cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-2157Research ArticleАРТЕРИАЛЬНАЯ ГИПЕРТОНИЯARTERIAL HYPERTENSIONПротивовоспалительные эффекты блокады ангиотензиновых рецепторов 1 типа у пациентов с гипертензией и сосудистым микровоспалениемAnti-inflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammationФлизерД.FliserDanilo

Department of Internal Medicine

Department of Internal Medicine

BuchholzKonradBuchholzKonrad

Department of Internal Medicine

Department of Internal Medicine

HallerHermannHallerHermann

Department of Internal Medicine

Department of Internal Medicine

Medical School Hannover, HannoverГерманияMedical School Hannover, HannoverGermany201001011970971420Copyright © Флизер Д., Buchholz K., Haller H., 19701970Флизер Д., Buchholz K., Haller H.Fliser D., Buchholz K., Haller H.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/2157

Введение: Ранее выполненные экспериментальные исследования продемонстрировали наличие провоспалительных свойств у ангиотензина II (АТII). Поэтому была проведена оценка противовоспалительного эффекта блокатора ангиотензиновых рецепторов (БРА) 1 типа олмесартана медоксомила, в виде монотерапии и в сочетании с ингибитором ГмГ-КоА редуктазы правастатином у пациентов с эссенциальной гипертензией (ЭАГ) и сосудистым микровоспалением. Методы и результаты. Оценивалась динамика маркеров сосудистого воспаления, в т.ч. высокочувствительного С-реактивного белка (вчСРБ), а также изменения липидного профиля на фоне 12-недельной терапии олмесартаном (n=100) либо плацебо (n=99) в рамках многоцентрового, проспективного, двойного слепого исследования. На 6 нед. в обеих группах (гр.) терапии дополнительно назначался правастатин. Контроль артериального давления (АД) достигали за счет дополнительного приема гидрохлортиазида (Гхт). К 6 нед. лечения в гр. олмесартана отмечалось достоверное снижение сывороточных уровней вчСРБ (-15,1 %; р<0,05), высокочувствительного фактора некроза опухолей альфа (вчФНОα) (-8,9 %; р<0,02), интерлейкина-6 (ИЛ-6) (- 14,0 %; р<0,05) и моноцитарного хемотаксического протеина-1 (-6,5 %; р<0,01). В гр. плацебо снизилось АД, однако не регистрировалось одновременного уменьшения концентраций воспалительных маркеров. Через 12 нед. терапии наблюдалось дальнейшее снижение уровней вч СРБ (-21,1 %; р<0,02), вчФНОα (-13,6 %; р<0,01) и ИЛ-6 (-18,0 %; р<0,01) на фоне лечения комбинацией олмесартана и правастатина. При приеме только правастатина (в гр. плацебо) достоверное изменение концентраций маркеров воспаления отсутствовало. Добавление правастатина приводило к значимому (р<0,001) снижению уровня холестерина липопротеидов низкой плотности как в гр. олмесартана (-15,1 %), так и в гр. плацебо (-12,1 %). Заключение. Блокада ангиотензиновых рецепторов приводит к достоверному снижению интенсивности сосудистого микровоспаления уже на 6 нед. терапии у пациентов с ЭАГ. Благоприятные сердечно-сосудистые эффекты БРА к АТ могут быть отчасти обусловлены противовоспалительным действием этих препаратов.

Background: Experimental studies revealed pro-inflammatory properties of angiotensin II. We evaluated antiinflammatory effects of the angiotensin II subtype 1 receptor antagonist olmesartan medoxomil alone and in cotherapy with the HMG-CoA reductase inhibitor pravastatin, in patients with essential hypertension and microinflammation. Methods and results: We measured a panel of vascular inflammation markers, including high-sensitivity C-reactive protein (hsCRP), and lipid levels during 12 weeks of therapy with olmesartan (n=100) or placebo (n=99) in a prospective double-blind multicenter study. Pravastatin was added to the double-blind therapy at week 6 in both treatment arms. Blood pressure (BP) control was achieved with addition of hydrochlorothiazide. Olmesartan treatment had already significantly reduced serum levels of hsCRP (-15,1%; p<0,05), high-sensitivity tumor necrosis factor-alpha, hsTNF-alpha (-8,9%; p<0,02), interleukin-6, IL-6 (-14,0%; p<0,05), and monocyte chemotactic protein-1, MCP-1 (-6,5%; p<0,01) after 6 weeks of therapy, whereas placebo treatment (ie, BP reduction) had no major effect on inflammation markers. After 12 weeks of therapy, hsCRP (-21,1%; p<0,02), hsTNF-alpha (-13,6%; p<0,01), and IL-6 (-18,0%; p<0,01) decreased further with olmesartan and pravastatin co-therapy, but treatment with pravastatin alone (ie, co-therapy with placebo) did not significantly alter inflammation markers. In contrast, addition of pravastatin led to a significant (p<0,001) reduction in LDL cholesterol serum concentrations in the olmesartan and placebo treatment groups (-15,1% and -12,1%, respectively). Conclusions: Angiotensin II receptor blockade significantly reduces vascular microinflammation in patients with essential hypertension by as early as week 6 of therapy. This anti-inflammatory action of angiotensin II receptor antagonists may contribute to their beneficial cardiovascular effects.

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The authors declare that there are no conflicts of interest present.