Abstract

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.

Highlights

  • артериальной гипертонией (АГ) — артериальная гипертония, АД — артериальное давление, AGT — ангиотензиноген, ADD1 — альфа аддуцин, AGTR1 — рецептор ангиотензина II типа 1, AGTR2 — рецептор ангиотензина II типа 2, ингибитор ангиотензинпревращающего фермента (иАПФ) — ингибиторы ангиотензинпревращающего фермента, CYP11B2 — альдостерон синтазы, GNB3 — b-субъединицы 3 G белка, NOS3 — эндотелиальной NO-синтазы, индекса массы миокарда левого желудочка (ИММЛЖ) — индекс массы миокарда левого желудочка, ЛЖ — левый желудочек, ренин-ангиотензин-альдостероновой систе­ ­мы (РААС) — ренин-ангиотензин-альдостероновой системы, СПВ — скорость пульсовой волны, суточное мониторирование АД (СМАД) — суточное мониторирование артериального давления, ЭхоКГ — эхокардиография, ЭКГ — электрокардиография

  • 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

  • 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

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Summary

Introduction

АГ — артериальная гипертония, АД — артериальное давление, AGT — ангиотензиноген, ADD1 — альфа аддуцин, AGTR1 — рецептор ангиотензина II типа 1, AGTR2 — рецептор ангиотензина II типа 2, иАПФ — ингибиторы ангиотензинпревращающего фермента, CYP11B2 — альдостерон синтазы, GNB3 — b-субъединицы 3 G белка, NOS3 — эндотелиальной NO-синтазы, ИММЛЖ — индекс массы миокарда левого желудочка, ЛЖ — левый желудочек, РААС — ренин-ангиотензин-альдостероновой системы, СПВ — скорость пульсовой волны, СМАД — суточное мониторирование артериального давления, ЭхоКГ — эхокардиография, ЭКГ — электрокардиография. 1. Динамика показателей АД по данным СМАД на фоне лечения у больных с наличием и отсутствием “мутантной” аллели полиморфного маркера T704C гена AGT.

Results
Conclusion

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