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

• Published in: BMJ (Online) 2019-05, Vol.365, p.l1855-l1855
• Main 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, Davey Smith, George, Holmes, Michael V, Tzoulaki, Ioanna, Howe, Laura D, Dehghan, Abbas
• Format: Article
• Language: English
• Subjects: Adult; Aged; Blood Pressure; Body Mass Index; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cerebral infarction; Coronary artery disease; Educational Status; Female; Genetic analysis; Genetic diversity; Genome-wide association studies; Genomes; Health risk assessment; Heart diseases; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Multivariate Analysis; Myocardial infarction; Odds Ratio; Risk Factors; Smoking; Smoking - adverse effects; Socioeconomic Factors; United Kingdom
• ISSN: 0959-8138; 1756-1833
• DOI: 10.1136/bmj.l1855

AbstractObjectivesTo 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.DesignMendelian randomisation study.SettingUK Biobank and international genome-wide association study data.ParticipantsPredominantly participants of European ancestry.ExposureEducational 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 measureThe 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.ResultsEach 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.ConclusionsBMI, 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.