[The relationship between the level of Lр(а) and the prevalence of atherosclerosis among young patients].

BACKGROUND: Hyperlipoproteinemia (a) is an independent and cause risk factor for atherosclerotic cardiovascular diseases (ASCVD). The correlation between lipoprotein (a) Lp(a) and inflammation in the vessel wall was actively studied during the past few years. C-reactive protein (CRP) plays an important role in ASCVD. AIM: To analyze the relationship between hyperlipoproteinemia (a), inflammatory markers, and the early development of stenosing atherosclerosis (AS) in several vascular pools. MATERIALS AND METHODS: 76 patients, 55 men aged 18 to 55 years and 21women 18 to 60 years, with the results of instrumental examination of coronary, carotid and lower extremities vascular pools were enrolled. Three groups: with stenosing (50%) AS of only one (group 1, n=29); two or three (group 2, n=21) vascular pools. 26 patients without coronary heart disease and AS were included in the control group. All patients in groups 1 and 2 and 65% of those in the control group took statins. The concentrations of Lp(a), CRP, lipids and blood count were determined. RESULTS: The patients of the three groups did not differ in age. In the groups with AS (79% in group 1 and 85% in group 2), there were more men (relative to 54% in the control group). Diabetes mellitus was more common only in patients with multifocal AS. The absolute number of blood monocytes and leukocytes, the neutrophil-lymphocyte ratio, as well as Lp(a) level were higher in patients of groups 1 and 2 relative to the control. The maximum Lp(a) level (median [25%; 75%]) was observed in patients with lesions of two or more vascular pools vs the control group (49 [4; 96] mg/dL, vs 10 [4; 21] mg/dL, p=0.02). The CRP level was significant elevated in patients from group 2 7.2 [4.0; 9.7] mg/L, relative to group 1 2.5 [1.0; 4.7] mg/L, and the control group 2.9 [1.2; 4.9] mg/L, p0.05. The Lp(a) and CRP concentration, or the presence of diabetes mellitus in patients, regardless of other risk factors, were associated with severe stenosing AS in young and middle age. CONCLUSION: An elevated concentration of Lp(a) (30 mg/dL) determines the presence of both isolated and multifocal stenosing AS in the examined patients. A simultaneous increase in the concentration of both Lp(a) and CRP, as well as the presence of diabetes mellitus, are associated with the premature development of stenosing atherosclerotic lesions in several vascular regions at once. Measurement of these predictors in young and middle-aged patients makes it possible to use them as biochemical markers to assess the likelihood of multifocal lesions of the vascular pool.

[Association of lipoprotein (a) with ischemic stroke and stenotic carotid atherosclerosis]. / Sviaz' lipoproteida(a) s ishemicheskim insul'tom i stenoziruiushchim aterosklerozom sonnykh arterii.

INTRODUCTION: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor of coronary heart disease and its complications. Meanwhile data about the role of Lp(a) in development of ischemic stroke are controversial. AIM: To investigate the association of Lp(a) with atherothrombotic ischemic stroke and stenotic (≥50%) atherosclerosis of carotid arteries. MATERIAL AND METHODS: The study included 490 patients (mean age 60 years, 53% male). The first group comprised 157 patients with ischemic stroke, the second group 68 patients with isolated stenotic atherosclerosis of carotid arteries, but without significant lesion of coronary and low limbs arteries. The control group included 265 patients without stroke, myocardial infarction, stenotic atherosclerosis of coronary, carotid and low limbs arteries according to instrumental examinations. The levels of Lp(a) and lipids were measured in blood serum of all patients. RESULTS: Lp(a) concentration was significantly higher in patients of the first and second groups in comparison with the control group (median [interquartile range]): 24 [9; 48], 20 [8; 55] vs 13 [5; 27] mg/dl, respectively (p<0,05 in both cases). Hyperlipoproteinemia(a) (Lp(a) ≥30 mg/dl) was more frequent in the group with stroke, stenotic atherosclerosis of carotid arteries, than in the control group: 43%, 40% vs 22% (p<0.01 in all cases). In patients with hyperlipoproteinemia(a), odds ratio (OR) for ischemic stroke was 2.7 (95% confidence interval (CI) 1.7-4.1), and OR for stenotic atherosclerosis of carotid arteries was 2.3 (95% CI 1.3-4.0) compared to the patients with Lp(a) level <30 mg/dl (p<0.01 in both cases). In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, smoking and Lp(a) concentration, the hyperlipoproteinemia(a) was associated with ischemic stroke and isolated stenotic carotid atherosclerosis. In the group with severe carotid atherosclerosis, 16 patients (24%) had ischemic stroke. Lp(a) concentration in these patients was higher 36 [20; 59] mg/dl, than in the patients with isolated carotid atherosclerosis without stroke 15 [7; 54] mg/dl (p=0.04). Other risk factors of atherosclerosis did not differ in patients with or without ischemic stroke. CONCLUSION: The study shows the association of elevated level of Lp(a) with ischemic stroke and isolated stenotic atherosclerosis of carotid arteries. In the presence of isolated stenotic carotid atherosclerosis, the median of Lp(a) concentration was significantly higher in patients with ischemic stroke than in patients without stroke.

[Lipoprotein(а) Level, Apolipoprotein(а) Polymorphism аnd Autoаntibodies Against Lipoprotein(а) in Patients with Stenotic Cаrotid Atherosclerosis].

Аim. Comparative assessment of respiratory indicators according to multifunctional monitoring (PFM) with the recommended standard for a complete polysomnographic study and an assessment of the effect of blood pressure (BP) measurements in PFM on sleep quality. Triаls on the аssociаtion of Lp(а) and cаrotid аtherosclerosis аre limited. The аim of the study wаs to investigаte the аssociаtion of Lp(а), аpolipoprotein(а) [apo(а)] polymorphism аnd аutoаntibodies to Lp(а) with stenotic (≥50%) cаrotid аtherosclerosis in dependence on CHD presence. Materials and methods. The study included 785 pаtients аt the аge from 21 to 92 with dаtа of instrumentаl exаmination of coronаry, cаrotid аnd lower limbs аrteries. Stenotic cаrotid аtherosclerosis wаs diаgnosed in 447 pаtients who were divided into two groups depending on presence (n=344) or аbsence (n=103) of CHD. The control group comprised of 338 pаtients without stenotic аtherosclerosis of coronаry, cаrotid аnd lower limbs аrteries. In the blood serum of pаtients levels of Lp(а), аutoаntibodies to Lp(а) were determined аnd аlso аpo(а) phenotyping wаs conducted. Results. There were more mаles, higher аverаge аge аnd frequency of hypertension, type 2 diаbetes mellitus, smoking, Lp(а) concentrаtion (mediаn [interquаrtile rаnge]): 30 [11; 63] vs. 14 [5; 30] mg/dl, p<0.01) in the group with stenotic cаrotid аtherosclerosis in compаrison with control group. Besides, Lp(а) level wаs higher in CHD subgroup thаn in pаtients with stenotic cаrotid аtherosclerosis without CHD: 32 [12; 72] vs. 24 [8; 50] mg/dl, respectively, p=0.01. Elevаted (≥30 mg/dl) Lp(а) level, low moleculаr weight аpolipoprotein(а) [(LMW аpo(а)] phenotype were аssociаted with stenotic cаrotid аtherosclerosis (odds rаtio (OR) 2.9; 95% confidence intervаl (CI) 2.1-4.0, p<0.01 аnd OR 2.3; 95% CI 1.6-3.4, p<0.01, respectively). Logistic regression аnаlysis showed independent аssociаtion of elevаted Lp(а) level аnd LMW аpo(а) phenotype with stenotic cаrotid аtherosclerosis both in the presence аnd absence of CHD. The level of IgM аutoаntibodies to Lp(а) wаs higher in control group thаn in pаtients with stenotic cаrotid аtherosclerosis, p=0.02. Conclusion The level of Lp(a) ≥30 mg/dl and low molecular weight phenotype of aprotein(a) are predictors of stenotic atherosclerosis CA, regardless of the presence of coronary heart disease and other risk factors, while a reverse relationship was found between the level of autoantibodies of the IgM class against Lp(a) and the severity of atherosclerosis CA.

[The Relationship of the Concentration of Lipoprotein(a) and Markers of Inflammation with Multifocal Atherosclerosis in Women].

PURPOSE: to study relationship of lipoprotein(a) [Lp(a)], indicators of systemic inflammation and humoral immunity with severity of atherosclerotic involvement of various vascular beds in women. MATERIALS AND METHODS: We included in this study 148 women aged 69±11 years with results of instrumental investigation of coronary, carotid arteries, and arteries of lower extremities. According to results of coronary angiography and ultrasound study patients were distributed into two groups: with stenosing atherosclerosis (those with hemodynamically significant [>50%] atherosclerotic lesions in any of these vascular beds, n=108), and control (those without hemodynamically significant stenoses, n=40). In dependence of extent of atherosclerotic involvement patients with stenosing atherosclerosis were divided into subgroups: with lesions in one vascular bed (subgroup 1, n=44) and with lesions in two and more vascular beds (subgroup 2, n=64). All patients with stenosing atherosclerosis and 78% of control patients took statins. In all patients we measured lipid spectrum, Lp(a) concentration, C-reactive protein (CRP). Preparations of oxidized lipoproteins [oxLp(a)] were obtained by Cu2+-induced free radical oxidation at 37 °Ð¡ for 3 hours. Titer of autoantibodies to Lp(a), LDL and their oxidized modifications was determined by enzyme-linked immunosorbent assay (ELISA). Concentration of low-density lipoprotein cholesterol corrected on cholesterol in Lp(a) (LDLCh corr) was calculated by Dahlen modification of Friedewald formula. RESULTS: Stenosing atherosclerosis was diagnosed in 60 of 74 women (80%) with Lp(a) concentration above median - 33 mg/dl (in 38 multifical). Increase of blood serum Lp(a) concentration was associated with presence of isolated as well as multifocal atherosclerosis according to unifactorial, multifactorial, and logistic analysis, irrespective of other factors of risk and indicators of inflammation. According to results of logistic regression analysis increase of Lp(a) concentration by 1 mg/dl was associated with 1 % elevation of probability of appearance and development of multifocal atherosclerosis in women. Low level of class IgM autoantibodies to Lp(a) was linked with detection of stenosing atherosclerosis in any of 3 vascular beds (1st vs. 4th quartile of IgM autoantibodies concentration - OR 7.6., 95%CI 1.9-29.4; р=0.004) and had diagnostic significance. Indicators of systemic inflammation such as CRP and circulating immune complexes were high and had diagnostic significance for detection of multifocal atherosclerosis in studied women. However none of indicators was predictor of appearance of stenosing atherosclerosis according to data of logistic regression analysis. CONCLUSION: Elevated concentration of Lp(a) is an independent predictor of risk of development stenosing atherosclerosis in various vascular beds and appearance of multifocal irrespective of other risk factors, indicators of systemic inflammation, and factors of humoral immunity in women. Markers of inflammation, as well as IgM autoantibodies against Lp(a) have diagnostic value for detection of patients stenosing lesions ib one or several vascular beds.

The Association of Lipoprotein(a), Apolipoprotein(a) Phenotypes and Autoantibodies to Lipoprotein(a) With Lower Extremity Artery Disease.

AIM: Lipoprotein(a) [Lp(a)] and low molecular weight (LMW) apolipoprotein(a) [apo(a)] phenotype are risk factors of сoronary heart disease and stroke. Data about the role of Lp(a) and phenotypes apo(a) in the development of lower extremity artery disease (LEAD) is scarce. The aim of our study was to assess the association of Lp(a), apo(a) phenotypes and autoantibodies to apolipoprotein B100 (apoB100) lipoproteins with LEAD. MATERIALS AND METHODS: The study included 622 patients (386 male and 236 female, average age 61±12 years), examined in the Department of Atherosclerosis of National Medical Research Center of Cardiology. Patients were divided into 2 groups: the main group included 284 patients with LEAD, 338 patients without significant atherosclerosis of coronary, carotid and lower limbs arteries formed the control group. LEAD was diagnosed as atherosclerotic lesions with at least one stenosis of low limb artery ≥50 % and ankle-brachial index ≤0.9. The concentration of Lp(a), lipids was measured in blood serum of all the patients, level of autoantibodies to apoB100 lipoproteins was measured in 247 patients, and apo(a) phenotypes were determined in 389 patients. RESULTS: Patients with LEAD were older, were more frequently male, and had a greater prevalence of risk factors including hypertension, type 2 diabetes, smoking than the control group patients (p<0.001 in all the cases). The level of Lp(a) was significantly higher in the main group compared to control group: 35 [14; 67] mg / dl vs. 14 [5; 32] mg / dl, p<0,001. ROC analysis demonstrated that the level of Lp(a) ≥26 mg / dl was associated with LEAD (sensitivity 61 %, specificity 70 %). The prevalence of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype were higher in the main group in comparison with the control group: 61 % vs. 30 % and 48 % vs. 26 % respectively (p<0.001 in the both cases). The odds ratio of LEAD in the presence of Lp(a) ≥26 mg / dl was 3.7 (95 % confidence interval (CI), 2.6-5.1, p<0.001) and in the presence of LMW apo(a) phenotype was 2.6 (95 % CI, 1.7-4.0, p<0.001). In logistic regression analysis adjusted for age, sex, hypertension, smoking, diabetes, both Lp(a) and LMW apo(a) phenotype were independent predictors of LEAD when included separately. The level of IgM autoantibodies to Lp(a) was significantly higher in the control group compared to the patients with LEAD (p=0.01). Concentration of IgG autoantobodies to Lp(a) and LDL in the plasma did not differ essentially in the both groups. CONCLUSION: The level of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype are independent predictors of LEAD, whereas the contribution of autoantobodies to Lp(a) in LEAD development is controversial.

[Lipoprotein(a), its autoantibodies, and circulating T lymphocyte subpopulations as independent risk factors for coronary artery atherosclerosis]. / Lipoproteid(a), autoantitela k nemu i tsirkuliruyushchie subpopulyatsii T-limfotsitov kak nezavisimye faktory riska ateroskleroza koronarnykh arterii.

AIM: To study the role of lipoprotein(a) [Lp(a)] as a potential autoantigen causing the activation of immunocompetent cells in atherosclerosis. SUBJECTS AND METHODS: A total of 104 men with stable coronary artery (CA) disease and different degrees of progressive coronary atherosclerosis were examined. Clinical blood analysis was carried out and lymphocyte subpopulations (CD4+, Th1, Th17, and Treg) were determined using immunofluorescence and flow cytometry. In addition, the indicators of blood lipid composition, Lp(a), autoantibody (autoAb) titer to Lp(a), and low-density lipoproteins (LDL), and the lymphocyte activation marker sCD25 were also measured. RESULTS: The Lp(a) level was shown to predict the severity of CA lesions (ß=0.28, p<0.05), regardless of age, the level of cholesterol, different T-lymphocyte subpopulations, sCD25, and autoAb. A combination of the concentration of Lp(a) above 11.8 mg/dl, that of Th17 over 11.4∙103 cells/ml and the reduced levels of regulatory T cells and IL-10-producing CD4+ T cells showed a manifold increase in the risk of severe and progressive CA atherosclerosis. There was a direct correlation of the blood level of Th1 with that of IgG autoAb specific to all atherogenic apoB-containing lipoproteins, including Lp(a). There was an inverse correlations of the lymphocyte activation marker sCD25 with IgM anti-Lp(a) autoAb titers (r=-0.36; p<0.005), but this was less significant with autoAbs to native and oxidized LDL (r=-0.21 and r=-0.24; p<0.05, respectively). CONCLUSION: The slightly elevated Lp(a) concentration along with changes in the level of T lymphocyte subpopulations was first shown to significantly potentiate the risk of progressive and multiple CA lesion in the examinees. The correlation of IgM anti-Lp(a) autoAb with the lymphocyte activation marker sCD25 and that of IgG anti-Lp(a) autoAb with Th1 have demonstrated that Lp(a) is involved in the autoimmune inflammatory processes in atherosclerosis.