antidepressant medication increases CVD risk. Further data are required to explore the effects of dosage and duration of antidepressant treatment., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To investigate the association of polymorphisms in complement factor H (CFH) and coronary heart disease (CHD) using meta-analysis., Background: Age-related macular degeneration (AMD) and CHD may share partially overlapping pathogenesis. A non-synonymous SNP (rs1061170/Y402H) in CFH encoding complement factor H (fH) is robustly associated with increased AMD risk but associations with CHD risk have been inconsistent., Methods: We conducted de novo genotyping and genetic association analyses of incident and prevalent CHD in four studies, and in silico analysis of the same association in a further four cohorts. We pooled these data with information from all published studies using random effects meta-analysis, including a total of 48,646 participants of which 9097 were CHD cases. We also evaluated the association of Y402H with known risk factors for CHD by pooling results from new and in silico studies providing relevant data., Results: CFH genotype was not associated with CHD. Compared to the reference TT homozygote group the pooled odds ratio (OR) for individuals homozygous for the C allele was 1.02, 95% CI (0.91, 1.13) and that for heterozygote TC individuals was 1.04 (0.98, 1.10). There was no association of CFH with systolic and diastolic blood pressure, total-, LDL- and HDL-cholesterol, or body mass index. Individuals who were CC compared to TT had higher triglyceride levels: pooled mean difference 0.06 (0.02, 0.10) mmol/L, p=0.005., Conclusions: The AMD-associated CFH genotype is not associated with CHD. With the possible exception of triglycerides, this CFH SNP was not associated with a wide range of other CHD risk factors., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To examine the association of leisure time physical activity, walking pace and resting heart rate with disease-specific mortality in a prospective cohort study by reporting updated analyses of an earlier report we produced with the British epidemiologist, Jerry N. Morris (1910-2009)., Methods: In the original Whitehall study, 19,019 male, nonindustrial, London-based government employees, aged from 40 to 69 years in 1967 and 1970, participated in a medical examination during which data on leisure time physical activity (N = 6715), self-rated walking pace (N = 6729), and resting heart rate (N = 1183) were collected. Cox proportional hazards analyses were used to estimate hazard ratios for the relation between these exposures and disease-specific mortality., Results: In models adjusted for a range of covariates including socioeconomic status, smoking, and obesity, high resting heart rate was associated with a modestly elevated rate of mortality from all causes (hazard ratio; 95% confidence interval: tertile 3 vs. tertile 1: 1.17; 0.99, 1.37 p[trend]: 0.07) and respiratory disease (1.69; 1.04, 2.76 p[trend]: 0.03). Of the two markers of physical activity, walking pace was inversely related to mortality ascribed to all causes (slow vs. high walking pace 1.71; 1.53, 1.91 p[trend]: <0.001]), coronary heart disease (2.03; 1.68, 2.47 p[trend]: <0.001), and total cancers (1.25; 0.98, 1.59 p[trend]: 0.04). The corresponding associations for leisure time activity were typically weaker. For other mortality endpoints-respiratory disease (walking pace: 1.96; 1.48, 2.60 p[trend]: <0.001]), hematopoietic cancer (walking pace: 1.36; 0.52, 3.51 p[trend]: 0.03), stomach cancer (inactive versus active leisure time: 1.53; 0.88, 2.64 p[trend]: 0.04), and rectal cancer (walking pace: 4.85; 1.70, 13.8 p[trend]: 0.007)-individual activity indices revealed effects, but not both., Conclusions: Higher levels of physical activity indexed by the various markers herein appeared to confer protection against a range of mortality outcomes., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objectives: The association between depression and sub-clinical atherosclerosis remains unclear. By assessing depressive symptoms only at one point in time, most previous studies have failed to ascertain long-term exposure. We examined the association of long-term depressive symptoms assessed at three time points (over 10 yrs) with a marker of sub-clinical atherosclerosis., Methods: Participants included 454 healthy, non-medicated men and women from the Whitehall II epidemiological cohort without known cardiovascular disease (CVD). Depressive symptoms were assessed at three time points (over 10 yrs) and coronary atherosclerosis was assessed at follow-up in terms of coronary artery calcification (CAC)., Results: 18.9% of the sample reported depressive symptoms at least once during follow-up. Participants that were persistently depressed had over a two-fold increased risk of detectable CAC (Agatston score>0) (odds ratio [OR]=2.56, 95% CI, 1.14-5.78) and high CAC (Agatston score > or = 100) (OR=2.36, 1.04-5.35) compared with never depressed after adjustment for age, sex, and a range of conventional cardiac risk factors. These associations were more robust in men. Participants who were depressed on only one occasion were not at elevated risk of CAC., Conclusions: Persistent cognitive symptoms of depression assessed over several time points, but not on a single occasion, are related to sub-clinical coronary atherosclerosis in men free of known CVD and diabetes., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

The authors examined the association of 'g' (general intelligence) factor and five specific cognitive measures assessed in 1997-1999 with mortality till 2006 (mean follow-up of 8 years) in the middle-aged Whitehall II cohort study. In age- and sex-adjusted analysis, a decrease in 1 S.D. in memory (hazard ratio (HR), 1.19; 95% confidence interval (CI): 1.02, 1.39) and in Alice Heim 4-I (AH4-I) (HR, 1.16; 95% CI: 1.01, 1.35) was found to be associated with higher mortality. The association with 'g' factor, phonemic and semantic fluency did not reach significance at p<0.05. No association was found with vocabulary. Out of education, health behaviours and health measures, it was health behaviours that explained the greater part of the association between cognition and mortality, ranging from 21% for memory to 70% for semantic fluency. All the covariates taken together explained only 26% of the association with memory and between 33 and 90% for the other cognitive measures. This study suggests that 'g' type composite measure of cognition might not be enough to understand the associations between cognition and health., (Copyright (c) 2008 Elsevier Inc. All rights reserved.)

This study aims to examine social class differences in smoking, heavy drinking, unhealthy food habits, physical inactivity and obesity, and work-related psychosocial factors as explanations for these differences. This is done by comparing employee cohorts from Britain, Finland and Japan. Social class differences in health behaviours are found in the two western European countries, but not in Japan. The studied psychosocial factors related to work, work-family interface and social relationships did not explain the found class differences in health behaviours.

The purpose of this study was to investigate whether cognitive function in midlife predicts incident coronary heart disease (CHD), followed up over 6 years. Data on 5292 (28% women, mean age 55) individuals free from CHD at baseline were drawn from the British Whitehall II study. We used Cox regression to model the association between cognition and CHD in analyses adjusted for socio-demographic variables, cardiovascular risk factors and health behaviors. The results show a one standard deviation lower score on the "general" cognitive measure and measures of reasoning and vocabulary to be associated with elevated CHD risk. There was some evidence that these effects differed between high and low socioeconomic status (SES) groups with associations only seen in the low SES group. These results were not explained by threshold effects or by the different SES groups representing different parts of the cognitive test score distribution. Three other possible explanations of these results are discussed: sub clinical vascular disease drives the observed association but no effect is observed in the high SES group due to compensation provided by greater cognitive reserve, cognition is a marker of overall bodily integrity particularly in low-SES groups, and SES is a moderator of the association between cognition and CHD, because it marks a range of other risk factors.

Objective: To examine the impact of -174G>C and -572G>C variants in the promoter region of the IL6 gene, and their interactions with social position, on interleukin-6 (IL-6) levels in the Whitehall II cohort., Methods and Results: SNPs were genotyped by TaqMan. IL-6 was measured by ELISA. Employment grade was assessed to indicate social position. ANOVAs were used to examine genotype-phenotype associations. 4165 white men and women provided data on IL-6 levels at two study time points, Phase 3 (1991-1993) and Phase 7 (2002-2004). Distributions were as expected for Hardy-Weinberg equilibrium. At Phase 3, overall IL-6 levels did not differ by either genotype, but -174C was associated with higher IL-6 levels within the lowest employment grades (p(interaction)=0.046). At Phase 7, IL-6 levels overall were 6% higher in -174C (p=0.002) and 9% lower in -572C (p=0.003) carriers. The lowering effect of -572C was not apparent in the lowest employment grades (p(interaction)=0.05)., Conclusions: IL-6 levels are determined in part by interaction between common functional IL6 gene variants and yet to be identified components of social position. These results highlight the importance of considering interactions between genes and social environments in future study designs.

Background: The extent to which cognition in late midlife is influenced by lifetime obesity is unclear., Objective: We examined the association between body mass index (BMI) over the adult life course and cognition in late midlife and assessed the cumulative effects of obesity and underweight., Design: Data from the Whitehall II Study were examined. BMI at 25 y (early adulthood) was self-reported at phase 1 and was measured in early midlife (mean age = 44 y; phase 1) and in late midlife (mean age = 61 y; phase 7). Cognition (n = 5131) was assessed in late midlife (phase 7) by using the Mini-Mental State Examination and tests of memory and executive function, all of which were standardized to T scores (mean +/- SD: 50 +/- 10)., Results: Both underweight and obesity were associated with lower cognition in late midlife and with early adulthood, early midlife, and late midlife measures of BMI. Being obese at 2 or 3 occasions was associated with lower Mini-Mental State Examination scores and scores of memory and executive function in analyses adjusted for age, sex, and education [difference (95% CI) in mean T scores compared with normal-weight group: -1.51 (-2.77, -0.25), -1.27 (-2.46, -0.07), and -1.35 (-2.45, -0.24), respectively]. Participants who were underweight at > or =2 occasions from early adulthood to late midlife had lower executive function [difference (95% CI) in mean T score: -4.57 (-6.94, -2.20)]. A large increase in BMI from early to late midlife was associated with lower executive function., Conclusions: Long-term obesity and long-term underweight in adulthood are associated with lower cognitive scores in late midlife. Public health messages should promote a healthy weight at all ages.