What explains the effect of education on cardiovascular disease? Applying Mendelian randomization to identify the consequences of education inequality

Abstract

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.

Education protects against coronary heart disease and stroke independently of cognitive function: evidence from Mendelian randomization

“…The protective role of educational attainment on cardiovascular disease (CVD) has been described in previous observational work, 5 , 36 , 37 as well as recent MR studies, 8 , 9 but adjustment for cognitive function was not performed in these particular analyses and neither did they focus on the distinction between educational attainment and cognitive function in relation to cardiovascular risk. However, a recent study has used MVMR to suggest that the protective effect of education on likelihood of smoking was not due to an effect of cognitive function, 14 and as smoking is an established risk factor for cardiovascular disease, this is consistent with our current work.…”

“…Randomized controlled trials (RCTs), on the other hand, are not a plausible option for studying the effects of cognition or education 7 . Whereas previous work has investigated the effect of educational attainment on cardiovascular disease risk 8 , 9 further disentangling the independent effects of education and cognition would have important implications for public health and educational policy, particularly with regard to allocation of resources towards targeting the relevant exposure. For example, in the scenario where education is causally related to developing CHD or stroke independently of cognitive function, but not vice versa, strategies for increasing education rather than cognitive ability would better protect against adverse health outcomes.…”

Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour

“…show that smoking mediates the observed effect of education on cardiovascular disease. 5 It is therefore plausible that some of the effect of educational attainment on risk of CHD (and other adverse health outcomes) is mediated via effects on smoking behaviour.…”

Causal effects of serum levels of n-3 or n-6 polyunsaturated fatty acids on coronary artery disease: Mendelian randomization study

“…MR has been implemented in the medical literature and has identified important causal factors for the risk of CAD or other chronic comorbidities. [15][16][17][18] In this study, we aimed to investigate the causal effects of serum n-3 and n-6 PUFA levels on the risk of CAD by MR analysis testing the association between genetic predisposition for each PUFA type and the risk of CAD or myocardial infarction (MI). We performed both allele-score-based MR by individual-level data and MR based on summary-level data in different cohorts to replicate the findings.…”