cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-1332Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESИзучение эффективности терапии ингибитором ангиотензин-превращающего фермента рамиприлом и его комбинации с гидрохлортиазидом у пациентов с артериальной гипертонией и избыточной массой тела: исследование ХАРИЗМАEffectiveness of ACE inhibitor ramipril and its combination with hydrochlorothiazide in patients with arterial hypertension and overweight: CHARISMA StudyКолосИ. П.KolosI. P.docsn173@yandex.ruМартынюкТ. В.MartynyukT. V.docsn173@yandex.ruСафарянА. С.SafaryanA. S.docsn173@yandex.ruНебиеридзеД. В.NebieridzeD. V.docsn173@yandex.ruЧазоваИ. Е.ChazovaI. E.docsn173@yandex.ruФГУ Российский кардиологический научно-производственный комплекс РосмедтехнологииRussian Cardiology Scientific and Clinical Complex, Federal Agency on High Medical TechnologiesФГУ Государственный научно-исследовательский центр профилактической медицины Росмедтехнологии, г. МоскваState Research Center for Preventive Medicine, Federal Agency on High Medical Technologies. Moscow200820042008726571Copyright © Колос И.П., Мартынюк Т.В., Сафарян А.С., Небиеридзе Д.В., Чазова И.Е., 20082008Колос И.П., Мартынюк Т.В., Сафарян А.С., Небиеридзе Д.В., Чазова И.Е.Kolos I.P., Martynyuk T.V., Safaryan A.S., Nebieridze D.V., Chazova I.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/1332Цель

Цель. Оценить эффективность и безопасность рамиприла, назначаемого в разное время суток, у пациентов с мягкой/умеренной артериальной гипертонией (АГ) и избыточной массой тела (МТ).

Материал и методы

Материал и методы. Пациенты были рандомизированы на две группы: 29 (I группа) пациентов с АГ в течение 4 недель принимали рамиприл (Хартил®, ЭГИС ОАО, Венгрия) в дозе 5 мг/сут. в утренние часы (8:00-10:00), 39 (II группа) - рамиприл 5 мг/сут. в вечерние часы (21:00-23:00). Спустя 4 недели пациентам обеих групп, не достигшим целевого уровня АД (<140/90 мм рт.ст.), дозу рамиприла увеличили до 10 мг/сут. Через 8 недель лечения при недостижении целевого АД больным обеих групп добавили гидрохлортиазид в дозе 12,5 мг/сут. Общая продолжительность исследования - 16 недель.

Результаты

Результаты. Через 16 недель лечения уровень АД между группами достоверно не отличался. По данным офисного измерения САД и ДАД через 16 недель терапии рамиприлом достоверно снизились в I и II группах (р<0,05 и р<0,05 соответственно). По данным суточного мониторирования АД через 8 и 16 недель средние САД и ДАД достоверно снизились при лечении рамиприлом в I и II группах. Различия по уровню АД в дневные и ночные часы между группами не достигали достоверных значений.

Заключение

Заключение. Рамиприл эффективно и безопасно снижает АД, уменьшает уровень микроальбуминурии у больных AT I-II степеней с избыточной МТ вне зависимости от времени однократного приема препарата.

Aim

Aim. To investigate effectiveness and safety of ramipril therapy, with varying administration time, in patients with mild to moderate arterial hypertension (AH) and overweight (OW).

Material and methods

Material and methods. The patients were randomized into two groups: Group I (n=29) received ramipril (Hartil®, FGIS, Hungary) in the morning (5 mg/d, at 8-10 am) for 4 weeks; Group II(n=39) received the medication in the evening (5 mg/d, 9-11 pm). Four weeks later, in all patients not achieved target blood pressure (BP) levels (<140/90 mm Hg), ramipril dose was increased up to 10 mg/d. If target BP levels were not achieved after 8 weeks, hydrochlorothiazide (12,5 mg/d) was added. The total length of the study was 16 weeks.

Results

Results. After 16 weeks of the treatment, BP levels were similar in both groups. According to office BP measurement results, systolic and diastolic BP (SBP, DBP) levels were significantly reduced in Groups I and II (p<0,05). According to 24-hour BP monitoring data, obtained after 8 and 16 weeks, mean SBP and DBP levels significantly decreased in Weeks 8 and 16 for Groups I and II, respectively. Day- and nighttime BP difference was similar in both groups.

Conclusion

Conclusion. Regardless of its administration time, ramipril effectively and safely reduced BP and microalbuminuria levels in patients with Stage I-II AH and OW.

артериальная гипертензияизбыточная масса теларамиприлarterial hypertensionoverweightramiprilReferencesMancia G., Bombelli M., Corrao G. et al. Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis. Hypertension 2007; 49: 40-7.Mancia G., Bombelli M., Corrao G. et al. Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis. Hypertension 2007; 49: 40-7.Lakka H.M., Laaksonen D.E., Lakka Т.А. et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709-16.Lakka H.M., Laaksonen D.E., Lakka Т.А. et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709-16.Girman C.J., Rhodes T., Mercuri M. et al, 4S Group and the AFCAPS/TexCAPS Research Group. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol 2004; 93: 136-41.Girman C.J., Rhodes T., Mercuri M. et al, 4S Group and the AFCAPS/TexCAPS Research Group. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol 2004; 93: 136-41.Dekker J.M., Girman C., Rhodes T. et al. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation 2005; 112: 666-73.Dekker J.M., Girman C., Rhodes T. et al. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation 2005; 112: 666-73.Resnick H.E., Jones K., Ruotolo G. et al. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease in nondiabetic American Indians: the Strong Heart Study. Diabetes Care 2003; 26: 861-7.Resnick H.E., Jones K., Ruotolo G. et al. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease in nondiabetic American Indians: the Strong Heart Study. Diabetes Care 2003; 26: 861-7.Schmidt M.I., Duncan B.B., Bang H. et al. Identifying individuals at high risk for diabetes: The Atherosclerosis Risk in Communities study. Diabetes Care 2005; 28: 2013-8.Schmidt M.I., Duncan B.B., Bang H. et al. Identifying individuals at high risk for diabetes: The Atherosclerosis Risk in Communities study. Diabetes Care 2005; 28: 2013-8.Vasan R.S., Beiser A., Seshadri S. et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA 2002; 287: 1003-10.Vasan R.S., Beiser A., Seshadri S. et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA 2002; 287: 1003-10.Vasan R.S., Larson M.G., Leip E.P. et al. Assessment of frequency of progression to hypertension in non-hypertensive participants in the FraminghamHeart Study: a cohort study. Lancet 2001; 358: 1682-6.Vasan R.S., Larson M.G., Leip E.P. et al. Assessment of frequency of progression to hypertension in non-hypertensive participants in the FraminghamHeart Study: a cohort study. Lancet 2001; 358: 1682-6.Vasan R.S., Larson M.G., Leip E.P. et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001; 345: 1291-7.Vasan R.S., Larson M.G., Leip E.P. et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001; 345: 1291-7.Julius S., Nesbitt S.D., Egan B.M. et al., Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006; 354: 1685-97.Julius S., Nesbitt S.D., Egan B.M. et al., Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006; 354: 1685-97.Mule' G., Nardi E., Cottone S. et al. Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med 2005; 257: 503-13.Mule' G., Nardi E., Cottone S. et al. Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med 2005; 257: 503-13.Leoncini G., Ratto E., Viazzi F. et al. Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med 2005; 257: 454-60.Leoncini G., Ratto E., Viazzi F. et al. Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med 2005; 257: 454-60.Cuspidi C., Meani S., Fusi V. et al. Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens 2004; 22: 1991-8.Cuspidi C., Meani S., Fusi V. et al. Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens 2004; 22: 1991-8.Schillaci G., Pirro M., Vaudo G. et al. Metabolic syndrome is associated with aortic stiffness in untreated essential Hypertension. Hypertension 2005; 45: 1978-82.Schillaci G., Pirro M., Vaudo G. et al. Metabolic syndrome is associated with aortic stiffness in untreated essential Hypertension. Hypertension 2005; 45: 1978-82.de Simone G., Palmieri V., Bella J.N. et al. Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study. J Hypertens 2002; 20: 323-31.de Simone G., Palmieri V., Bella J.N. et al. Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study. J Hypertens 2002; 20: 323-31.Schillaci G., Pirro M., Pucci G. et al. Different impact of the metabolic syndrome on left ventricular structure and function in hypertensive men and women. Hypertension 2006; 47: 881-6.Schillaci G., Pirro M., Pucci G. et al. Different impact of the metabolic syndrome on left ventricular structure and function in hypertensive men and women. Hypertension 2006; 47: 881-6.Cuspidi C., Meani S., Fusi V. et al. Prevalence and correlates of left atrial enlargement in essential hypertension: role of ventricular geometry and the metabolic syndrome: the Evaluation of Target Organ Damage in Hypertension study. J Hypertens 2005; 23: 875-82.Cuspidi C., Meani S., Fusi V. et al. Prevalence and correlates of left atrial enlargement in essential hypertension: role of ventricular geometry and the metabolic syndrome: the Evaluation of Target Organ Damage in Hypertension study. J Hypertens 2005; 23: 875-82.Kawamoto R., Tomita H., Oka Y. et al. Metabolic syndrome amplifies the LDL-cholesterol associated increases in carotid atherosclerosis. J Intern Med 2005; 44: 1232-8.Kawamoto R., Tomita H., Oka Y. et al. Metabolic syndrome amplifies the LDL-cholesterol associated increases in carotid atherosclerosis. J Intern Med 2005; 44: 1232-8.Cuspidi C., Meani S., Valerio C. et al. Ambulatory blood pressure, target organ damage and left atrial size in never-treated essential hypertensive individuals. J Hypertens 2005; 23: 1589-95.Cuspidi C., Meani S., Valerio C. et al. Ambulatory blood pressure, target organ damage and left atrial size in never-treated essential hypertensive individuals. J Hypertens 2005; 23: 1589-95.Guidelines Committee. 2007 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension 2007; 25: 1105-87.Guidelines Committee. 2007 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension 2007; 25: 1105-87.Mancia G., Grassi G., Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens 2006; 24: 3-10.Mancia G., Grassi G., Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens 2006; 24: 3-10.Opie L.H., Schall R. Old antihypertensives and new diabetes. J Hypertens 2004; 22: 1453-8.Opie L.H., Schall R. Old antihypertensives and new diabetes. J Hypertens 2004; 22: 1453-8.Elliott W.J., Meyer P.M. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201-7.Elliott W.J., Meyer P.M. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201-7.Abuissa H., Jones P.G., Marso S.P., O'Keefe J.H. Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. JACC 2005; 46: 821-6.Abuissa H., Jones P.G., Marso S.P., O'Keefe J.H. Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. JACC 2005; 46: 821-6.Rocchini A.P. Obesity hypertension, salt sensitivity and insulin resistance. Nutr Metab Cardiovasc Dis 2000; 10: 287-94.Rocchini A.P. Obesity hypertension, salt sensitivity and insulin resistance. Nutr Metab Cardiovasc Dis 2000; 10: 287-94.The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145-53.The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145-53.Jackie Bosch. Effect of Ramipril on the Incidence of Diabetes. N Engl J Med 2006; 355: 1551-62.Jackie Bosch. Effect of Ramipril on the Incidence of Diabetes. N Engl J Med 2006; 355: 1551-62.Ibsen H., Olsen M.H., Wachtell K. et al. Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study. Diabetes Care 2006; 29: 595-600.Ibsen H., Olsen M.H., Wachtell K. et al. Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study. Diabetes Care 2006; 29: 595-600.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; 106: 672-8.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; 106: 672-8.Vogt L., Navis G., Koster J. et al., on behalf of the Angiotensin II Receptor Antagonist Telmisartan Micardis in Isolated Systolic Hypertension (ARAMIS) Study Group. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23: 2055-61.Vogt L., Navis G., Koster J. et al., on behalf of the Angiotensin II Receptor Antagonist Telmisartan Micardis in Isolated Systolic Hypertension (ARAMIS) Study Group. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23: 2055-61.White W.B., Duprez D., St Hillaire R. et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic Hypertension. Hypertension 2003; 41: 1021-6.White W.B., Duprez D., St Hillaire R. et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic Hypertension. Hypertension 2003; 41: 1021-6.Ruggenenti P., Fassi A., Ilieva A.P. et al., Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J MedRuggenenti P., Fassi A., Ilieva A.P. et al., Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med

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