Taavi Tillmann

OBJECTIVES: To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. DESIGN: Mendelian randomisation study. SETTING: UK Biobank and international genome-wide association study data. PARTICIPANTS: Predominantly participants of European ancestry. EXPOSURE: Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. MAIN OUTCOMES MEASURE: The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. RESULTS: Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. CONCLUSIONS: BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.

<b>Objective</b>&nbsp;To determine whether educational attainment is a causal risk factor in the development of coronary heart disease. <b>Design</b>&nbsp;Mendelian randomisation study, using genetic data as proxies for education to minimise confounding. <b>Setting</b>&nbsp;The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors. <b>Participants</b>&nbsp;The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin. <b>Exposure</b>&nbsp;A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education. <b>Main outcome measure</b>&nbsp;Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D). <b>Results</b>&nbsp;Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10⁻⁸). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile. <b>Conclusions</b>&nbsp;This mendelian randomisation study found support for the hypothesis that low education is a causal risk factor in the development of coronary heart disease. Potential mechanisms could include smoking, body mass index, and blood lipids. In conjunction with the results from studies with other designs, these findings suggest that increasing education may result in substantial health benefits.

BACKGROUND: The social determinants of health have been widely recognised yet there remains a lack of clarity regarding what constitute the macro-economic determinants of health and what can be done to address them. An umbrella review of systematic reviews was conducted to identify the evidence for the health and health inequalities impact of population level macroeconomic factors, strategies, policies and interventions. METHODS: Nine databases were searched for systematic reviews meeting the Database of Abstracts of Reviews of Effects (DARE) criteria using a novel conceptual framework. Studies were assessed for quality using a standardised instrument and a narrative overview of the findings is presented. RESULTS: The review found a large (n = 62) but low quality systematic review-level evidence base. The results indicated that action to promote employment and improve working conditions can help improve health and reduce gender-based health inequalities. Evidence suggests that market regulation of tobacco, alcohol and food is likely to be effective at improving health and reducing inequalities in health including strong taxation, or restriction of advertising and availability. Privatisation of utilities and alcohol sectors, income inequality, and economic crises are likely to increase health inequalities. Left of centre governments and welfare state generosity may have a positive health impact, but evidence on specific welfare interventions is mixed. Trade and trade policies were found to have a mixed effect. There were no systematic reviews of the health impact of monetary policy or of large economic institutions such as central banks and regulatory organisations. CONCLUSIONS: The results of this study provide a simple yet comprehensive framework to support policy-makers and practitioners in addressing the macroeconomic determinants of health. Further research is needed in low and middle income countries and further reviews are needed to summarise evidence in key gaps identified by this review. TRIAL REGISTRATION: Protocol for umbrella review prospectively registered with PROSPERO CRD42017068357.

BACKGROUND: Although tuberculosis (TB) incidence has been decreasing in the European Union/European Economic Area (EU/EEA) in the last decades, specific subgroups of the population, such as migrants, remain at high risk of TB. This study is based on the report 'Key Infectious Diseases in Migrant Populations in the EU/EEA' commissioned by The European Centre for Disease Prevention and Control. METHODS: We collected, critically appraised and summarized the available evidence on the TB burden in migrants in the EU/EEA. Data were collected through: (i) a comprehensive literature review; (ii) analysis of data from The European Surveillance System (TESSy) and (iii) evidence provided by TB experts during an infectious disease workshop in 2012. RESULTS: In 2010, of the 73,996 TB cases notified in the EU/EEA, 25% were of foreign origin. The overall decrease of TB cases observed in recent years has not been reflected in migrant populations. Foreign-born people with TB exhibit different socioeconomic and clinical characteristics than native sufferers. CONCLUSION: This is one of the first studies to use multiple data sources, including the largest available European database on infectious disease notifications, to assess the burden and provide a comprehensive description and analysis of specific TB features in migrants in the EU/EEA. Strengthened information about health determinants and factors for migrants' vulnerability is needed to plan, implement and evaluate targeted TB care and control interventions for migrants in the EU/EEA.

AIMS: Progress towards meeting the goal of measles elimination in the EU and the European Economic Area (EEA) by 2015 is being obstructed, as some children are either not immunized on time or never immunized. One group thought to be at increased risk of measles is migrants; however, the extent to which this is the case is poorly understood, due to a lack of data. This paper addresses this evidence gap by providing an overview of the burden of measles in migrant populations in the EU/EEA. METHODS: Data were collected through a comprehensive literature review, a country survey of EU/EEA member states and information from measles experts gathered at an infectious disease workshop. RESULTS: Our results showed incomplete data on measles in migrant populations, as national surveillance systems do not systematically record migration-specific information; however, evidence from the literature review and country survey suggested that some measles outbreaks in the EU/EEA were due to sub-optimal vaccination coverage in migrant populations. CONCLUSIONS: We conclude that it is essential that routine surveillance of measles cases and measles, mumps and rubella (MMR) vaccination coverage become strengthened, to capture migrant-specific data. These data can help to inform the provision of preventive services, which may need to reach out to vulnerable migrant populations that currently face barriers in accessing routine immunization and health services.