Introduction. Obesity is becoming one of the leading risk factors of coronary heart disease, hypertension, cerebrovascular disease. Despite the presence of a large number of antihypertensive agents and scientific substantiation of antihypertensive treatment principles it would be wrong to assume that the problem is completely solved. Development of endothelial dysfunction is one of the key pathogenic mechanisms in hypertension. This process is proven to have contributed by immune inflammation activation which is mediated by pro-inflammatory cytokines and oxidative stress. Aims. To investigate the additional benefits of the combined antihypertensive therapy with lacidipine and candesartan on the basis of studying their antioxidant properties, impact on endothelial function and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. Methods. A combination of a calcium channel blocker and angiotensin receptor blocker (lacidipine 2 mg, 4 mg, and candesartan 4mg, 8mg, 16mg) was prescribed to 30 patients with essential hypertension of grades 1-3, 30 to 65 years old (mean age - 54.7 ± 5.8 years), who previously have not been receiving regular antihypertensive therapy. Results. During the course of combined antihypertensive therapy with lacidipine and candesartan, a significant reduction in i-NOS activity, TNF-α to its type I soluble receptor ratio (TNF- α/sTNF-αRI), and oxidative stress marker - 8-iso-PgF2α has been observed. Activity of e-NOS, levels of SOD and catalase, in contrast, have increased by the end of observation period. Conclusion. The improvement of endothelial function due to lower level of oxidative stress and a significant decrease of immune activation has been observed in hypertensive patients with overweight and obesity under the influence of combined antihypertensive therapy with lacidipine and candesartan.

Hypertension in its origin is a heterogeneous and multisystemic disease. Evaluation of oxidative stress activity based on the level of 8-iso-PgF2α, proinflammatory activity based on tumour necrosis factor-α, its type I soluble receptor, and C-reactive protein levels is relevant for further understanding of pathogenesis of hypertension and improvement of the early diagnostics of heart failure. 186 hypertensive patients were observed during a 2-months course of treatment, aged 30 to 65 years. Serum levels of 8-iso-PgF2α (n = 34), tumour necrosis factor-α and its type I soluble receptor were determined by ELISA before and after course of treatment. C-reactive protein level was determined by biochemical method. The control group included 16 clinically healthy individuals, aged 27 to 55 years. Hypertensive patients enrolled into the study were randomized into three groups that received different protocols of combined anti-hypertensive therapy: I clinical group – а combination of bisoprolol and indapamid, II – а combination of lacidipine and candesartan, III – а combination of fosinopril sodium and hydrochlorothiazide. On the background of combined antihypertensive therapy, we observed favourable dynamics of 8-iso-PgF2α, tumour necrosis factor-α and its type I soluble receptor, and C-reactive protein levels. Taking into account the insignificance of the correlations revealed, a one-factor dispersion analysis was applied which allowed us to determine the influence of the grade and duration of hypertension on the dynamics of the studied parameters. It has been found that the grade of hypertension is related to an increase in TNF-α and 8-iso-PgF2α serum levels, but not in TNF-α type I soluble receptor, and the duration of hypertension is related to an increase in C-reactive protein, TNF-α and its type I soluble receptor levels, with no relation to the level of 8-iso-PgF2α. Thus, oxidative stress possibly promotes the activation of potentially damaging immune mechanisms mediated by proinflammatory cytokines, nonspecific inflammation and drives the further progression of lesions in the target organs.

The review article presents the pathogenetic role of atherosclerotic vascular lesions in the development of cardiovascular diseases. The relationship between atherosclerosis and inflammation, which is characterized by the identical mechanism in the early phases, which includes the enhancement of the interaction between the vascular endothelium and circulating leukocytes is shown. The definition of such concepts as dyslipidemia, hyperlipoproteinemia and hyperlipidemia is given. The classification of hyperlipoproteinemia by Fredrickson, the clinical classification of dyslipidemia, proposed by the Ukrainian Scientific Society of Cardiologists, 2011 is considered. The correction of dyslipidemia, by both non-medicamentous measures, and drug treatment according to different variants of dyslipidemia is shown. The main groups of lipid-lowering drugs are listed. Their main mechanisms of action to reduce blood lipid levels are noted, and their side effects are listed. General recommendations are given on the monitoring of lipids and liver enzymes in patients taking lipid-lowering therapy.

The main cardiovascular diseases affect the processes of myocardial remodeling, which further contributes to the formation of systolic or diastolic heart dysfunction. The formation of myocardial dysfunction is primarily associated with left ventricular hypertrophy when under hemodynamic loading, firstly, wall rigidity increases, secondly, myocardial fibrosis is formed. The latter is one of the key factors of the hypertrophic process caused by the accumulation of collagen, which leads to a aggravation of the left ventricle relaxation processes. Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that are clinically manifested by alterations in the size, shape, and function of heart as a result of the heart muscle injury. It has been determined that fibrosis is an early morphological sign of injury in patients with left ventricular overload, as well as a factor in the development of diastolic and systolic dysfunctions. Compensatory left ventricular hypertrophy transforms into heart failure due to the fibrosis development. In hypertrophy the content of elastic collagen type III decreases and rigid collagen type I increases. The essential role of the extracellular matrix in myocardial fibrosis formation is emphasized. Cardiac fibrosis is a process of pathological remodeling of the extracellular matrix, which leads to abnormalities in its composition and dysfunction of the heart muscle. The extracellular matrix plays a key role in organogenesis and post−traumatic healing in tissue injuries. The study of intercellular interactions of the extracellular matrix will provide a better understanding of the mechanisms of changes in geometry and function of the heart, and investigation of the activity of matrix components will open new opportunities for targeted therapeutic effects on molecular mechanisms of cardiac remodeling. Key words: diastolic dysfunction, extracellular matrix, myocardial fibrosis, cardiomyocytes, fibroblasts.

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