Kuvikova I. Hyperhomocysteinemia and associated with it metabolic disorders as risk factors for vascular damage in patients with antiphospholipid syndrome

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0418U002371

Applicant for

Specialization

  • 14.01.12 - Ревматологія

17-04-2018

Specialized Academic Board

Д 11.600.04

Donetsk National Medical University

Essay

Subject of research – antiphospholipid syndrome (APS); objective – to improve diagnostic efficiency of cardiovascular pathology in patients with APS by studying hyperhomocysteinemia (HHC) role as well as associated metabolic, vascular and genetic factors in the development of structural and functional changes in vessels; methods – clinical examination, biochemical, elecrochemiluminescence immunoassay, enzyme immunoassay, microbiological, polymerase chain reaction, instrumental methods, mathematical methods for statistical analysis of the data obtained; scientific novelty and results – HHC incidence in the patients with APS, its relationships with various factors (5,10-MTHFR genetic polymorphism, dyslipidemia, vitamin В9 and В12 status, systemic inflammation markers), the course of the disease and structural and functional changes in the cardiovascular system were first evaluated; high HHC frequency rate (32.4% – 52.1 %) was found in the patients with primary antiphospholipid syndrome and secondary antiphospholipid syndrome, being associated with arterial hypertension, smoking, high CRP and IL-6 levels, antibodies to cardiolipin and beta-2-GP-1, male sex; the role of vitamins В9 and В12 status as well as 5, 10-MTHFR genetic polymorphism in HHC development was determined, and HHC was demonstrated to be an independent risk factor for cardiovascular diseases, unrelated to dyslipidemia; the prevalence of genetic polymorphism of 5, 10-MTHFR gene at nucleotide 677 in the patients with different variants of APS was first investigated in Ukraine, its relationship with vitamins status, antiphospholipid antibodies, inflammation markers, lipidosis and vascular disease was estimated; vitamins В9 and В12 supply in the patients with APS was evaluated, and deficiency of vitamins В9 and В12 was found to be associated with of HC, CRP and IL-6 levels, to a lesser extent – with age and lipid contents; vitamins В9 and В12 deficiency, their combined deficiency in particular, was demonstrated to be associated with structural and functional cardiac status in majority of patients; the concentration of soluble thrombomodulin and endotheline-1 was found to be early markers of endothelium damage in the patients with APS because of their close association with subclinical manifestations of atherosclerotic vascular disease; the levels of soluble thrombomodulin and endotheline-1 were shown to be closely associated with HHC, deficiency of vitamins В12 and В9, hyperproduction of antibodies to cardiolipin and beta-2-GP 1, and in secondary APS patients – with high disease activity as well; the results of the study are of great significance for clinical practice because of the determination of laboratory and diagnostic complex measures for examination of the patients with APS, promoting the detection of the patients with increased risk of vascular lesions; introduction – diagnostic and treatment work of Department of non-coronary heart diseases and rheumatology of state institution “National Scientific Center “Strazhesko Institute of Cardiology” of Ukrainian NAMS”, Vinnytsia Regional Pirogov Memorial Clinical Hospital, Research Institute of Rehabilitation of Vinnytsia National Pirogov Memorial Medical University, is used in educational process of Departments of Internal Medicine No 1, 2, 3 and Department of Clinical Pharmacology at Vinnytsia National Pirogov Memorial Medical University, Department of Internal Medicine No 2 at state higher education institution “Ternopil State Gorbachevskyi Memorial Medical University”; scope of use – diagnosis and treatment at departments of rheumatology and therapy, educational process at the chairs of therapy of medical educational institutions.

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