The MUSCAT Study: A Multicenter PROBE Study Comparing the Effects of Angiotensin II Type-1 Receptor Blockers on Self-Monitored Home Blood Pressure in Patients with Morning Hypertension: Study Design and Background Characteristics

51 Hypertens Res Vol.31 (2008) No.1 p.49-56 Original Article The MUSCAT Study: A Multicenter PROBE Study Comparing the Effects of Angiotensin II Type-1 Receptor Blockers on Self-Monitored Home Blood Pressure in Patients with Morning Hypertension: Study Design and Background Characteristics Haruhito UCHIDA1), Yoshio NAKAMURA2), Masanobu KAIHARA1), Hisanao NORII1), Yoshihisa HANAYAMA1), and Hirofumi MAKINO1) Elevated morning home blood pressure (MHBP) has been reported to have a close relationship to cerebrocardiovascular events and hypertensive target organ damages, and hence is regarded as a predictor of cardiovascular events. However, there is no evidence that lowering of MHBP can improve morbidity, mortality or target organ damage. In recent guidelines, angiotensin II type-1 receptor blockers (ARBs) are recommended as the first-choice drugs for antihypertensive therapy. Pharmacological characteristics differ among ARBs, and some are suggested to have greater efficacy in lowering MHBP than others. In preparation for the MUSCAT study, we surveyed both self-monitored MHBP and office blood pressure (OBP) in 1,234 patients with essential hypertension. Among them, 367 patients had diabetes mellitus (DM) and 229 suffered from chronic kidney disease (CKD). More than 64% (n = 790) of patients had morning hypertension. In MUSCAT, we will investigate the different effects of four ARBs (losartan, candesartan, valsartan, and telmisartan) in patients with morning hypertension, with a focus on the drugs’ MHBP-lowering efficiency. Secondly, we will evaluate the different actions of the four ARBs on cardiovascular surrogate markers, such as the brachial-ankle pulse wave velocity, high-sensitive C-reactive protein level, and urinary albumin excretion/creatinine ratio. Patients will be randomized into four arms, and given one of the four “sartans” once daily for 12 months. MHBPs and surrogate markers will be examined at baseline and after 1 year of followup. In the stratified analysis, we will determine the significance of MHBP reduction on cardiovascular risk management. (Hypertens Res 2008; 31: 51–58) Key Words: telmisartan, candesartan, valsartan, losartan, microalbuminuria Introduction Hypertension is one of the major risk factors of cardiovascular disease (1, 2). Treatment of hypertension reduces morbidity and mortality, preserves organ function and prevents cardiovascular complications. Based on many evidences, some guidelines recommend that blood pressure (BP) should be suppressed to below target levels, which depend on risk factors and complications (3–6). It has been shown that earlymorning hypertension has a close relation to cerebrocardiovascular events (7, 8). Also, it has been reported that morning From the 1)Department of Medicine and Clinical Science and 2)Department of Laboratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Address for Reprints: Yoshio Nakamura, M.D., Department of Laboratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2–5–1 Shikata-cho, Okayama 700–8558, Japan. E-mail: Received February 2, 2007; Accepted in revised form August 3, 2007. 52 Hypertens Res Vol. 31, No. 1 (2008) Table 1. Outpatient Background Age (years) Sex (male/female) OBP (mmHg) MHBP (mmHg) BMI (kg/m2) Smoking (%) Dyslipidemia (%) Diabetes (%) IHD (%) Stroke (%) CKD (%) Hyper uricemia (%) Habitual drinking (%) NT (n=244) WHT (n=200) MHT (n=306) CHT (n=484) 63 110/134 126/75 125/77 24.1 19 49 29 9 6 18 12 27 65 75/125 152/83 127/77 24.3 16 50 22 9 9 12 9 20 68* 132/174 129/74 149/84 24.1 18 47 35* 10 10 21* 13 27 67* 233/251 155/84 153/84 24.5 18 43 30 10 10 20* 14 28 p value <0.001 n.s. n.s. n.s. n.s. <0.05 n.s. n.s. <0.05 n.s. n.s. home blood pressure (MHBP) is related to organ dysfunctions such as left ventricular hypertrophy (9), microalbuminuria (10), silent cerebral infarcts (11) and carotid intima-media thickness (12). In addition, masked hypertension has been shown to be associated with hypertensive target organ damages (13, 14), and is regarded as a predictor of cardiovascular events (15, 16). Thus, the importance of MHBP has increased in clinical practice, although there is no actual evidence that lowering MHBP to ideal levels can improve morbidity, mortality or target organ damage. Morning BP can be measured either using an ambulatory BP monitoring (ABPM) device or by self-monitoring with a manometer. ABPM has been used to evaluate morning BP, but it has been reported that the reproducibility of ambulatory BP measurement is poor and that the evaluation of the efficacy and duration of antihypertensive drugs on the basis of ABPM is affected by several effects, including the placebo effect (17, 18). Because of both the development of devices for home BP measurement and the establishment of practical guidelines, self-measured BP has recently been used in clinical settings (19). Angiotensin II type-1 receptor blockers (ARBs) are recommended as the first-choice agents for antihypertensive therapy in the guidelines mentioned above. However, it has been suggested that the efficacy and duration of action differ among ARBs. For example, we previously reported that the antihypertensive effect of telmisartan is stronger and longer than that of losartan, and sufficient to decrease MHBP based on self-monitored MHBP measurements (20). Other authors observed different durations of action and different efficacies among four ARBs examined herein (21). Further, some studies have shown differences in antihypertensive effect among ARBs using ABPM (22–24). However, these studies have all Morning Home Blood Pressure NT, normotensive; WHT, white-coated hypertensive; MHT, masked hypertensive; CHT, continuous hypertensive; OBP, office blood pressure, MHBP, morning home blood pressure; BMI, body mass index; IHD, ischemic heart disease; CKD, chronic kidney disease. p value are analyzed using 1-way ANOVA. mmHg 240 220 200 MHT 24.8% CHT 39.2% n=1234 r=0.264 p<0.001 180 160 140 120 100 NT 19.8% WHT 16.2% 80 80 100 120 140 160 Office Blood Pressure 180 200 220 mmHg Fig. 1. The distribution of systolic blood pressure (SBP) in the 1,234 patients with hypertension. There was a significant but weak relationship between office SBP and morning home SBP. NT, normotensive; WHT, white-coat hypertensive; MHT, masked hypertensive; CHT, continuous hypertensive. p values were analyzed by a single regression analysis. been relatively short, with durations of about 1 month or, in the case of our own previous study, no more than 3 months. Therefore, in this Multicenter PROBE Study Comparing the Effects of Angiotensin II Type-1 Receptor Blockers on Self-Monitored Home Blood Pressure in Patients with Morning Hypertension (MUSCAT study), we aim to evaluate the long-term efficacy and duration of action on MHBP of four ARBs in patients with morning hypertension. In add (...truncated)