What explains the effect of education on cardiovascular disease? Applying Mendelian randomization to identify the consequences of education inequality
Authors: Carter Alice R , Gill Dipender , Davies Neil M , Taylor Amy E , Tillmann Taavi , Vaucher Julien , Wootton Robyn E , Munafò Marcus R , Hemani Gibran , Malik Rainer , Seshadri Sudha , Woo Daniel , Burgess Stephen , Smith George Davey , Holmes Michael V , Tzoulaki Ioanna , Howe Laura D , Dehghan Abbas 
Published: December 2018

Key PointsQuestionWhat is the role of body mass index, systolic blood pressure and smoking in mediating the effect of education on cardiovascular disease risk?FindingWe find consistent evidence that body mass index, systolic blood pressure and smoking mediate the effect of education, explaining up to 18%, 27% and 33% respectively. Including all three risk factors in a model together explains around 40% of the effect of education.MeaningIntervening on body mass index, systolic blood pressure and smoking would lead to reductions in cases of CVD attributable to lower levels of education. Over half of the effect of education on risk of cardiovascular disease is not mediated through these risk factors.ImportanceLower levels of education are causally related to higher cardiovascular risk, but the extent to which this is driven by modifiable risk factors also associated with education is unknown.ObjectiveTo investigate the role of body mass index, systolic blood pressure and smoking in explaining the effect of education on risk of cardiovascular disease outcomes.DesignMultivariable regression analysis of observational data and Mendelian randomization (MR) analysis of genetic data.SettingUK Biobank and international genome-wide association study consortia.ParticipantsPredominantly individuals of European ancestry.Main outcomes and measuresThe effects of education (per 1-standard deviation increase, equivalent to 3.6 years) on coronary heart disease, cardiovascular disease (all subtypes), myocardial infarction and stroke risk (all measured in odds ratio, OR), and the degree to which this is mediated through body mass index, systolic blood pressure and smoking.ResultsEach additional standard deviation of education associated with 13% lower risk of coronary heart disease (OR 0.87, 95% confidence interval [CI] 0.84 to 0.89) in observational analysis and 37% lower risk (OR 0.63, 95% CI 0.60 to 0.67) in Mendelian randomization analysis. As a proportion of the total risk reduction, body mass index mediated 15% (95% CI 13% to 17%) and 18% (95% CI 14% to 23%) in the observational and Mendelian randomization estimates, respectively. Corresponding estimates for systolic blood pressure were 11% (95% CI 9% to 13%) and 21% (95% CI 15% to 27%), and for smoking, 19% (15% to 22%) and 33% (95% CI 17% to 49%). All three risk factors combined mediated 42% (95% CI 36% to 48%) and 36% (95 % CI 16% to 63%) of the effect of education on coronary heart disease in observational and Mendelian randomization respectively. Similar results were obtained when investigating risk of stroke, myocardial infarction and all-cause cardiovascular disease.Conclusions and relevanceBMI, SBP and smoking mediate a substantial proportion of the protective effect of education on risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of CVD attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.