Assignment: Complications of Diabetes

Increased cardiovascular risk of treated white coat and masked hypertension in patients with diabetes and chronic kidney disease: the HONEST Study Toshio Kushiro1, Kazuomi Kario2, Ikuo Saito3, Satoshi Teramukai4, Yuki Sato5, Yasuyuki Okuda5 and Kazuyuki Shimada6

The prognostic implications of treated white coat hypertension (WCH) and masked hypertension (MH) in patients with diabetes mellitus (DM) or chronic kidney disease (CKD) are not well documented. Using data from the HONEST study (n=21 591), we investigated the relationships between morning home systolic blood pressure (MHSBP) or clinic systolic blood pressure (CSBP) and cardiovascular (CV) risk in hypertensive patients with and without DM or CKD receiving olmesartan-based antihypertensive therapy. The study included 4426 DM patients and 4346 CKD patients at baseline who had 101 and 87 major CV events, respectively, during the follow-up. Compared with well-controlled non-DM patients (MHSBP o135 mmHg; CSBP o140 mmHg), DM patients with WCH (MHSBP o135 mmHg; CSBP ?140 mmHg), MH (MHSBP ?135 mmHg; CSBP o140 mmHg) or poorly controlled hypertension (PCH) (MHSBP ?135 mmHg; CSBP ?140 mm Hg) had significantly higher CV risk (hazard ratio (HR), 2.73, 2.77 and 2.81, respectively). CV risk was also significantly increased in CKD patients with WCH, MH and PCH (HR, 2.14, 1.70 and 2.20, respectively) compared with well-controlled non-CKD patients. Furthermore, DM patients had significantly higher incidence rate than non-DM patients of MHSBP ?125 to o135 mmHg (HR, 1.98) and ?135 to o145 mm Hg (HR, 2.41). In conclusion, both WCH and MH are associated with increased CV risk, and thus control of both MHSBP and CSBP is important to reduce CV risk in DM or CKD patients. The results also suggest that even lower MHSBP (o125 mm Hg) may be beneficial for DM patients, although this conclusion is limited by the small number of patients. Hypertension Research (2017) 40, 87–95; doi:10.1038/hr.2016.87; published online 11 August 2016

Keywords: cardiovascular diseases; chronic kidney disease; diabetes mellitus; masked hypertension; white coat hypertension

INTRODUCTION Home blood pressure (BP) measurement and ambulatory BP monitoring are widely used in the diagnosis and treatment of hypertension. White coat hypertension (WCH) and masked hypertension (MH) are diagnosed when there is a discrepancy between clinic BP (CBP) and home BP (HBP),1? 3 and ambulatory BP monitoring is useful in diagnosing these types of hypertension.4

The concepts of WCH and MH were originally used to describe untreated hypertensive patients based on epidemiological findings to optimize antihypertensive treatment in these patients. For example, British and Japanese guidelines recommend nonpharmacological treatment for patients with WCH and pharmacological therapy for patients with MH.5,6 For WCH patients who also have a metabolic abnormality or organ disorder, the European Society of Hypertension?European Society of Cardiology guidelines recommend pharmacological therapy.7 However, differences between BP measurements obtained at home or through ambulatory BP

monitoring and CBP may persist despite receiving antihypertensive treatment. In such cases, the patients are described as having ‘treated WCH’ or ‘treated MH’. The Home BP measurement with Olmesartan Naive patients to

Establish Standard Target blood pressure (HONEST) study is a large-scale, prospective, observational study involving more than 20 000 Japanese patients with hypertension; the aim was to investigate the relationship between HBP and CBP and the incidence of cardiovascular (CV) events in patients receiving olmesartan-based therapy.8 In our previous article describing the findings of the HONEST study, we reported a decrease in the proportion of patients with poorly controlled hypertension (PCH), that is, patients whose HBP and CBP were both high, and a consequent increase in the proportion of patients with WCH or MH after treatment with olmesartan.9 After 16 weeks, the numbers of patients in both the WCH group and the MH group were approximately double the numbers at baseline.9,10

1The Life Planning Center Foundation, Tokyo, Japan; 2Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan; 3Keio University, Yokohama, Japan; 4Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 5Daiichi Sankyo, Tokyo, Japan and 6Shin-Oyama City Hospital, Oyama, Japan Correspondence: Professor T Kushiro, The Life Planning Center Foundation, 3-12-12, Mita, Minato-ku, Tokyo 108-0073, Japan. E-mail: [email protected] Received 15 February 2016; revised 22 May 2016; accepted 31 May 2016; published online 11 August 2016

Hypertension Research (2017) 40, 87–95 Official journal of the Japanese Society of Hypertension www.nature.com/hr

Thus, we have shown that the prevalence of WCH and MH differs between untreated and treated patients. However, little information is available regarding CV risk in treated patients with WCH or MH, and guidelines for the treatment of these patients remain unclear. In patients with complications such as diabetes mellitus (DM) and … Assignment: Complications of Diabetes.