The Association of Lipoprotein(a) and Circulating Monocyte Subsets with Severe Coronary Atherosclerosis

Abstract

Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) (Lp(a)) is a proven cardiovascular risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subpopulations in patients with a different severity of coronary atherosclerosis.

Methods: 150 patients (124 males) with a median age of 60 years undergoing a coronary angiography were enrolled. Lipids, Lp(a), autoantibodies, blood cell counts and monocyte subpopulations (classical, intermediate, non-classical) were analyzed.

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 by risk factors, autoantibody levels and blood cell counts. In patients with hyperlipoproteinemia(a) the content (absolute and relative) of non-classical monocytes was higher (71.0 (56.6; 105.7) vs. 62.2 (45.7; 82.4) 10³/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 monocytes with the Lp(a) concentration retained a statistical significance when adjusted for gender and age (r = 0.18, p = 0.03). The severity of coronary atherosclerosis was associated with the Lp(a) concentration as well as the relative and absolute (p < 0.05) content of classical monocytes. The high content of non-classical monocytes (OR = 3.5, 95% CI 1.2-10.8) as well as intermediate monocytes (OR = 8.7, 2.5-30.6) in patients with hyperlipoproteinemia(a) were associated with triple-vessel coronary disease compared with patients with a normal Lp(a) level and a low content of monocytes.

Conclusion: Hyperlipoproteinemia(a) and a decreased quantity of classical monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperlipoproteinemia(a) significantly increased the risk of triple-vessel coronary disease.

Keywords: atherosclerosis; autoantibodies; coronary artery disease; hyperlipoproteinemia(a); inflammation; intermediate CD14++CD16+ monocyte; lipoprotein(a); monocyte subset; multivessel coronary disease; non-classical CD14+CD16++ monocyte.

Figure 1

Absolute (A,C,E) and relative (B,D,F) content of the monocyte subsets in the groups of patients with (“1”) and without (“0”) hyperlipoproteinemia(a). Data are presented as a median and a 95% confidential interval for the median. Mn = monocyte content. “ns”—not significant (p > 0.05).

Figure 2

Percentage of patients with triple-vessel coronary disease (CAD) in accordance with Lp(a) quartiles, mg/dL: Q1 < 7.2, Q2 from 7.2 to 24.3; Q3 from 24.4 to 67.8; Q4 ≥ 67.8.

Figure 3

Coronary atherosclerosis and the percentage of the monocyte subsets. Data are presented as absolute numbers and the percentage of patients with a varying severity of coronary artery disease depending on the relative of the monocyte subset below and above the median. The median value for classic CD14++CD16− monocytes was 73.6%, intermediate CD14++CD16+ was 7.3% and non-classical CD14+CD16++ was 16.4%. (A)—classical CD14++CD16−, (B)—intermediate CD14++CD16+ and (C)—non-classical CD14+CD16++ monocytes. Me = median.

Figure 4

Severity of coronary artery disease depending on the presence of hyperLp(a) and the relative content of classical CD14++CD16− (A), intermediate CD14++CD16+ (B) and non-classical CD14+CD16++ monocytes (C). The data are presented as the percentage of patients and the absolute number of patients (numbers within the bars) with a different severity of coronary atherosclerosis in the subgroups depending on the combination of normal (<30 mg/dL) and increased (≥30 mg/dL) concentrations of Lp(a) as well as the relative content of monocytes below and above the median. The corresponding values of the median for the relative (% of the total number of monocytes) content of classical CD14++CD16−, intermediate CD14++CD16+ and non-classical CD14+CD16++ subpopulations of monocytes correspond to the values indicated in Table 3. Me = median.