Lipoprotein(a) and Its Autoantibodies in Association with Calcific Aortic Valve Stenosis.

Aortic valve stenosis is the most common valvular heart disease in the Western world. Lipoprotein(a) (Lp(a)) is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). The aim of this study was to assess the role of Lp(a) and its autoantibodies [autoAbs] in CAVS in patients with and without CHD. We included 250 patients (mean age 69 ± 3 years, males 42%) and divided them into three groups. There were two groups of patients with CAVS depending on the presence (group 1) or absence of CHD (group 2). The control group included the patients without CHD or CAVS. According to logistic regression analysis, levels of Lp(a), IgM autoAbs to oxidized Lp(a) (oxLp(a)), and age were independent predictors of CAVS. A concomitant increase in Lp(a) level (≥30 mg/dL) and a decrease in IgM autoAbs concentration (<9.9 lab. Units) are associated with CAVS with an odds ratio (OR) of 6.4, p < 0.01, and with CAVS and CHD with an OR of 17.3, p < 0.001. IgM autoantibodies to oxLp(a) are associated with calcific aortic valve stenosis regardless of Lp(a) concentration and other risk factors. Higher Lp(a) and lower IgM autoantibodies to oxLp(a) levels are associated with a much higher risk of calcific aortic valve stenosis.

The Concentration of PCSK9-Lp(a) Complexes and the Level of Blood Monocytes in Males with Coronary Atherosclerosis.

In this study we analyzed the concentration of lipoprotein(a) (Lp(a)), PCSK9-Lp(a) complexes and the circulating monocyte subsets in coronary atherosclerosis. For this study, 257 patients with coronary atherosclerosis and 68 patients without stenotic atherosclerosis in the coronary, carotid and lower extremity arteries (control group) were enrolled. The monocyte subpopulations (classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++) were analyzed by direct immunofluorescence and flow cytometry. The Lp(a) and PCSK9-Lp(a) complexes in the serum were detected by ELISA. The concentration of Lp(a) was higher in the coronary atherosclerosis group compared with the controls (23.0 (9.1; 73.3) mg/dL versus 10.7 (4.7; 25.0) mg/dL, p < 0.05). No correlations between the level of Lp(a) and the concentration of the PCSK9-Lp(a) complexes, nor between the level of Lp(a) or PCSK9 and the total number of monocytes, were observed in either group. A slight positive correlation between the concentration of PCSK9-Lp(a) complexes and the absolute level of monocytes was obtained (r = 0.20, p = 0.002) in the patients with atherosclerosis due to the intermediate monocyte subsets (r = 0.33, p = 0.04). According to regression analysis, both the PCSK9-Lp(a) complexes concentration and BMI were related to the absolute number of blood monocytes in patients with atherosclerosis. Further studies are required to determine the pathogenetic contribution of PCSK9-Lp(a) complexes to the development of atherosclerosis.

Hyperlipoproteinemia(a) and Severe Coronary Artery Lesion Types.

Diffuse atherosclerosis and calcification of the coronary arteries (CA) create serious difficulties for coronary artery bypass grafting (CABG). The aim of this study was to compare demographic indicators, lipids, and clinical results one year after CABG in patients with different phenotypes of coronary artery (CA) disease. In total, 390 patients hospitalized for elective CABG were included in a single-center prospective study. Demographic data, lipids (total, low-density lipoprotein and high-density lipoprotein cholesterol, and triglycerides), and lipoprotein(a) (Lp(a)) concentrations were analyzed for all patients. Major adverse cardiovascular events (MACE) included myocardial infarction, stroke, percutaneous coronary intervention, and death from cardiac causes within one year after surgery. No significant outcome differences were found between the groups with diffuse vs. segmental lesions, nor the groups with and without calcinosis for all studied parameters except for Lp(a). Median Lp(a) concentrations were higher in the group of patients with diffuse compared to segmental lesions (28 vs. 16 mg/dL, p = 0.023) and in the group with calcinosis compared to the group without it (35 vs. 19 mg/dL, p = 0.046). Lp(a) ≥ 30 mg/dL was associated with the presence of diffuse lesions (OR = 2.18 (95% CI 1.34-3.54), p = 0.002), calcinosis (2.15 (1.15-4.02), p = 0.02), and its combination (4.30 (1.81-10.19), p = 0.0009), irrespective of other risk factors. The risk of MACE within one year after CABG was higher for patients with combined diffuse and calcified lesions vs. patients with a segmental lesion without calcinosis (relative risk = 2.38 (1.13-5.01), p = 0.02). Conclusion: Diffuse atherosclerosis and coronary calcinosis are associated with elevated Lp(a) levels, independent of other risk factors. The risk of MACE in the first year after surgery is significantly higher in patients with diffuse atherosclerosis and coronary calcinosis, which should be considered when prescribing postoperative treatment for such patients.

Ig apheresis for the treatment of severe DCM patients.

BACKGROUND: Autoantibodies against ß1-adrenoreceptor (AR) are considered by many authors to be the most significant in autoimmune process during DCM. Immunoadsorption (IA) of immunoglobulins (Ig apheresis) is a logic approach to remove autoantibodies against ß1-AR and other antibodies. The effect of Ig apheresis and the role of anti-ß1-AR in DCM are still an issue for discussion. METHODS: We have performed a prospective case-control study in 16 patients with DCM, NYHA Class II-IV congestive heart failure, positive and negative for anti-ß1-AR. RESULTS: We observed a clinically significant mean change of exercise tolerance compared with controls (6 MWT distance increased from 420 ± 130 m to 550 ± 150 m, p < 0.05). Systolic function improved rapidly by increase in LVEF from 28.6 ± 5.2% to 33.0 ± 10.3%, LV end-systolic and end-diastolic volumes decreased from 166 ± 58 mL to 148 ± 50 mL and from 235 ± 73 mL to 220 ± 73 mL, respectively, whereas in the control group there was no significant change in clinical variables. The improved quality of life and cardiac function in apheresis group as well as negative changes in control group didn't correlate with the presence of anti-ß1-AR. CONCLUSIONS: Ig apheresis for the treatment of DCM patients is associated with the improvement of quality of life and cardiac function regardless of the presence of anti-ß1-AR. We suggest that IgG apheresis is a safe and effective method for DCM patients.