Analysis of Circulating Cholesterol Levels as a Mediator of an Association Between ABO Blood Group and Coronary Heart Disease

BACKGROUND: Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non-O-type individuals. In this study, we sought to estimate the mediation effect size. METHODS AND RESULTS: In a group of individuals (n=6476) undergoing coronary angiography, we detected associations of non-O type with significant coronary artery disease with >50% stenosis in ≥1 coronary arteries (odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P=2.6×10(-4)) and with prevalent or incident myocardial infarction (odds ratio, 1.22; 95% confidence interval, 1.09-1.37; P=1.2×10(-3)). Subjects of non-O type had higher levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (mean [SEM] in mmol/L: 4.931[0.021], 3.041 [0.018], and 3.805 [0.020] in non-O type compared with 4.778 [0.026], 2.906 [0.021], and 3.669 [0.024] in O type; P=3.8×10(-7), P=1.5×10(-7), and P=3.1×10(-7), respectively). Mediation analyses indicated that 10% of the effect of non-O type on coronary artery disease susceptibility was mediated by increased low-density lipoprotein cholesterol level (P=7.8×10(-4)) and that 11% of the effect of non-O type on myocardial infarction risk was mediated by raised low-density lipoprotein cholesterol level (P=2.0×10(-3)). CONCLUSIONS: In a model in which it is presumed that cholesterol is a mediator of the associations of ABO group with coronary artery disease and myocardial infarction, around 10% of the effect of non-O type on coronary artery disease and myocardial infarction susceptibility was mediated by its influence on low-density lipoprotein cholesterol level.