Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study

Objectives
To investigate the role of body mass index, systolic blood pressure and smoking in explaining the effect of education on risk of cardiovascular disease outcomes.

Design
Multivariable regression analysis of observational data and Mendelian randomisation (MR) analysis of genetic data.

Setting
UK Biobank and international genome-wide association study data.

Participants
Predominantly individuals of European ancestry.

Exposure
Educational attainment, body mass index, systolic blood pressure and smoking in observational analysis, and randomly allocated genetic variants to instrument these traits in Mendelian randomisation.

Main outcomes measure
Risk of coronary heart disease, cardiovascular disease (all subtypes), myocardial infarction and stroke (all measured in odds ratio, OR), and the degree to which this is mediated through body mass index, systolic blood pressure and smoking respectively.

Results
Each additional standard deviation of education (3.6 years) associated with 13% lower risk of coronary heart disease (OR 0.86, 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 randomisation analysis. As a proportion of the total risk reduction, body mass index was estimated to mediate 15% (95% CI 13% to 17%) and 18% (95% CI 14% to 23%) in the observational and Mendelian randomisation 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 34% (95% CI 17% to 50%). All three risk factors combined were estimated to mediate 42% (95% CI 36% to 48%) and 36% (95 % CI 5% to 68%) of the effect of education on coronary heart disease in observational and Mendelian randomisation respectively. Similar results were obtained when investigating risk of stroke, myocardial infarction and all-cause cardiovascular disease.

Conclusions
Body mass index, systolic blood pressure 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.