rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2017-13-3-383-390rpcardio-1490Research ArticlePOINT OF VIEWТОЧКА ЗРЕНИЯANGIOTENSIN RECEPTOR BLOCKERS WITH PLEIOTROPIC PROPERTIES: A NEW STANDARD IN CARDIOVASCULAR RISK MANAGEMENT AND TREATMENT OF HYPERTENSIONСОСУДИСТЫМИ РИСКАМИ И ЛЕЧЕНИИ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИПодзолковВ. И.PodzolkovV. I.

Подзолков Валерий Иванович – д.м.н., профессор, зав. кафедрой факультетской терапии №2 лечебного факультета, директор терапевтической клиники Университетской клинической больницы №4

Valery I. Podzolkov - MD, PhD, Professor, Head of Chair of Faculty Therapy N2, Director of the Therapeutic Clinic of University Clinical Hospital №4

ПисаревМ. В.PisarevM. V.

Писарев Михаил Владимирович – к.м.н., доцент кафедры факультетской терапии №2 лечебного факультета 

119991, Москва, ул. Трубецкая, 8 стр. 2

 Mikhail V. Pisarev - MD, PhD, Associate Professor, Chair of Faculty Therapy N2 

Trubetskaya ul. 8-2, Moscow, 119991

pisarev@gmail.comПервый Московский государственный медицинский университет им. И.М. СеченоваРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation201704072017133383390Copyright © Podzolkov V.I., Pisarev M.V., 20172017Подзолков В.И., Писарев М.В.Podzolkov V.I., Pisarev M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/1490

An increase in the activity of the renin-angiotensin-aldosterone system is one of the most important mechanisms for the realization of the cardiovascular continuum. The role that angiotensin receptor blockers play in achieving target figures of blood pressure and reducing cardiovascular risk is discussed. The importance of pleiotropic properties of angiotensin receptor blockers (in particular, activation of peroxisome proliferator-activated receptors gamma – PPAR-γ) in the management of patients with insulin resistance, obesity, dyslipidemia is also covered. The evidence base for the use of telmisartan as a drug with pleiotropic effect in patients with arterial hypertension and associated diseases (diabetes mellitus, obesity, renal dysfunction) is discussed. 

Повышение активности ренин-ангиотензин-альдостероновой системы – один из важнейших механизмов реализации сердечно-сосудистого континуума. Рассматривается роль, которую блокаторы рецепторов ангиотензина играют в достижении целевых цифр артериального давления и снижении сердечно-сосудистого риска. Освещается значение плейотропных свойств блокаторов рецепторов ангиотензина (в частности, активации гамма рецепторов, активируемых пероксисомными пролифераторами – PPAR-g) в ведении больных с инсулинорезистентностью,ожирением, дислипидемией. Обсуждается доказательная база применения телмисартана как препарата, обладающего плейотропным действием, у больных с артериальной гипертензией и сочетанными заболеваниями (сахарный диабет, ожирение, нарушение функции почек). 

блокаторы рецепторов к ангиотензинутелмисартанартериальная гипертензияангиотензин IIсердечно-сосудистый континуумangiotensin receptor blockerstelmisartanhypertensionangiotensin IIcardiovascular continuumReferencesShalnova S.A., Konradi A.O., Karpov Yu.A., et al. Analysis of mortality from cardiovascular diseases in 12 regions of the Russian Federation participating in the study "Epidemiology of cardiovascular diseases in various regions of Russia". Rossiyskiy Kardiologicheskiy Zhurnal. 2012;5(97):6-11. (In Russ.) [Шальнова С. А., Конради А. О., Карпов Ю. А., и др. Анализ смертности от сердечно-сосудистых заболеваний в 12 регионах Российской Федерации, участвующих в исследовании «Эпидемиология сердечно-сосудистых заболеваний в различных регионах России». Российский Кардиологический Журнал. 2012;5(97):6-11].Shalnova S.A., Konradi A.O., Karpov Yu.A., et al. Analysis of mortality from cardiovascular diseases in 12 regions of the Russian Federation participating in the study "Epidemiology of cardiovascular diseases in various regions of Russia". Rossiyskiy Kardiologicheskiy Zhurnal. 2012;5(97):6-11. (In Russ.) [Шальнова С. А., Конради А. О., Карпов Ю. А., и др. Анализ смертности от сердечно-сосудистых заболеваний в 12 регионах Российской Федерации, участвующих в исследовании «Эпидемиология сердечно-сосудистых заболеваний в различных регионах России». Российский Кардиологический Журнал. 2012;5(97):6-11].Oganov R.G., Maslennikova G.Ya. Demographic trends in the Russian Federation: the contribution of diseases of the circulatory system. Kardiovaskulyarnaya Terapiya i Profilaktika. 2012; 1: 5-10. (In Russ.) [Оганов Р.Г., Масленникова Г.Я. Демографические тенденции в Российской Федерации: вклад болезней системы кровообращения. Кардиоваскулярная Терапия и Профилактика. 2012;1:5-10].Oganov R.G., Maslennikova G.Ya. Demographic trends in the Russian Federation: the contribution of diseases of the circulatory system. Kardiovaskulyarnaya Terapiya i Profilaktika. 2012; 1: 5-10. (In Russ.) [Оганов Р.Г., Масленникова Г.Я. Демографические тенденции в Российской Федерации: вклад болезней системы кровообращения. Кардиоваскулярная Терапия и Профилактика. 2012;1:5-10].Boytsov S.A., Balanova Yu.A., Shalnova S.A., et al. Arterial hypertension among persons aged 25-64 years: prevalence, awareness, treatment and control. Based on the materials of the ESSE study. Kardiovaskulyarnaya Terapiya i Profilaktika. 2014;13(4):4-14. (In Russ.) [Бойцов С.А., Баланова Ю.А., Шально-ва С.А., и др. Артериальная гипертония среди лиц 25-64 лет: распространенность, осведомленность, лечение и контроль. По материалам исследования ЭССЕ. Кардиоваскулярная Терапия и Профилактика. 2014;13(4):4-14].Boytsov S.A., Balanova Yu.A., Shalnova S.A., et al. Arterial hypertension among persons aged 25-64 years: prevalence, awareness, treatment and control. Based on the materials of the ESSE study. Kardiovaskulyarnaya Terapiya i Profilaktika. 2014;13(4):4-14. (In Russ.) [Бойцов С.А., Баланова Ю.А., Шально-ва С.А., и др. Артериальная гипертония среди лиц 25-64 лет: распространенность, осведомленность, лечение и контроль. По материалам исследования ЭССЕ. Кардиоваскулярная Терапия и Профилактика. 2014;13(4):4-14].Boytsov S.A., Yakushin S.S., Martsevich S.Y., et al. Ambulatory-polyclinic register of cardiovascular diseases. REQUAS. Rational Pharmacotherapy in Cardiology. 2013; 9 (1): 4-14. (In Russ.) [Бойцов С.А., Якушин С.С., Марцевич С.Ю., и др. Амбулаторно-поликлинический регистр кардиоваскулярных заболеваний РЕКВАЗА. Рациональная Фармакотерапия в Кардиологии. 2013;9(1):4-14].Boytsov S.A., Yakushin S.S., Martsevich S.Y., et al. Ambulatory-polyclinic register of cardiovascular diseases. REQUAS. Rational Pharmacotherapy in Cardiology. 2013; 9 (1): 4-14. (In Russ.) [Бойцов С.А., Якушин С.С., Марцевич С.Ю., и др. Амбулаторно-поликлинический регистр кардиоваскулярных заболеваний РЕКВАЗА. Рациональная Фармакотерапия в Кардиологии. 2013;9(1):4-14].Dzau V. The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. J Hypertens Suppl. 2005;23(1):S9-17.Dzau V. The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. J Hypertens Suppl. 2005;23(1):S9-17.Podzolkov V.I. Arterial hypertension. Мoscow: Medical information agency; 2016. (In Russ.) [Подзолков В.И. Артериальная гипертензия. М.: Медицинское информационное агентство; 2016].Podzolkov V.I. Arterial hypertension. Мoscow: Medical information agency; 2016. (In Russ.) [Подзолков В.И. Артериальная гипертензия. М.: Медицинское информационное агентство; 2016].DЯsing R. Pharmacological interventions into the renin-angiotensin system with ACE inhibitors and an-giotensin II receptor antagonists: effects beyond blood pressure lowering. Ther Adv Cardiovasc Dis. 2016;10(3):151-61.DЯsing R. Pharmacological interventions into the renin-angiotensin system with ACE inhibitors and an-giotensin II receptor antagonists: effects beyond blood pressure lowering. Ther Adv Cardiovasc Dis. 2016;10(3):151-61.Chow B.S., Allen T.J. Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease. Clin Sci. 2016;130(15):1307-26.Chow B.S., Allen T.J. Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease. Clin Sci. 2016;130(15):1307-26.Oganov R.G., ed. Total cardiovascular risk: from theory to practice. Moscow: GNITSPM; 2007. (In Russ.) [Оганов Р.Г., ред. Суммарный сердечно-сосудистый риск: от теории к практике. М.:ГНИЦПМ;2007].Oganov R.G., ed. Total cardiovascular risk: from theory to practice. Moscow: GNITSPM; 2007. (In Russ.) [Оганов Р.Г., ред. Суммарный сердечно-сосудистый риск: от теории к практике. М.:ГНИЦПМ;2007].James P.A., Oparil S., Carter B.L., et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-20.James P.A., Oparil S., Carter B.L., et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-20.Mancia G., Fagard R., Narkiewicz K., et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159-219.Mancia G., Fagard R., Narkiewicz K., et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159-219.Chazova I.E., Oschepkova E.V., Zhernakova Yu.V. Clinical recommendations. Diagnosis and treatment of arterial hypertension. Kardiologicheskiy Vestnik. 2015;10(1):3-30. (In Russ.) [Чазова И.Е., Ощепкова Е.В., Жернакова Ю.В. Клинические рекомендации. Диагностика и лечение артериальной гипертонии. Кардиологический Вестник. 2015;10(1):3-30].Chazova I.E., Oschepkova E.V., Zhernakova Yu.V. Clinical recommendations. Diagnosis and treatment of arterial hypertension. Kardiologicheskiy Vestnik. 2015;10(1):3-30. (In Russ.) [Чазова И.Е., Ощепкова Е.В., Жернакова Ю.В. Клинические рекомендации. Диагностика и лечение артериальной гипертонии. Кардиологический Вестник. 2015;10(1):3-30].Pals D.T., Denning G.S., Keenan R.E. Historical development of saralasin. Kidney Int Suppl. 1979;(9):S7-10.Pals D.T., Denning G.S., Keenan R.E. Historical development of saralasin. Kidney Int Suppl. 1979;(9):S7-10.Li E.C., Heran B.S., Wright J.M. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2014;(8):CD009096.Li E.C., Heran B.S., Wright J.M. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2014;(8):CD009096.Fournier A., Messerli F., Achard J., Fernandez L. Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials. J Am Coll Cardiol. 2004;43:1343-7.Fournier A., Messerli F., Achard J., Fernandez L. Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials. J Am Coll Cardiol. 2004;43:1343-7.Chrysant S.G. Current status of dual renin angiotensin aldosterone system blockade for the treatment of cardiovascular diseases. Am J Cardiol. 2010;105(6):849-52.Chrysant S.G. Current status of dual renin angiotensin aldosterone system blockade for the treatment of cardiovascular diseases. Am J Cardiol. 2010;105(6):849-52.Abraham H.M., White C.M., White W.B. The comparative efficacy and safety of the angiotensin receptor blockers in the management of hypertension and other cardiovascular diseases. Drug Saf. 2015;38(1):33-54.Abraham H.M., White C.M., White W.B. The comparative efficacy and safety of the angiotensin receptor blockers in the management of hypertension and other cardiovascular diseases. Drug Saf. 2015;38(1):33-54.Dezsi C.A. The Different Therapeutic Choices with ARBs. Which One to Give? When? Why?. Am J Cardiovasc Drugs. 2016;16(4):255-66Dezsi C.A. The Different Therapeutic Choices with ARBs. Which One to Give? When? Why?. Am J Cardiovasc Drugs. 2016;16(4):255-66Podzolkov V.I., Tarzimanova A.I. A new generation of angiotensin receptor blockers. Moscow: Planida; 2013. (In Russ.) [Подзолков В.И., Тарзиманова А.И. Новое поколение блокаторов рецепторов ангиотензина. М.: Планида; 2013].Podzolkov V.I., Tarzimanova A.I. A new generation of angiotensin receptor blockers. Moscow: Planida; 2013. (In Russ.) [Подзолков В.И., Тарзиманова А.И. Новое поколение блокаторов рецепторов ангиотензина. М.: Планида; 2013].Sharpe M., Jarvis B., Goa K.L. Telmisartan: a review of its use in hypertension. Drugs 2001;61:1501-29.Sharpe M., Jarvis B., Goa K.L. Telmisartan: a review of its use in hypertension. Drugs 2001;61:1501-29.Bakris G. Comparison of telmisartan vs. valsartan in the treatment of mild to moderate hypertension using ambulatory blood pressure monitoring. J Clin Hypertension. 2002; 4(4):26-31.Bakris G. Comparison of telmisartan vs. valsartan in the treatment of mild to moderate hypertension using ambulatory blood pressure monitoring. J Clin Hypertension. 2002; 4(4):26-31.The ONTARGET investigators. Telmisartan, ramipril or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-59.The ONTARGET investigators. Telmisartan, ramipril or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-59.The TRANSCEND investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372:1174-83The TRANSCEND investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372:1174-83Barnett A.H., Bain S.C., Bouter P., et al. Diabetics exposed to telmisartan and enalapril study group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351(19):1952-61.Barnett A.H., Bain S.C., Bouter P., et al. Diabetics exposed to telmisartan and enalapril study group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351(19):1952-61.Galle J., Schwedhelm E., Pinnetti S., et al. VIVALDI investigators. Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy. Nephrol Dial Transplant. 2008;23(10):3174-83.Galle J., Schwedhelm E., Pinnetti S., et al. VIVALDI investigators. Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy. Nephrol Dial Transplant. 2008;23(10):3174-83.Prasad B., Ravi N., Asma K., et al. Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study. Vasc Health Risk Manag. 2009;5:129-40.Prasad B., Ravi N., Asma K., et al. Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study. Vasc Health Risk Manag. 2009;5:129-40.Makino H., Haneda M., Babazono T., et al. The telmisartan renoprotective study from incipient nephropathy to overt nephropathy - rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, investigation on type 2 diabetic nephropathy (INNOVATION) Study. J Int Med Res. 2005;33:677-86.Makino H., Haneda M., Babazono T., et al. The telmisartan renoprotective study from incipient nephropathy to overt nephropathy - rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, investigation on type 2 diabetic nephropathy (INNOVATION) Study. J Int Med Res. 2005;33:677-86.Williams B., Lacourciere Y., Schumacher H., et al. Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRIS-MA I and II randomized trials. J Hum Hypertens. 2009;23(9):610-9.Williams B., Lacourciere Y., Schumacher H., et al. Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRIS-MA I and II randomized trials. J Hum Hypertens. 2009;23(9):610-9.Schmieder R.E., Delles C., Mimran A. et al. Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes. Diabetes Care 2007;30:1351-6.Schmieder R.E., Delles C., Mimran A. et al. Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes. Diabetes Care 2007;30:1351-6.Takagi H., Yamamoto H., Iwata K., et al. Effects of telmisartan on proteinuria or albuminuria: a meta-analysis of randomized trials. Int J Cardiol. 2013;167(4):1443-9.Takagi H., Yamamoto H., Iwata K., et al. Effects of telmisartan on proteinuria or albuminuria: a meta-analysis of randomized trials. Int J Cardiol. 2013;167(4):1443-9.Zhernakova Yu.V., Chazova I.E. Possibilities of a new receptor blocker for angiotensin II of azilsartan me-doxomil in the treatment of arterial hypertension in patients with metabolic disorders. Sistemnye Gipertenzii. 2014; 4 (11): 58-61. (In Russ.) [Жернакова Ю.В., Чазова И.Е. Возможности нового блокатора рецепторов к ангиотензину II азилсартана медоксомила в лечении артериальной гипертонии у пациентов с метаболическими нарушениями. Системные Гипертензии. 2014;4(11):58-61].Zhernakova Yu.V., Chazova I.E. Possibilities of a new receptor blocker for angiotensin II of azilsartan me-doxomil in the treatment of arterial hypertension in patients with metabolic disorders. Sistemnye Gipertenzii. 2014; 4 (11): 58-61. (In Russ.) [Жернакова Ю.В., Чазова И.Е. Возможности нового блокатора рецепторов к ангиотензину II азилсартана медоксомила в лечении артериальной гипертонии у пациентов с метаболическими нарушениями. Системные Гипертензии. 2014;4(11):58-61].Barutcuoglu B., Parildar Z., Mutaf M.I. et al. Effect of telmisartan on vascular endothelium in hypertensive and type 2 diabetic hypertensive patients . Turk J Med Sci. 2010;40(2):239-48.Barutcuoglu B., Parildar Z., Mutaf M.I. et al. Effect of telmisartan on vascular endothelium in hypertensive and type 2 diabetic hypertensive patients . Turk J Med Sci. 2010;40(2):239-48.Suksomboon N., Poolsup N., Prasit T. Systematic review of the effect of telmisartan on insulin sensitivity in hypertensive patients with insulin resistance or diabetes. J Clin Pharm Ther. 2012;37(3):319-27.Suksomboon N., Poolsup N., Prasit T. Systematic review of the effect of telmisartan on insulin sensitivity in hypertensive patients with insulin resistance or diabetes. J Clin Pharm Ther. 2012;37(3):319-27.Takagi H., Niwa M., Mizuno Y., et al. Telmisartan as a metabolic sartan: the first meta-analysis of randomized controlled trials in metabolic syndrome. J Am Soc Hypertens. 2013;7(3):229-35.Takagi H., Niwa M., Mizuno Y., et al. Telmisartan as a metabolic sartan: the first meta-analysis of randomized controlled trials in metabolic syndrome. J Am Soc Hypertens. 2013;7(3):229-35.Huang G.Z., Tang Y.H., Wang B.Y., et al. Effects of telmisartan on insulin resistance and visceral fat distribution in Chinese hypertensive patients with obesity. Saudi Med J. 2011;32(10):1017-21.Huang G.Z., Tang Y.H., Wang B.Y., et al. Effects of telmisartan on insulin resistance and visceral fat distribution in Chinese hypertensive patients with obesity. Saudi Med J. 2011;32(10):1017-21.Murakami K., Wada J., Ogawa D., et al. The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO). Diab Vasc Dis Res. 2013;10(1):93-6Murakami K., Wada J., Ogawa D., et al. The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO). Diab Vasc Dis Res. 2013;10(1):93-6

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