Atherosclerosis 207 (2009) 186–190 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Effect of losartan on ambulatory short-term blood pressure variability and cardiovascular remodeling in hypertensive patients on hemodialysis Hiroshi Mitsuhashi a , Kouichi Tamura a,∗ , Junji Yamauchi a , Motoko Ozawa a , Mai Yanagi a , Toru Dejima a , Hiromichi Wakui a , Shin-ichiro Masuda a , Koichi Azuma a , Tomohiko Kanaoka a , Masato Ohsawa a , Akinobu Maeda a , Yuko Tsurumi-Ikeya a , Yasuko Okano a , Tomoaki Ishigami a , Yoshiyuki Toya a , Yasuo Tokita b , Toshimasa Ohnishi a , Satoshi Umemura a a Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan b Renal Division, Department of Medicine, Fujisawa Municipal Hospital, Fujisawa, Japan article info Article history: Received 17 January 2009 Received in revised form 31 March 2009 Accepted 1 April 2009 Available online 11 April 2009 Keywords: Angiotensin II type 1 receptor blocker Ambulatory blood pressure Blood pressure variability Hemodialysis Left ventricular hypertrophy Advanced glycation end product Natriuretic peptide Pulse wave velocity abstract Objective: Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether an angiotensin II type 1 receptor blocker losartan would improve ambulatory short-term BP variability in hypertensive patients on hemodialysis. Methods: Forty hypertensive patients on hemodialysis therapy were randomly assigned to the losartan treatment group (n = 20) or the control treatment group (n = 20). At baseline and 6 and 12 months after the treatment, 24-h ambulatory BP monitoring was performed. Echocardiography and measurements of brachial-ankle pulse wave velocity (baPWV) and biochemical parameters were also performed before and after therapy. Results: After 6- and 12-months of treatment, nighttime short-term BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased in the losartan group, but remained unchanged in the control group. Compared with the control group, losartan significantly decreased left ventricular mass index (LVMI), baPWV, and the plasma levels of brain natriuretic peptide and advanced glycation end products (AGE). Furthermore, multiple regression analysis showed signifi- cant correlations between changes in LVMI and changes in nighttime short-term BP variability, as well as between changes in LVMI and changes in the plasma levels of AGE. Conclusion: These results suggest that losartan is beneficial for the suppression of pathological cardiovas- cular remodeling though its inhibitory effect on ambulatory short-term BP variability during nighttime. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Cardiovascular disease is the main cause of death in patients with advanced chronic kidney disease, and hypertension is a major risk factor for cardiovascular disease in these patients [1]. In particular, findings of pathological cardiovascular remodeling such as left ventricular hypertrophy and atherosclerosis are fre- quently found during dialysis therapy, and have been identified as independent risk factors for mortality [2,3]. Cardiovascular remodeling is an adaptive response to hemodynamic as well as non- ∗ Corresponding author at: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. Tel.: +81 45 787 2635; fax: +81 45 701 3738. E-mail address: tamukou@med.yokohama-cu.ac.jp (K. Tamura). hemodynamic stimuli, such as hypertension and vasoactive agents. Thus, the intensive management of hypertension is critically impor- tant for the prevention of pathological cardiovascular remodeling in patients on dialysis therapy. Ambulatory blood pressure (BP) monitoring allows the acquisi- tion of critical information on not only the average 24-h BP, but also the variations in BP values that take place in the course of daily life. Among the several parameters obtained by ambulatory BP monitoring, previous studies have shown that BP variability is a complex phenomenon that involves both short- and long-lasting changes [4]. Thus the 24-h BP varies not only because of a reduction in BP during nighttime sleep and increase in the morning, but also because of sudden, quick, and short-lasting changes that occur both during the day and, to a lesser extent, at night. This phenomenon, short-term BP variability, has been shown to depend on sympa- thetic vascular modulation and on atherosclerotic vascular changes [4,5]. Short-term BP variability is suggested to be clinically relevant 0021-9150/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2009.04.005