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 predisposition to coronary heart disease. It is believed 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 (CAD) with >50% stenosis in one or more coronary arteries (OR=1.24, 95%CI=1.10-1.39, p=2.6×10-4) and with prevalent or incident myocardial infarction (MI) (OR=1.22, 95%CI=1.09-1.37, p=1.2×10-3). Subjects of non-O type had higher levels of total cholesterol (TC), low-density-lipoprotein-cholesterol (LDLc) and non-low-density-lipoprotein-cholesterol (NHDLc) (mean (S.E.M.) 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, 1.5×10-7 and 3.1×10-7, respectively). Mediation analyses indicated that 10% of the effect of non-O type on CAD susceptibility was mediated by increased LDLc level (p=7.8×10-4) and that 11% of the effect of non-O type on MI risk was mediated by raised LDLc 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 CAD and MI, around 10% of the effect of non-O type on CAD and MI susceptibility was mediated by its influence on LDLc level.
- ABO blood group
- low-density lipoprotein cholesterol
- coronary heart disease
- myocardial infarction
- Received July 24, 2013.
- Revision received December 3, 2013.
- Accepted December 18, 2013.