Lipoprotein(a), Immunity, and Inflammation in Polyvascular Atherosclerotic Disease

Abstract

Background and aims: lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and its complications, although data on the association with other vascular beds and the severity of atherosclerosis is limited. The aim of this study was to evaluate the association of atherosclerosis of various vascular beds with Lp(a), as well as its autoantibodies and generalized inflammatory markers.

Material and methods: this study included 1288 adult patients with clinical and imaging examination of three vascular beds (coronary, carotid, and lower limb arteries). Patients were categorized according to the number of affected vascular beds (with at least one atherosclerotic stenosis ≥50%): 0 (n = 339), 1 (n = 470), 2 (n = 315), 3 (n = 164). We assessed blood cell count, lipid profile, C-reactive protein, circulating immune complexes, Lp(a), and its autoantibodies.

Results: the number of affected vascular beds was associated with an increasing level of Lp(a) and a lower level of IgM autoantibodies to Lp(a). Hyperlipoproteinemia(a) (Lp(a) ≥ 30 mg/dL) was detected more frequently in patients with atherosclerosis. In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, and smoking, an elevated Lp(a) level was independently associated with stenotic atherosclerosis and lesion severity. There was a positive association of the number of affected vascular beds with C-reactive protein (r = 0.21, p < 0.01) and a negative association with circulating immune complexes (r = -0.29, p < 0.01). The neutrophil-to-lymphocyte ratio was significantly higher and the lymphocyte-to-monocyte ratio was significantly lower in patients with atherosclerosis compared to the controls (p < 0.01).

Conclusion: Lp(a), C-reactive protein, circulating immune complexes, and neutrophil-to-lymphocyte ratio are associated with the stenotic atherosclerosis of different vascular beds. Lp(a) levels increase and IgM autoantibodies to Lp(a) decrease with the number of affected vascular beds.

Keywords: C-reactive protein; apolipoprotein(a); atherosclerosis; atherosclerosis of lower limb arteries; autoantibodies; carotid artery disease; circulating immune complexes; coronary artery disease; hyperlipoproteinemia(a); lipoprotein(a).

Figure 1

(A) The levels of lipoprotein(a). (B) IgM autoantibodies to lipoprotein(a) (the levels of specific autoantibodies against Lp(a) and LDL were determined in the serum of 512 randomly selected representative patients: group 0, n = 72; group I, n = 153; group II, n = 183; group III, n = 104). (C) Circulating immune complexes. (D) C-reactive protein, depending on the number of affected vascular beds. Data are presented as the median and 95% confidence interval. Lp(a): lipoprotein(a), CICs: circulating immune complexes, CRP: C-reactive protein, autoAb: autoantibody.

Figure 2

The distribution of elevated level of lipoprotein(a) (A) depending on the number of affected vascular beds, (B) in patients with different cardiovascular diseases. CAD: coronary artery disease, CVD: cerebrovascular disease, LEAD: lower extremity artery disease.

Figure 3

Odds ratios of cardiovascular diseases (A) in the case of hyperlipoproteinemia(a), and (B) in the case of hyperlipoproteinemia(a) and the level of IgM autoantibodies against lipoprotein(a) being below the median. Data are presented as odds ratio (ORs) and 95% confidence intervals. CAD: coronary artery disease, CVD: cerebrovascular disease, LEAD: lower extremity artery disease.