Abstract
The purpose of this study is to compare the long-term effects of an angiotensin II receptor blocker (ARB) and a long-acting calcium channel blocker (CCB) on left ventricular geometry, hypertensive renal injury and a circulating marker of collagen synthesis in hypertensive patients. Patients with essential hypertension (24 men and 19 women; age, 37–79 years) were treated with a long-acting CCB, amlodipine (AML; 2.5–7.5 mg once daily) for 6 months. Then, AML was switched to an ARB, candesartan (CS; 4–12 mg once daily), in 22 patients (CS group), while AML was continued in the remaining 21 patients for another 6 months (AML group). At the end of each treatment period, ambulatory blood pressure monitoring (ABPM), echocardiography and sampling of blood and urine were performed. The average office blood pressure during the latter period was comparably controlled in the AML and the CS groups (AML: 130±8/87±7 mmHg; CS: 133±11/88±7 mmHg), while the average systolic blood pressure of 24-h ABPM was significantly lower in the AML than in the CS group (127±9 vs. 133 ±14 mmHg, p<0.05). Consequently, the left ventricular mass index was significantly decreased in the AML group (102±18 to 92±12 g/m2, p<0.05), while the change was insignificant in the CS group (103±25 to 98±21 g/m2). On the other hand, plasma procollagen I C-terminal peptide (PICP), a marker of collagen synthesis, was lowered by CS (86±21 to 70±21 ng/ml, p<0.01), but was not significantly affected by AML (80±127 to 74±91 ng/ml). CS reduced urinary albumin excretion (57±123 to 26±33 mg/g creatinine, p<0.05), but AML did not bring about significant changes (85±27 to 73±19 mg/g creatinine). The results suggested that long-acting CCBs are effective in improving left ventricular hypertrophy by controlling 24-h blood pressure, while ARBs possess protective effects against cardiovascular fibrosis and renal injury beyond their antihypertensive effects.
Similar content being viewed by others
Article PDF
References
Staessen JA, Fagard R, Thijs L, et al: Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial. Lancet 1997; 350: 757–764.
Hansson L, Zanchetti A, Carruthers SG, et al: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–1762.
Hansson L, Lindholm LH, Ekbom T, et al: Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2. Lancet 1999; 354: 1751–1756.
Dahlöf B, Devereux RB, Kjeldsen SE, et al: Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint Reduction in Hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003.
Lithell H, Hansson L, Skoog I, et al: The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–886.
Psaty BM, Heckbert SR, Koepsell TD, et al: The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 274: 620–625.
Ishikawa K, Nakai S, Takenaka T, et al: Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac events in patients with healed myocardial infarction. Circulation 1997; 95: 2368–2373.
Pitt B, Byington RP, Furberg CD, et al: Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. Circulation 2000; 102: 1503–1510.
Julius S, Kjeldsen SE, Weber M, et al: Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022–2031.
Pitt B, Poole-Wilson PA, Segal R, et al: Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582–1587.
Dickstein K, Kjekshus J : Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002; 360: 752–760.
Brewster UC, Setaro JF, Perazella MA : The renin-angiotensin-aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states. Am J Med Sci 2003; 326: 15–24.
Struthers AD, MacDonald TM : Review of aldosterone- and angiotensin II-induced target organ damage and prevention. Cardiovasc Res 2004; 61: 663–670.
Appel LJ, Stason WB : Ambulatory blood pressure monitoring and blood pressure self-measurement in the diagnosis and management of hypertension. Ann Intern Med 1993; 118: 867–882.
Hozawa A, Ohkubo T, Kikuya M, et al: Blood pressure control assessed by home, ambulatory and conventional blood pressure measurements in the Japanese general population: the Ohasama study. Hypertens Res 2002; 25: 57–63.
Kario K, Pickering TG, Umeda Y, et al: Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation 2003; 107: 1401–1406.
Devereux RB, Alonso DR, Lutas EM, et al: Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458.
Melkko J, Niemi S, Risteli L, Risteli J : Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem 1990; 36: 1328–1332.
Teppo AM : Immunoturbidimetry of albumin and immunoglobulin G in urine. Clin Chem 1982; 28: 1359–1361.
Muiesan ML, Pasini G, Salvetti M, et al: Cardiac and vascular structural changes. Prevalence and relation to ambulatory blood pressure in a middle-aged general population in northern Italy: the Vobarno Study. Hypertension 1996; 27: 1046–1052.
Palatini P, Penzo M, Racioppa A, et al: Clinical relevance of nighttime blood pressure and of daytime blood pressure variability. Arch Intern Med 1992; 152: 1855–1860.
Høegholm A, Bang LE, Kristensen KS, Nielsen JW, Holm J : Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension, and normotension. Hypertension 1994; 24: 101–105.
Suzuki Y, Kuwajima I, Kanemaru A, et al: The cardiac functional reserve in elderly hypertensive patients with abnormal diurnal change in blood pressure. J Hypertens 1992; 10: 173–179.
Darnis F, Poupon R : Pharmacokinetics and safety of single oral doses of amlodipine in patients with and without hepatic impairment: an open study. Int J Clin Pharmacol Res 1993; 13: 29–33.
Minami J, Ishimitsu T, Kawano Y, Matsuoka H : Effects of amlodipine and nifedipine retard on autonomic nerve activity in hypertensive patients. Clin Exp Pharmacol Physiol 1998; 25: 572–576.
Ishimitsu T, Minami J, Kawano Y, Numabe A, Takishita S, Matsuoka H : Amlodipine, a long-acting calcium channel blocker, attenuates morning blood pressure rise in hypertensive patients. Clin Exp Pharmacol Physiol 1999; 26: 500–504.
Clemson B, Gaul L, Gubin SS, et al: Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm. J Clin Invest 1994; 93: 684–691.
Dendorfer A, Thornagel A, Raasch W, Grisk O, Tempel K, Dominiak P : Angiotensin II induces catecholamine release by direct ganglionic excitation. Hypertension 2002; 40: 348–354.
Grassi G, Turri C, Dell'Oro R, Stella ML, Bolla GB, Mancia G : Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension. J Hypertens 1998; 16: 1789–1796.
Struck J, Muck P, Trubger D, et al: Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects. J Hypertens 2002; 20: 1143–1149.
Sato A, Saruta T : Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy. Am J Hypertens 2003; 16: 781–788.
Takai S, Jin D, Sakaguchi M, et al: Comparative effects of candesartan and amlodipine in a monkey atherosclerotic model. Hypertens Res 2004; 27: 517–522.
Burlew BS, Weber KT : Cardiac fibrosis as a cause of diastolic dysfunction. Herz 2002; 27: 92–98.
Querejeta R, Varo N, Lopez B, et al: Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease. Circulation 2000; 101: 1729–1735.
Lopez B, Querejeta R, Varo N, et al: Usefulness of serum carboxy-terminal propeptide of procollagen type I in assessment of the cardioreparative ability of antihypertensive treatment in hypertensive patients. Circulation 2001; 104: 286–291.
Dinneen SF, Gerstein HC : The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med 1997; 157: 1413–1418.
Bigazzi R, Bianchi S, Baldari D, Campese VM : Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. J Hypertens 1998; 16: 1325–1333.
Jensen JS, Feldt-Rasmussen B, Strandgaard S, Schroll M, Borch-Johnsen K : Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension 2000; 35: 898–903.
Yuyun MF, Khaw KT, Luben R, et al: Microalbuminuria independently predicts all-cause and cardiovascular mortality in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. Int J Epidemiol 2004; 33: 189–198.
Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, et al: Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004; 110: 32–35.
Kohara K, Tabara Y, Tachibana R, Nakura J, Miki T : Microalbuminuria and arterial stiffness in a general population: the Shimanami Health Promoting Program (J-SHIPP) study. Hypertens Res 2004; 27: 471–477.
Bianchi S, Bigazzi R, Baldari G, Campese VM : Microalbuminuria in patients with essential hypertension: effects of several antihypertensive drugs. Am J Med 1992; 93: 525–528.
Fauvel JP, Velon S, Berra N, et al: Effects of losartan on renal function in patients with essential hypertension. J Cardiovasc Pharmacol 1996; 28: 259–263.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishimitsu, T., Kobayashi, T., Honda, T. et al. Protective Effects of an Angiotensin II Receptor Blocker and a Long-Acting Calcium Channel Blocker against Cardiovascular Organ Injuries in Hypertensive Patients. Hypertens Res 28, 351–359 (2005). https://doi.org/10.1291/hypres.28.351
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.28.351
Keywords
This article is cited by
-
Renin-angiotensin system inhibitors in hypertensive adults with non-diabetic CKD with or without proteinuria: a systematic review and meta-analysis of randomized trials
Hypertension Research (2019)
-
Use of dihydropyridine calcium channel blockers in the management of hypertension in Eastern Asians: A scientific statement from the Asian Pacific Heart Association
Hypertension Research (2011)
-
Control of left ventricular mass by moxonidine involves reduced DNA synthesis and enhanced DNA fragmentation
British Journal of Pharmacology (2008)