Association of elevated lipoprotein(a) level and monocyte subsets with the severity of coronary atherosclerosis

Abstract

Abstract Background Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role at all stages of atherogenesis. Monocytes are a heterogeneous population, and each subset contributes differently to the inflammatory process. High level of lipoprotein(a) [Lp(a)] is a proven atherosclerotic cardiovascular disease (ASCVD) risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subsets in patients with different severity of coronary atherosclerosis. Methods 150 patients (124 males (82.6%)), median age 60 (54; 65) years undergoing coronary angiography were enrolled. Lipids, Lp(a) were assessed by enzyme immunoassay. Monocyte subpopulations (classical CD14++CD16-, intermediate CD14++CD16+, non-classical CD14+CD16++) were analyzed by direct immunofluorescence and flow cytometry. Results The patients were divided into two groups depending on the Lp(a) concentration: normal Lp(a) <30 mg/dl (n=82) and hyperLp(a) ≥30 mg/dl (n=68). Patients of both groups were comparable in routine ASCVD risk factors (age, BMI, arterial hypertension, previous myocardial infarction, smoking, lipids). In patients with hyperLp(a) the content (absolute and relative) of non-classical CD14+CD16++ monocytes was higher (71.0 (56.6; 105.7 1000/ml vs. 62.2 (45.7; 82.4) 1000/ml and 17.7 (13.0; 23.3) % vs. 15.1 (11.4; 19.4) %, respectively, p<0.05). The association of the relative content of non-classical CD14+CD16++ monocytes with the Lp(a) concentration retained statistical significance when adjusted for gender and age (r=0.18, p=0.03). The severity of coronary atherosclerosis was correlated with the Lp(a) concentration (r=0.20, p<0.05), as well as the relative (r=−0.16, p<0.05) and absolute (r=−0.21, p<0.05) content of classical CD14++CD16- monocytes. The high content of non-classical CD14+CD16++ monocytes (OR=3.5 (95% CI 1.2–10.8), as well as intermediate CD14++CD16+ monocytes (OR=8.7 (95% CI 2.5–30.6) in patients with hyperLp(a) were associated with stenotic three-vessel coronary artery disease. Conclusion Here we demonstrate the correlation between the Lp(a) concentration and the blood content of non-classical monocytes, regardless of gender and age. The hyperLp(a) and decreased quantity of classical CD14++CD16- monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperLp(a) significantly increased the risk of stenotic three-vessel coronary artery disease. Further studies of the differentiation and functioning of subsets of monocytes in the presence of congenital disorders of lipid metabolism, and especially hyperLp(a), are needed. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The study was approved by Russian Ministry of Health