Regression of the target organ damage under fixed dose combination perindopril/amlodipin in hypertensive patients with and without ischemic heart disease

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G. D. Radchenko
L. O. Mushtenko
Yu. M. Sirenko


The aim – to assess factors associated with regression of target organ damage under therapy with fixed dose combination (FDC) of perindopril and amlodipine in patients with arterial hypertension, depending on presence of the ischemic heart disease (according to the EPHES study results analysis).
Material and methods. The analysis included data of 60 patients (aged > 30 years) with arterial hypertension:
1st group – 30 patients without ischemic heart disease (IHD), 2nd group – 30 patients with IHD. All patients were administered FDC perindopril/amlodipine in daily baseline dose 5/5 mg with up-titration to 10/10 mg every two weeks. If target blood pressure (BP) was not achieved (> 140/90 mm Hg) after 6 weeks, the indapamide 1.5 mg was added. All patients were done: body mass index measurements, office and ambulatory BP measurements, pulse wave velocity (PWV) and central SBP evaluation, augmentation index adjusted to heart rate 75 (AIx75) evaluation, biochemical blood analysis, ECG, EchoCG with Doppler, ankle-brachial index, intima-media thickness (IMT). The follow-up period was
12 months.
Results. Effective BP decreasing treatment based on FDC led to significant target organ damage regression – improving arterial stiffness and left ventricular diastolic function, decreasing of urine albumin level, left ventricular hypertrophy and left atrium size. Lowering of aorta PWV was less in patients without IHD than in patients with IHD – by 2.5±0.2 vs 4.4±0.5 m/s (Р<0.005). Despite equal decreasing of left ventricular mass indices in both groups, improving of diastolic function (increasing of E/A and diminishing Е/Е′) was more in patients with IHD – 64.4 and 54.1 % vs 39.8 and 23.2 % (Р<0.05 for both respectively). IMTmax decreased significantly only in patients with IHD.
Conclusions. The assessed common and different factors associated with target organ damage regression in patients with and without IHD might help in choice of antihypertensive therapy and management of patients with arterial hypertension.

Article Details


arterial hypertension, ischemic heart disease, target organ damage regression, fixed combination perindopril / amlodipine


Компендіум. Лікарські засоби / За ред. В.М. Коваленка та А.П. Вікторова.– К.: Моріон, 2010.– С. 219.

Методичні рекомендації Асоціації кардіологів України. Дисліпідемії: діагностика, профілактика та лікування.– К., 2011.– 49 с.

Радченко Г., Муштенко Л., Торбас О. та ін. Оцінка впливу фіксованої комбінації периндоприл/амлодипін на ураження органів-мішеней у пацієнтів з артеріальною гіпертензією (первинні результати дослідження EPHES) // Артеріальна гіпертензія.– 2015.– № 4.– С. 27–41.

Радченко Г., Муштенко Л., Торбас О. та ін. Оцінка впливу фіксованої комбінації периндоприл/амлодипін на ураження органів-мішеней у пацієнтів з артеріальною гіпертензією та ішемічною хворобою серця (результати дослідження EPHES // Артеріальна гіпертензія.– 2016.– № 2.– С. 77–92.

Радченко Г., Муштенко Л., Торбас О. та ін. Порівняння впливу фіксованої комбінації периндоприл/амлодипін на ураження органів-мішеней у пацієнтів з артеріальною гіпертензією з та без ішемічної хвороби серця (результати дослідження EPHES) // Артеріальна гіпертензія.– 2016.– № 5.– С. 11–25.

Радченко Г.Д., Торбас О.О., Сіренко Ю.М. Клінічне значення тиску, виміряного різними способами, у пацієнтів з артеріальною гіпертензією // Артериальная гипертензия.– 2014.– № 5.– С. 41–48.

Торбас О.О., Радченко Г.Д Порівняння значення офісного, середньодобового та центрального артеріального тиску у формуванні ураження органів-мішеней // Артериальная гипертензия.– 2014.– № 3.– С. 49–53.

Agoşton-Coldea L., Mocan T., Bobar C. Arterial stiffness and left ventricular diastolic function in the patients with hypertension // Rom. J. Intern. Med.– 2008.– Vol. 46 (4).– P. 313–321.

Anversa P., Hiler B., Ricci R. et al. Myocyte cell loss and myocyte hypertrophy in the aging rat heart // J. Am. Coll. Cardiol.– 1986.– Vol. 8.– P. 1441–1448.

Anversa P., Palackal T., Sonnenblick E.H. et al. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart // Circ. Res.– 1990.– Vol. 67.– P. 871–885.

Balkestein E.J., Staessen J.A., Wang J.G. et al. Carotid and femoral artery stiffness in relation to three candidate genes in a white population.– Hypertension.– 2001.– Vol. 38.– P. 1190–1197.

Bouchi R., Babazono T., Mugishima M. et al. Arterial Stiffness Is Associated With Incident Albuminuria and Decreased Glomerular Filtration Rate in Type 2 Diabetic Patients // Diabetes Care.– 2011.– Vol. 34.– Р. 2570–2575.

Cheng S., Fernandes V.R.S., Bluemke D.A. et al. Age-Related Left Ventricular Remodeling and Associated Risk for Cardiovascular Outcomes. The Multi-Ethnic Study of Athero­sclerosis // Circulation: Cardiovascular Imaging. 2009.– Vol. 2.– P. 191–198. CIRCIMAGING.108.819938

Cuspidi C., Meani S., Sala C. et al. Age related prevalence of severe left ventricular hypertrophy in essential

hypertension: echocardiographic findings from the ETODH study // Blood press.– 2012.– Vol. 21(3).– P. 139–145.

doi: 10.3109/08037051.2012.668662.

Diaz A., Galli C., Tringler M., Ramirez A., Fischer E. Reference Values of Pulse Wave Velocity in Healthy People from an Urban and Rural Argentinean Population // Intern. J. Hypertension.– 2014.– Vol. 2014.– P. 1–7.

Dong I Shin, Ki-Bae Seung, Hye Eun Yoon, Byung-Hee Hwang et al. Microalbuminuria is Independently Associated with Arterial Stiffness and Vascular Inflammation but not with Carotid Intima-Media Thickness in Patients with Newly Diagnosed Type 2 Diabetes or Essential Hypertension // J. Korean Med. Sci.– 2013.– Vol. 28.– P. 252–260. doi: 10.3346/jkms.2013.28.2.252

Foppa M., Duncan B., Rohde L. Echocardiography-based left ventricular mass estimation. How should we define hypertrophy? // Cardiovasc Ultrasound. 2005.– Vol. 3.– P. 17. doi:10.1186/1476-7120-3-17

Gosse Ph., Sheridan D., Zannad F. et al. on behalf of the LIVE investigators. Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study // J. Hypertension.– 2000.– Vol. 18.– P. 1465–1475.

Jaroch J., Łoboz Grudzień K., Bociąga Z. et al. The relationship of carotid arterial stiffness to left ventricular diastolic dysfunction in untreated hypertension // Kardiol. Pol.– 2012.– Vol. 70 (3).– P. 223–231.

Kim B.J., Lee H.A., Kim N.H. et al. The association of albuminuria, arterial stiffness, and blood pressure status in nondiabetic, nonhypertensive individuals // J. Hypertens.– 2011.– Vol. 29 (11).– P. 2091–2098. doi: 10.1097/HJH.0b013e32834b5627

Levey A., Stevens L., Schmid C. et al. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate // Ann. Intern. Med.– 2009.– Vol. 150 (9).– P. 604–612.

Lewis E.J., Hunsicker L.G., Bain R.P. et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy // N. Engl. J. Med.– 1993.– Vol. 329.– P. 1456–1462. doi: 10.1056/NEJM199311113292004

London G.M., Pannier B., Guerin A.P. et al. Cardiac hyper­­trophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: comparative effects of ACE inhibition and calcium channel blockade // Circulation.– 1994.– Vol. 90.– Р. 2786–2796.

Mahmud A., Feely J. Reduction in arterial stiffness with angiotensin II antagonist is comparable with and additive to ACE inhibition // Am. J. Hypertens.– 2002.– Vol. 15.– P. 321–325.

McEniery C., Yasmin, Hall I. et al. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: The Anglo-Cardiff Collaborative Trial (ACCT) // J. Amer. Coll. Cardiology.– 2005.– Vol. 46.– P. 1753–1760.

McEniery C., Yasmin, McDonnell B. et al. on behalf of the ACCT Investigators. Central pressure: variability and impact of cardiovascular risk factors. The anglo-cardiff collaborative trial II // Hypertension.– 2008.– Vol. 51.– P. 1476–1482. doi: 10.1161/HYPERTENSIONAHA.107.105445.

Mogensen C.E., Viberti G., Halimi S. et al. Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER // Hypertension.– 2003.– Vol. 41 (5).– P. 1063–1071.

Olivetti G., Giordano G., Corradi D. et al. Gender differences and aging: effects on the human heart // J. Am. Coll. Cardiol.– 1995.– 26.– P. 1068–1079.

Olivetti G., Melissari M., Capasso J.M., Anversa P. Cardio­­myopathy of the aging human heart: myocyte loss and reactive cellular hypertrophy // Circ. Res.– 1991.– Vol. 68.– P. 1560–1568.

Ostergren J., Poulter N.R., Sever P.S. et al.; ASCOT investigators. The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes // J. Hypertens.– 2008.– Vol. 26 (11).– P. 2103–2111. doi: 10.1097/HJH.0b013e328310e0d9

Pannier B.M., Guerin A.P., Marchais S.J., London G.M. Different aortic reflection wave responses following long-term angiotensin-converting enzyme inhibition and beta-blocker in essential hypertension // Clin. Exp. Pharmacol. Physiol.– 2001.– Vol. 28.– P. 1074–1077. doi: 10.1046/j.1440-1681.2001.03570.x

Rogers W., Hu Y., Coast D. et al. Age-associated changes in regional aortic pulse wave velocity// J. Amer. Coll. Cardiology.– 2001.– Vol. 38.– P. 1123–1129. doi: 10.1016/S0735-1097(01)01504-2

Roman M., Devereux R., Kizer J. et al. High Central Pulse Pressure Is Independently Associated With Adverse Cardiovascular Outcome The Strong Heart Study // J. Amer. Coll. Cardiol. 2009.– Vol. 54.– P. 1730–1733. doi: 10.1016/j.jacc.2009.05.070.

Safar M. Macro- and microcirculation in hypertension.– Lippincott Williams & Wilkins: London, 2005.– 151 p.

Satchell S., Tooke J. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? // Diabetologia.– 2008.– Vol. 51 (5).– P. 714–725. doi: 10.1007/s00125-008-0961-8

Simonson E., Nakagawa K. Effect of age on pulse wave velocity and «Aortic Ejection Time» in Healthy men and in men with coronary artery disease // Circulation.– 1960.– Vol. XXII.– P. 126–129. doi: 10.1161/01.CIR.22.1.126

Stein J., Korcarz C., Hurst R. et al. American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography carotid intima-media thickness task force endorsed by the society of vascular medicine // J. Am. Society Echoc.– 2008.– Vol. 21 (2).– P. 93–111. doi: 10.1016/j.echo.2007.11.011.

The CAFE Investigators, for the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Investigators CAFE Steering Committee and Writing Committee. Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes Principal Results of the Conduit Artery Function Evaluation (CAFE) Study // Circulation.– 2006.– Vol. 113.– P. 1213–1225. doi: 10.1161/CIRCULATIONAHA.105.595496

Tomiyama H., Kimura Y., Sakuma Y. et al. Effects of an ACE inhibitor and a calcium channel blocker on cardiovascular autonomic nervous system and carotid distensibility in patients with mild to moderate hypertension // Am. J. Hypertens. –1998.–Vol. 11.– P. 682–689 doi:

Van den Meiracker A.H., Mattace-Raso F. US. Large artery stiffness and microalbuminuria: a causal relationship? // J. Hypertension.– 2009.– Vol. 27.– P. 1355–1357.,

Viberti G., Wheeldon N.M. MicroAlbuminuria Reduction With VALsartan (MARVAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect // Circulation.– 2002.– Vol. 106 (6).– P. 672–678.

White W. Blood pressure monitoring in Cardiovascular Medicine and Therapeutics.– N. Jersy: Humana Press, 2001.– P. 308.

ESH/ESC Guidelines for the management of arterial hypertension TheTask Force for the management ofarterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // J. Hypertension.– 2013.– Vol. 31.– P. 1281–1357. doi: 10.1097/

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