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Регресс субклинического поражения органов-мишеней у больных гипертонической болезнью на фоне различных подходов к назначению комбинированной антигипертензивной терапии
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Аннотация
Цель: оценить динамику показателей, характеризующих субклиническое поражение органов-мишеней, на фоне различных подходов к назначению комбинированной антигипертензивной терапии (АГТ) блокаторами ренин-ангиотензин-альдостероновой системы у больных гипертонической болезнью (ГБ).
Материалы и методы: обследованы 60 больных ГБ, имеющих субклиническое поражение сердца, по данным состояния коллагенового матрикса миокарда левого желудочка (TIMP-1, CTP-1) без гипертрофии левого желудочка, артерий по показателям объемной сфигмоплетизмографии, почек по уровню микроальбуминурии (МАУ) и скорости клубочковой фильтрации (СКФ) по формуле MDRD. Больные были разделены на 2 равные группы в зависимости от выбора АГТ. Пациенты 1-й группы получали фиксированную комбинацию эпросартана мезилата и гидрохлоротиазида независимо от уровня артериального давления (АД) и сердечно-сосудистого риска (ССР). Во 2-й группе АГТ назначали в зависимости от уровня АД и ССР: монотерапия эналаприлом и нефиксированная комбинация его с гидрохлоротиазидом. Длительность терапии составила 6 мес.
Результаты: достоверных различий между группами в достижении целевого уровня АД не выявлено. Регресс субклинического поражения органов-мишеней в 1-й группе больных был более выражен, чем во 2-й группе: по динамике показателей TIMP-1 (p=0,011), скорости пульсовой волны в каротидно-феморальном сегменте (p=0,021), в плече-лодыжечном сегменте (p=0,042), в аорте (p=0,036) независимо от уровня АД (индекс CAVI1, p=0,005), МАУ (p<0,001) и СКФ (p<0,001).
Заключение: регресс субклинического поражения органов-мишеней у больных ГБ зависит не столько от достижения целевого уровня АД, сколько от выбора стратегии АГТ в дебюте лечения.
Ключевые слова: регресс субклинического поражения органов-мишеней, гипертоническая болезнь, комбинированная антигипертензивная терапия.
Материалы и методы: обследованы 60 больных ГБ, имеющих субклиническое поражение сердца, по данным состояния коллагенового матрикса миокарда левого желудочка (TIMP-1, CTP-1) без гипертрофии левого желудочка, артерий по показателям объемной сфигмоплетизмографии, почек по уровню микроальбуминурии (МАУ) и скорости клубочковой фильтрации (СКФ) по формуле MDRD. Больные были разделены на 2 равные группы в зависимости от выбора АГТ. Пациенты 1-й группы получали фиксированную комбинацию эпросартана мезилата и гидрохлоротиазида независимо от уровня артериального давления (АД) и сердечно-сосудистого риска (ССР). Во 2-й группе АГТ назначали в зависимости от уровня АД и ССР: монотерапия эналаприлом и нефиксированная комбинация его с гидрохлоротиазидом. Длительность терапии составила 6 мес.
Результаты: достоверных различий между группами в достижении целевого уровня АД не выявлено. Регресс субклинического поражения органов-мишеней в 1-й группе больных был более выражен, чем во 2-й группе: по динамике показателей TIMP-1 (p=0,011), скорости пульсовой волны в каротидно-феморальном сегменте (p=0,021), в плече-лодыжечном сегменте (p=0,042), в аорте (p=0,036) независимо от уровня АД (индекс CAVI1, p=0,005), МАУ (p<0,001) и СКФ (p<0,001).
Заключение: регресс субклинического поражения органов-мишеней у больных ГБ зависит не столько от достижения целевого уровня АД, сколько от выбора стратегии АГТ в дебюте лечения.
Ключевые слова: регресс субклинического поражения органов-мишеней, гипертоническая болезнь, комбинированная антигипертензивная терапия.
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Aim: to evaluate the time course of changes in the parameters characterizing subclinical target organ damage during different approaches to combination antihypertensive therapy (CAHT) with renin-angiotensin-aldosterone system blockers in hypertensive patients.
Subjects and methods. Examinations were made in 60 hypertensive patients with subclinical damage to the heart according to the data on left ventricular collagen matrix (TIMP-1, CTP-1) without left ventricular hypertrophy, arteries from volume sphygmoplethysmographic findings, kidneys from urinary microalbumin (UMA) levels and glomerular filtration rate (GFR), by employing the Modification Diet in Renal Disease formula. The patients were divided into two matched groups according to the choice of antihypertensive therapy (AHT). Group 1 patients received a fixed-dose combination of eprosartan mesylate and hydrochlorothiazide regardless of blood pressure (BP) levels and a cardiovascular risk (CVR). In Group 2, AHT was used depending on the level of BP and CVR: monotherapy with enalapril and its non-fixed dose combination with hydrochlorothiazide. The duration of the therapy was 6 months.
Results. No significant differences were found between the groups in attaining BP goals. In Group 1, regression of subclinical target organ damage was more pronounced than that Group 2 in terms of TIMP-1 levels (p=0,011), pulse wave velocity in the carotid-femoral (p=0,021) and brachiomalleolar (p=0,042) segments, and aorta (p=0,036) irrespective of BP (CAVI1, p=0,005) and UMA levels (p<0,001), and GFR (p<0,001).
Conclusion. Regression of subclinical target organ damage in hypertensive patients depends on the choice of a strategy of AHT at the time of its start rather than on the attainment of BP goals.
Key words: regression of subclinical target organ damage, hypertensive disease, combination antihypertensive therapy.
Полный текст
Список литературы
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31. Martin DE, DeCherney GS, Ilson BE et al. Eprosartan, an angiotensin II receptor antagonist, does not affect the pharmacodynamics of glyburide in patients with type II diabetes mellitus. J Clin Pharmacol 1997; 37 (2): 155–9.
32. Ilson BE, Boike SC, Martin DE et al. A dose-response study to assess the renal hemodynamic, vascular, and hormonal effects of eprosartan, an angiotensin II AT1-receptor antagonist, in sodium-replete healthy men. Clin Pharmacol Ther 1998; 63 (4): 471–81.
2. Coutinho T, Turner ST, Kullo I. Aortic pulse wave velocity is associated with measures of subclinical target organ damage. JACC Cardiovasc Imaging 2011; 4 (7): 754–61.
3. García-García A, Gómez-Marcos MA, Recio-Rodriguez JI et al. Relationship between ambulatory arterial stiffness index and subclinical target organ damage in hypertensive patients. J Hypertens Res 2011; 34 (2): 180–6.
4. Matsumoto C, Tomiyama H, Yamada J. Brachial-ankle pulse wave velocity as a marker of subclinical organ damage in middle-aged patients with hypertension. J Cardiol 2008; 51 (3): 163–70.
5. Triantafyllidi H, Tzortzis S, Lekakis J et al. Association of target organ damage with three arterial stiffness indexes according to blood pressure dipping status in untreated hypertensive patients. Am J Hypertens 2010; 23 (12): 1265–72.
6. Castro MM, Tanus-Santos JE, Gerlach RF Matrix metalloproteinases: Targets for doxycycline to prevent the vascular alterations of hypertension. Pharmacol Res 2011; 64 (6): 567–72.
7. Jones CB, Sane DC, Herrington DM Matrix metalloproneinases. The review of their structure and role in acute coronary syndromes. Cardiovasc Res 2003; 59 (4): 812–23.
8. Fontana V, Silva PS, Belo VA et al. Consistent alterations of circulating matrix metalloproteinases levels in untreated hypertensives and in spontaneously hypertensive rats: a relevant pharmacological target. Basic Clin Pharmacol Toxicol 2011; 109 (2): 130–7.
9. Kurdi M, Booz GW. New take on the role of angiotensin II in cardiac hypertrophy and fibrosis. Hypertension 2011; 57 (6): 1034–8.
10. Collier P, Watson CJ, Voon V et al. Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure? Eur J Heart Fail 2011; 13 (10): 1087–95.
11. de la Sierra A. Prevention of progression and regression of target organ damage. Future strategies Rev Clin Esp 2011; 211 (Suppl. 1): 8–14.
12. Smith DH. Fixed-dose combination antihypertensives and reduction in target organ damage: are they all the same? Am J Cardiovasc Drugs 2007; 7 (6): 413–22.
13. Schroeder K, Fahey T, Hay AD et al. Relationship between medication adherence and blood pressure in primary care: prospective study. J Hum Hypertens 2006; 20 (8): 625–7.
14. Menne J, Chatzikyrkou C, Haller H. Microalbuminuria as a risk factor: the influence of renin-angiotensin system blockade. J Hypertens 2010; 28 (10): 198–94.
15. Blacklock CL, Hirst JA, Taylor KS et al. Evidence for a dose effect of renin-angiotensin system inhibition on progression of microalbuminuria in Type 2 diabetes: a meta-analysis. Diabet Med 2011; 28 (10): 1182–7.
16. Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008; 372 (9638): 547–53.
17. Mallareddy M, Parikh CR, Peixoto AJ. Effect of angiotensin-converting enzyme inhibitors on arterial stiffness in hypertension: systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2006; 8(6): 398–403.
18. Vyssoulis GP, Karpanou EA, Kyvelou SM et al. Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive treatment on arterial stiffness: the role of smoking. J Clin Hypertens (Greenwich) 2008; 10 (3): 201–7.
19. Sonoda M, Aoyagi T, Takenaka K et al. A one-year study of the antiatherosclerotic effect of the angiotensin-II receptor blocker losartan in hypertensive patients. A comparison with angiotension-converting enzyme inhibitors. Int Heart J 2008; 49 (1): 95–103.
20. Ali K, Rajkumar C, Fantin F et al. Irbesartan improves arterial compliance more than lisinopril. Vasc Health Risk Manag 2009; 5 (4): 587–92.
21. Castro MM, Rizzi E, Prado CM et al. Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling. Matrix Biol 2010; 29 (3): 194–201.
22. Lim CS, Shalhoub J, Gohel MS et al. Matrix metalloproteinases in vascular disease – a potential therapeutic target? Curr Vasc Pharmacol 2010; 8 (1): 75–85.
23. Hayashi K, Sasamura H, Ishiguro K et al. Regression of glomerulosclerosis in response to transient treatment with angiotensin II blockers is attenuated by blockade of matrix metalloproteinase-2. Kidney Int 2010; 78 (1): 69–78.
24. Ishiguro K, Hayashi K, Sasamura H et al. «Pulse» treatment with high-dose angiotensin blocker reverses renal arteriolar hypertrophy and regresses hypertension. Hypertension 2009; 53 (1): 83–9.
25. Tayebjee MH, Nadar S, Blann AD et al. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Am J Hypertens 2004; 17 (9): 764–9.
26. Yamamoto D, Takai S. Pharmacological implications of MMP-9 inhibition by ACE inhibitors. Curr Med Chem 2009; 16 (11): 1349–54.
27. Cheng XW, Song H, Sasaki T et al. Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Hypertension 2011; 57 (5): 981–9.
28. Maejima Y, Okada H, Haraguchi G et al. Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma. Lab Invest 2011; 91 (6): 932–44.
29. Onal IK, Altun B, Onal ED, et al. Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment. Eur J Intern Me 2009; 20 (4): 369–72.
30. Waeber B, Feihl F, Ruilope LM Fixed-dose combinations as initial therapy for hypertension: a review of approved agents and a guide to patient selection. Drugs 2009; 69 (13): 1761–76.
31. Martin DE, DeCherney GS, Ilson BE et al. Eprosartan, an angiotensin II receptor antagonist, does not affect the pharmacodynamics of glyburide in patients with type II diabetes mellitus. J Clin Pharmacol 1997; 37 (2): 155–9.
32. Ilson BE, Boike SC, Martin DE et al. A dose-response study to assess the renal hemodynamic, vascular, and hormonal effects of eprosartan, an angiotensin II AT1-receptor antagonist, in sodium-replete healthy men. Clin Pharmacol Ther 1998; 63 (4): 471–81.
Авторы
А.В.Бушмакина*, Н.А.Козиолова, Н.А.Ковалевская
Пермская государственная медицинская академия им. акад. Е.А.Вагнера Минздравсоцразвития РФ
*E-bushmakina@mail.ru
Пермская государственная медицинская академия им. акад. Е.А.Вагнера Минздравсоцразвития РФ
*E-bushmakina@mail.ru
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A.V.Bushmakina*, N.A.Koziolova, N.A.Kovalevskaya
Acad. E.A.Vagner Perm State Medical Academy, Ministry of Health and Social Development of the Russian Federation
*E-bushmakina@mail.ru
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