Prospects of using genetic testing to increase the effectiveness of antihypertensive therapy

Aim. To compare the effects of 3-month therapy with a fixed-dose combination of an angiotensin-converting enzyme inhibitor (perindopril) and a thiazide-like diuretic (indapamide) in genetically heterogeneous subgroups of patients with hypertension (HTN) for assessing the prospects of using genetic testing for choosing the antihypertensive treatment regimen.Material and methods. Forty-one patients with grade 1-2 HTN with insufficient effectiveness of previous antihypertensive therapy and 20 healthy individuals were examined to compare the prevalence of gene polymorphism in the Rostov Oblast. Patients with HTN underwent standard diagnostic tests, as well as a molecular genetic test to determine the most clinically significant polymorphic genes involved in the pathogenesis of HTN.Results. A relationship was found between the clinical and morphofunctional characteristics of HTN in patients with polymorphisms of AGT, AGTR2, CYP11B2, GNB3, and NOS3 -786 genes, of which 3 polymorphic genes (AGT, AGTR2, CYP11B2) encode the activity of the angiotensin-converting enzyme. The effectiveness of using a combination of renin-angiotensin-aldosterone system inhibitor agent with a thiazide-like diuretic as an initial antihypertensive therapy was evaluated.An analysis showed that fixed-dose combination of perindopril (10,0) and indapamide (2,5) (Noliprel A Bi-forte) in genetically heterogeneous subgroups of HTN patients displays a more pronounced antihypertensive and organ-protective effects in individuals with the mutant allele 704C of AGT T704C polymorphism. A significant decrease in blood pressure was demonstrated according to standard 24-hour monitoring (p<0,05). A significant decrease in the left ventricular mass index (p=0,0001), as well as a significant increase in the ratio of peak mitral flow velocity in early and late diastole (VE/VA) (p=0,0024) were showed. There was a positive effect of therapy on arterial stiffness parameters: a decrease of the pulse wave velocity (p=0,0035), vascular age (p=0,00002) and reflection index (Ri) (p=0,000001), compared with noncarriers of mutant allele 704C of AGT gene.Conclusion. The results obtained indicate the promise of using genetic approaches to develop a personalized drug treatment strategy for HTN patients in order to increase its effectiveness

IVABRADINE INFLUENCE ON SYSTOLIC AND DIASTOLIC FUNCTION OF HEART VENTRICLES IN PATIENTS WITH ISCHEMIC HEART DISEASE AFTER PRIMARY REVASCULARIZATION

Aim. To compare effects of different medication therapy schedules on parameters of systolic and diastolic function of the left (LV) and right (RV) ventricles in patients with ischemic heart disease (CHD) after primary revascularization of myocardium (PPCI).Material and metods. The study was performed on two groups of CHD patients (n=32 and n=30, resp.) before and after PPCI. Systolic and diastolic function were assessed by ultrasound methods including doppler. In the 1st group during post-surgery period due to impossibility to titrate dosage of β-adrenoblokers and, respectively, achievement of CHD target heartrate, standard therapy was improved by ivabradin in dose 10-15 mg/day during 3 months.Results. Before operation in CHD patients’ diastolic dysfunction of LV and RV prevailed. PPCI and consequent medication therapy led to improve of systolic function of the LV and RV in both groups, however in the group additionally received ivabradin dynamic of the parameters was more prominet. In the 1st group, in contrast to 2st, also there was normalization of diastolic function of both ventricles.Conclusion. Adding of ivabradine to standard therapy of CHD patients after PPCI fulfills the efficacy for systolic LV and RV function and leads to normalization of their diastolic function

Arterial hypertension in tuberculosis patients: clinical course and pharmaceutical control

Aim. To access arterial hypertension (AH) prevalence, pathogenesis, and effectiveness of fixed-dose perindopril and indapamide combination in tuberculosis (TB) patients. Material and methods. In total, 489 case records of patients with TB of various localization were analyzed; 42 patients with TB and AH were examined. Dynamics of 24-hour blood pressure monitoring (BPM) parameters, left ventricular (LV) morphology and function (echocardiography data), vegetative effects on hemodynamics (heart rate variability), and endothelial function (von Willebrand factor level measurement, reactive hyperemia test) were investigated. Results. The rates of AH and TB combination were quite high. These patients were characterized by “non-dipper” and “night-peaker” 24-hour BMP profiles, hypersympathicotonia, LV remodeling, right heart hypertrophy tendency, and endothelial dysfunction. Twelve-week therapy with fixed-dose combination of perindopril (4,0 mg) and indapamide (1,25 mg) was associated with positive dynamics of pathogenetic disturbances in AH and TB patients. Conclusion. AH and TB combination negatively affects cardiovascular system. Treatment with perindopril and indapamide combination provides antihypertensive effect and normalizes main mechanisms of BP regulation