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5THE STUDY OF ENDOTHELIAL FUNCTION OF BLOOD VESSELS IN ANCA-ASSOCIATED VASCULITIS
Suiarko V. I.
Pomazan D. V MD., PhD, Professor Syniachenko O. V. MD., PhD, Professor Iermolaieva M. V.
MD., PhD, Associate Professor Iegudina E. D.
Ukraine, Lyman, Donetsk National Medical University, Department of Internal Medicine №1
Abstract. Clinical and pathogenetic relationship between ANCA-associated vasculitis and endothelial dysfunction of blood vessels has not been studied. To assess the relationship between disease course of systemic vasculitis with endothelial function of vessels in 129 patients (76 with microscopic polyangiitis, 26 with Wegener's granulomatosis with polyangiitis and 27 with eosinophilic granulomatosis with polyangiitis Churg-Strauss) biochemical and ELISA methods the studied parameters in blood of endothelial function of blood vessels (levels of endothelin-1, thromboxane-A2, homocysteine, prostacyclin, nitrite, cyclic guanosine monophosphate). The imbalance of the levels of vasoconstrictors and vasodilators in the blood, which is manifested by increased concentrations of endothelin-1 and nitrite with a reduction in the content of prostacyclin and of homocysteine. This shows the endothelial function of blood vessels in systemic vasculitis, which are involved in the pathogenesis of diseases.
Keywords: endothelial function, ANCAs, vasculitis, granulomatosis, polyangiitis.
Introduction. ANCA-associated vasculitis have a significant health and social harm to society. It is known that ANCA-associated vasculitis belongs with Wegener's granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis Churg-Strauss (EGPA) and microscopic polyangiitis (MPA) [2]. The prevalence of GPA is 24 persons per 10 thousand population, MPA - 13 to 10 thousand [11, 12], and EGPA is 0.5 per 100 thousand population [10]. GPA and MPA together make a group of "systemic necrotizing vasculitis" [6]. The pathogenesis of ANCA-associated vasculitis insufficiently investigated [1, 4, 5]. A certain importance is attached to the violation of the endothelial function of blood vessels [7]. It is believed that these patients have a high synthesis of proinflammatory cytokines enhances apoptosis of endothelial cells of small vessels with subsequent alteration of their functions [8]. There is evidence that violations of endothelial function of blood vessels can be most typical for patients with GPA [9].
Aim of this study: to investigate the changes of parameters of endothelial function of blood vessels in patients with MPA, GPA and EGPA.
Materials and methods. The study included 129 patients (47% men and 53% women) with ANCA- associated vasculitis 76 (59%) of the MPA at the age of 44.0±1.53, 26 (20%) with GPA at the age of 46.6±2.55 years and 27 (21%) with EPA at the age of 42.1±2.74 years. The disease duration from the time of his manifestation in patients suffering from MPA was 5.7±0.75 years, with GPA - 4.4±0.88 years, with EGPA - 10.5±1.98 years. 1st degree of activity of the disease occurred in 10% of patients with ANCA- associated vasculitis, 2nd - 35%, 3rd - 55%, and examined with MPA, GPA, and EGPA did not differ among themselves. Kidney failure was diagnosed in 73% of cases, lung in 63%, skin - 61%, joint -54%, infarction - 49%, liver - 47%, nervous system - 46%, endocardial and valvular in 36%.
ANCAs in the serum were detected in 74% of patients with MPA, 79% with GPA and 44% with EGPA. Antibodies against myeloperoxidase (MPO) was present in 88% of cases of ANCAs in 65% of the number examined MPA, at GPA - respectively 27% and 21%, EGPA 100% and 44%, whereas antibodies against proteinase-3 (AP3), respectively 35% and 26% of cases of MPA, 100% and 79% GPA, 13% and 6% EGPA. The ratio of AMP on the frequency of detection of ANCA- associated vasculitis made up as "MPA:EGPA:GPA=3:2:1" and AP3 as "MPA:EGPA:GPA =14:5:1". The level of eosinophils in the blood of patients EGPA was 15.2±2.17% of the number of leukocytes or 2.1±0,88 106/1.
Endothelial function of blood vessels was assessed by levels of serum endothelin-1 (ET-1), thromboxane A2 (TxA2), homocysteine (HCys), prostacyclin (PGI2), nitrite (NO2) and cyclic guanosine monophosphate (cGMP). For definitions of these indicators used by the reader "PR2100-Sanofi Diagnostics Pasteur" (France), the concentration of NO2 (stable end product of the metabolism of nitric oxide) were studied by spectrophotometry ("SF-46", Russia), and antibodies against
myeloperoxidase and AP3 - immunoblotting techniques ("Euroline-Euroimmun", Germany). As a control, we examined 30 healthy individuals (12 men and 18 women aged from 18 to 58 years).
Statistical processing of the results of research conducted by computer variation, correlation, regression and analysis of variance (program "Microsoft Excel" and "Statistica-Stat Soft", USA). Estimated mean values (M), standard deviations (SD) and errors (m), correlation coefficients, the criteria of multiple regression, dispersion (D), Student's Z-test (t) and the reliability indicators (p).
Results. In patients with ANCA- associated vasculitis indicators ET-1 8.6±0,13 PG/ml, TxA2 of 9.5±0,24 ng/ml, and HCys and 5.6±0,21 mmol/l, PGI2 - 23,3±0,92 ng/ml of NO2 is 5.7±0,11 mmol/l and cGMP - 11.7 of±0.23 pmol/ml. In comparison with indicators of healthy people in the control group, there is reliability (p<0.001) increase ET-1 in 2.2 times (t=22,39), NO2 of 12% (t=3,80), decrease PGI2 of 68% (t=a 7.45), HCys of 40% (t=8,67).
MPA is accompanied by an increase in blood ET-1 in 2.1 times, NO2 of 8%, cGMP of 12% and decrease of HCys of 42% and PGI2 of 67%, (<M±SD> healthy), respectively, observed in 96%, 45%, 55%, 68%, 32%. For GPA is characterized by increased content in the blood ET-1 in 2.2 times and NO2 of 94%, while reducing the concentration of HCys by 31%, PgI2 74% cGMP and 40%, respectively, noted in 92%, 85%, 58%, 62% and 54% of cases. Much like MPA, EGPA characterized increase blood ET-1 in 2.2 times against the background of reduction of HCys levels of 43% and PGI2 of 67% of that detected in 100%, 78% and 33% of cases. Thus, MPA, GPA and EGPA differ accordingly increased, reduced and unchanged indicators cGMP, and EGPA parameters of nitrite (NO2).
Myocardial damage in MPA has a dispersive effect on the blood levels of HCys, which depends on changes of the endocardium and valvular heart. Average values of endothelial function in patients with MPA, with and without cardiopathy such differ little among themselves. Changes in the endocardium and valvular heart determine the concentration in the blood of patients EGPA cGMP, although the presence in these patients of cardiopathy affects the averages in the blood HCys, in cases of heart disease are reduced by 30% (t=2,99, p=0,007).
In patients with MPA is observed the dispersion effect of systolic dysfunction of the left ventricle blood levels of NO2, and the diastolic of cGMP. Patients with EGPA on the condition of the valvular apparatus have an effect on the concentration TxA2 and HCys on the size of the heart chambers - parameters endothelin. In EGPA changes the electrical conductivity of the heart depend on the parameters of PGI2 (D=equal to 19.71, p=0.001), the condition of the valvular apparatus is closely associated with concentrations TxA2 (D=4,35, p=0.049) and HCys (D=9,16, p=0,007), and the size of the heart chambers affected by the level endothelin (D=7,37, p=0,013)/
According to ANOVA, parameters of end-diastolic volume of the right ventricle (D=7,15, p=0,013) and pulmonary vascular resistance (D=13,99, p=0.001) in MPA depends on the level of HCys, the size of the left atrium of the values of PGI2 (D=3,56, p=0,048), ejection fraction of blood the left ventricle of NO2 (D=2.87, p=0,047). There is a dispersive effect on end-diastolic volume of the left ventricle in patients with GPA levels in the blood of TxA2 (D=4,81, p=0.037) and PGI2 (D=4,15, p=0,048, end-diastolic volume ET1 (D=9,19, p=0,013), size of the right ventricle - HCys and NO2 (respectively D=8,11, p=0.015 and D=20,84, p=0.001). When EGPA myocardial mass of the left ventricle depends on the rate prostacycline (D=2,86, p=0,048), the size of the right ventricle from the blood level of cGMP (D=4,39, p=0,048), pulmonary vascular resistance parameters endothelin (D=6,06, p=0,004) and NO2 (D=5,41, p=0.006), the value of the diameter of the brachial artery during the period of vasodilatation from concentration ET-1 and TxA2 (respectively D=5,83, p=0.027 and D=8,35, p=0,010).
Conclusions: in patients with ANCA- associated vasculitis on the observed a significant impairment of endothelial function, which are accompanied by an imbalance of vasoconstrictors and vasodilators. Certain types of ANCA - associated vasculitis are improving (MPA), low (GPA) and unmodified (EGPA) indicators of cGMP, a long time values of NO2 in EGPA. Endothelial function is dependent on the damage to the heart, and participates in the pathogenesis of arrhythmias, myocardial dysfunction, changes in the size of the heart chambers.
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ВЛИЯНИЕ РАЗЛИЧНЫХ ВИДОВ МЕДИКАМЕНТОЗНОЙ ТЕРАПИИ, НАПРАВЛЕННОЙ НА КОРРЕКЦИЮ ФАКТОРОВ СЕРДЕЧНО-СОСУДИСТОГО РИСКА, НА СЕРДЕЧНО-ЛОДЫЖЕЧНЫЙ СОСУДИСТЫЙ ИНДЕКС
к. мед. н. Удовиченко Марина Михайловна, д. мед. н. Рудык Юрий Степанович
Украина, Харьков, ГУ «Национальный институт терапии им. Л.Т.Малой НАМН Украины»
Abstract. Arterial stiffness relates to the pathological changes in the arteries and can reflect the presence of arteriosclerosis. In clinical practice, the reliable parameters of arteriosclerosis or injuries of arterial wall are absent. The novel index, such as cardio-ankle vascular index (CAVI) can be used for arterial stiffness assessment and level of arteriosclerosis monitoring. CAVI reflect the stiffness of the arterial bed from aorta to ankle and may reflect, as it was mentioned above, the degree of arteriosclerosis development. Perhaps this is why CAVI significantly increases in patients with cardiovascular risk factors and modification of these factors can lead to the improvement of CAVI values. From this perspective, the use of different groups of antihypertensive, hypoglycemic, lipid-lowering drugs, which leads to CAVI changes, is very perspective.
This paper reviews the rationale of different antihypertensive, hypoglycemic, lipid-lowering drugs use and lifestyle-changing strategy regarding their influence on CAVI and discusses the issues about implementation it in routine clinical practice not only for cardiovascular risk in addition to the traditional risk factors estimation but also for the evaluation of therapy efficacy.
Keywords: arterial stiffness, arteriosclerosis, cardio-ankle vascular index, cardiovascular risk factors, therapy.
