Circulating lipoprotein subfractions as new non-invasive biomarkers of coronary atherosclerosis

Objectives Coronary artery disease (CAD) is the most common cause of death globally. In the next decade, the number of people at risk is expected to increase, due to obesity, inactivity and diabetes. Therefore, precise risk-prediction models will be increasingly important for the healthcare system, to be able to initiate cost-efficient prevention strategies. One of the first steps in CAD-development is sub-clinical atherosclerosis. Biomarkers that could reflect the presence of coronary atherosclerosis would be extremely valuable for risk prediction of myocardial infarction (MI). Serum cholesterol levels are key variables in risk prediction; however, there is growing interest for exploring the potential of other lipid subclasses. The aim of this study is to identify specific lipoprotein subfractions that are associated with the extent of coronary atherosclerosis. Methods 60 patients with suspected CAD were enrolled. Blood samples were collected before the partiens underwent coronary angiography. The extent of coronary atherosclerosis were quantified using the Gensini score. The partients were classified into three groups based on their Gensini score (30.1: significant CAD). The blood samples were analyzed by nucelar magnetic resonance (NMR) lipidomics. Univariate and multivariate statistical tests were used to determine whether lipoprotein subfractions were associated with the extent of coronary atherosclerosis. Results and discussion Of the 117 lipoprotein subfractions quantified, 10 were different in patients with significant CAD compared to patients with normal vessels in non-statin users (p=0.005). Despite no difference in total cholesterol, LDL and HDL cholesterol between the three Gensini groups, NMR lipidomics revealed that patients with significant CAD had twice as many circulating LDL-5 and LDL-6 particles as patients with normal vessels. Furthermore, three types of small LDL-subfractions, called LDL-5-TG, LDL-5-ApoB and LDL-6-ApoB, were significantly increased in patients with significant CAD. Interestingly, previous studies have suggested that small LDL particles are more atherogenic than larger particles. In addition, patients with significant CAD had low levels of ApoA1 containing HDL particles, and high levels of two different small VLDL particles. Previous studies have indicated that small VLDLs are more atherogenic than larger VLDLs, and does to a greater extent penetrate the vessel intima. Conclusions This study reveals strong associations between serum lipoprotein subfractions and the degree of coronary atherosclerosis quantified by Gensini score. Especially, the high levels of certain types of small LDL-particles in patients with CAD, indicates that measuring lipoprotein subfractions may provide added value to risk prediction models for MI. However, these findings needs to be further explored and validated in large cohort studies.