Asian management of hypertension: Current status, home blood pressure, and specific concerns in Japan

Abstract

Hypertension is highly prevalent in Japan, affecting up to 60% of males and 45% of females. Stroke is the main adverse cardiovascular event, occurring at a higher rate than acute myocardial infarction. Reducing blood pressure (BP) therefore has an important role to play in decreasing morbidity and mortality. The high use of home BP monitoring (HBPM) in Japan is a positive, and home BP is a better predictor of cardiovascular event occurrence than office BP. New 2019 Japanese Society of Hypertension Guidelines strongly recommend the use of HBPM to facilitate control of hypertension to new lower target BP levels (office BP < 130/80 mm Hg and home BP < 125/75 mm Hg). Lifestyle modifications, especially reducing salt intake, are also an important part of hypertension management strategies in Japan. The most commonly used antihypertensive agents are calcium channel blockers followed by angiotensin receptor blockers, and the combination of agents from these two classes is the most popular combination therapy. These agents are appropriate choices in South East Asian countries given that they have been shown to reduce stroke more effectively than other antihypertensives. Morning hypertension, nocturnal hypertension, and BP variability are important targets for antihypertensive therapy based on their association with target organ damage and cardiovascular events. Use of home and ambulatory BP monitoring techniques is needed to monitor these important hypertension phenotypes. Information and communication technology‐based monitoring platforms and wearable devices are expected to facilitate better management of hypertension in Japan in the future.

1. CARDIOVASCULAR DISEASE INCIDENCE AND HYPERTENSION MANAGEMENT IN JAPAN

Hypertension prevalence rates in Japan are high—60% for males and 45% for females.1 In Japan, stroke is a major cause of cardiovascular events, and reduced quality of life due to stroke is a serious problem in Japan's aging society. The age‐adjusted mortality rate of Japanese stroke patients is approximately 3‐4 times higher than that of acute myocardial infarction.2, 3, 4, 5 Data from 2017 showed a stroke mortality rate of 13.2%, and a poor physical functioning prognosis.6 Heart failure mortality is also high, due to an increase in the aging population with heart failure. The reduction in the rate of cardiovascular events due to a 10‐mm Hg reduction in blood pressure (BP) is approximately 20%, but the same reduction in systolic BP (SBP) decreases the stroke and heart failure mortality rates by 27% and 28%, respectively.7 BP reduction therefore has an important impact on decreasing the occurrence of stroke and heart failure, and plays a central role in reducing cardiovascular events among Japanese.

2. CURRENT STATUS OF HBPM IN THE MANAGEMENT OF HYPERTENSION IN JAPAN

Home BP monitoring (HBPM) is widely used in Japan. The Ohasama Study (a general population cohort study) first demonstrated that home BP was superior to office BP measurement for predicting cardiovascular events.8 In the previous Japanese guidelines (2014), target office BP for a patient aged <75 years with no comorbidities was <140/90 mm Hg and the target home BP was <135/85 mm Hg.1 In contrast, the new 2019 version of the Japanese Society of Hypertension guidelines has reduced the office BP target to <130/80 mm Hg and the home BP to <125/75 mm Hg.9 In addition, the new guidelines strongly recommend the use of a home BP monitor to facilitate control of hypertension to new lower target BP levels (office BP < 130/80 mm Hg and home BP < 125/75 mm Hg).9

These recommendations are based on a good body of local evidence. In the Japan Morning Surge‐Home Blood Pressure (J‐HOP) study, which enrolled high cardiovascular risk patients, the increase in cardiovascular event risk associated with home morning BP of 135‐144 mm Hg was 2.5 times that associated with a home morning BP of <135 mm Hg.10 Using < 125 mm Hg as a reference, the home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study, reported that the hazard ratio for cardiovascular events was 2.15 when morning home BP was 145‐155 mm Hg and 6.24 when morning home BP was 155 mm Hg.11 Also in the HONEST study, of those with office SBP < 130 mm Hg, patients with morning home BP ≥ 140 mm Hg had a 2.47‐fold increase in the cardiovascular event rate compared to those with morning home BP < 125 mm Hg.12 Overall, cardiovascular event risk was lowest in patients with morning home SBP of 124 mm Hg, and morning home SBP > 144 mm Hg was significantly associated with an increase in the rate of cardiovascular events.12 In a risk‐stratified sub‐analysis of the HONEST study population, lower achieved home SBP was associated with reduced cardiovascular disease risk, and the lowest risk was seen in patients with a home SBP < 125 mm Hg.13 Based on the results of these studies, we propose that morning home BP should be controlled <145 mm Hg. We also suggest that it is better to reduce morning home BP to <125 mm Hg to decrease cardiovascular event risk.

3. JAPAN SUB‐ANALYSIS OF THE ASIABP@HOME STUDY

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines reduced the diagnostic and target office BP thresholds to 130/80 mm Hg; the definition of hypertension based on home BP also uses a level of 130/80 mm Hg.14

Japan enrolled 100 patients into the Asia BP@Home Study.15, 16 Overall, the 1443 patients enrolled into the study were classified using conventional BP thresholds (office SBP 140 mm Hg and morning home SBP 135 mm Hg, consistent with the Japanese Society of Hypertension [JSH] 2014 guidelines),1 and strict thresholds (office SBP 130 mm Hg and morning home SBP 130 mm Hg, consistent with the 2017 ACC/AHA guidelines).14 Well‐controlled hypertension was defined as normal office/clinic and home BP, white‐coat hypertension was defined as normal home SBP and elevated office SBP, masked hypertension was defined as normal office SBP and elevated home SBP, and sustained hypertension was defined as elevated BP in the office and at home.

When patients were classified according to the JSH 2014 guidelines, 64% of patients had well‐controlled hypertension, 20% had white‐coat hypertension, 7% had masked hypertension, 9% had sustained hypertension, and 16% had uncontrolled home morning BP (Figure 1). Rates for classification based on the 2017 ACC/AHA guidelines were 39% for well‐controlled hypertension, 27% for white‐coat hypertension, 10% for masked hypertension, 24% for sustained hypertension, and 34% of patients had uncontrolled home morning BP (Figure 1). Thus, when the home BP threshold was changed from the JSH 2014 criteria to the 2017 ACC/AHA criteria, the percentage of patients with uncontrolled home morning BP increased from 16% to 34% and the percentage of patients with white‐coat hypertension increased from 20% to 27%. Clinicians should carefully consider the treatment of the increased number of individuals with white‐coat hypertension.

Figure 1.

Distributions of blood pressure (BP) control status based on different clinic and morning home BP thresholds in the Japan sub‐analysis from the AsiaBP@Home study. Left panel represents the results based on cut‐off values of 140 mm Hg for clinic systolic BP (SBP) and 135 mm Hg for home SBP. Right panel represents the results based on cut‐off values of 130 mm Hg for both clinic SBP and home SBP

4. POSITIONING OF HBPM IN THE JAPANESE HYPERTENSION GUIDELINES

In the JSH 2014 guidelines, hypertension was defined as office SBP ≥ 140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg, and home SBP ≥ 135 mm Hg and/or DBP ≥ 85 mm Hg.1 Patients with office SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg were advised to measure their home BP. Patients with home SBP ≥ 135 mm Hg and/or DBP ≥ 85 mm Hg were definitively diagnosed as having hypertension (apart from those for whom HBPM was not available or feasible). These criteria are revised in the new 2019 JSH Guidelines for the Management of Hypertension,9 which more closely reflect the 2017 ACC/AHA criteria and recommendations.14 Use of HBPM is recommended to achieve these targets.

5. TRADITIONAL ANTIHYPERTENSIVE THERAPY AND POPULAR ANTIHYPERTENSIVE DRUGS IN JAPAN

Hypertension is influenced by lifestyle habits, and therefore lifestyle modifications have a role in preventing hypertension and reducing BP.17, 18 In the JSH 2014 guidelines, salt reduction, weight control, exercise, reducing alcohol intake, and quitting smoking are described as lifestyle modifications. Of these, reduction of salt intake is the most useful lifestyle modification for lowering BP. Intensive nutritional information aimed at reducing salt intake by 6 g/day reduced BP to a significantly greater extent than standard salt restriction education in a Japanese study.19

First‐choice agents specified in the JSH 2014 guidelines are calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), angiotensin‐converting enzyme (ACE) inhibitors, and diuretics.1 CCBs have always been the most commonly used agents as monotherapy in Japan, although there have been fluctuations over time, particularly related to the increased use of ARBs after their introduction in 2009 (Figure 2).20 If combination therapy is required, the JSH 2019 guidelines recommend the use of CCB + ARB/ACE inhibitor, ARB/ACE inhibitor +diuretics, or CCB + diuretics. Irrespective of previous therapy, CCB + ARB is the most commonly used combination in Japan (Figure 3A‐C). This is appropriate given that stroke is more common than myocardial infarction in South East Asian countries, and that CCBs and ARBs have been shown to reduce stroke more effectively than other classes of antihypertensive agents.7 However, a recent claims databased study showed that antihypertensive prescription in Japan did not always follow current guidelines. In addition, drug prescriptions varied based on patient age and comorbidities, and the size of the treating institution.21

Figure 2.

Agents used for antihypertensive monotherapy in Japan over time.20 ACE, angiotensinc‐converting enzyme; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; JSH, Japanese Society of Hypertension. (Reprinted with permission from CareNet, Inc https://www.carenet.com/series/hakusho/cg002384_index.html)

Figure 3.

Approaches to combination antihypertensive therapy when monotherapy with a calcium channel blocker (CCB) (A) or angiotensin receptor blocker (ARB) (B), or combination therapy with a CCB + ARB (C) is insufficient. (Reprinted with permission from CareNet, Inc https://www.carenet.com/series/hakusho/cg002384_index.html)

The pharmacological effects of antihypertension drugs based on the timing of their administration and circadian BP variation (chronotherapy) also need to be considered as part of effective antihypertensive therapy and cardiovascular risk reduction strategies. In the HONEST Study, olmesartan significantly reduced both office BP and morning home SBP to similar degrees (by approximately 20 mm Hg), indicating that olmesartan is a potent and long‐acting drug.12 Azilsartan has also been shown to significantly reduce morning BP (and to a greater extent than candesartan) in Japanese patients with essential hypertension.22 Dosing of candesartan at bedtime or on awakening was investigated in the Japan Morning Surge‐Target Organ Protection (J‐TOP) study.23 There was a significantly greater reduction in the urine albumin‐to‐creatinine ratio (UACR) in the bedtime dosing group (−45.7% vs −34.5% in the morning dosing group; P = .02).23

6. SPECIFIC CONCERNS AND PERSPECTIVES FOR HYPERTENSION MANAGEMENT IN JAPAN

The number of patients with severe hypertension has been falling, and therefore most of the excess morbidity among stroke patients is shifting from those with severe hypertension to those with mild hypertension.7 In addition, more than half of the excess death and morbidity of cardiovascular disease due to high BP occurs in the mildly high BP category.24, 25 Therefore, lifestyle modifications and preventing the onset of hypertension have become more important in patients with high‐normal BP or stage 1 hypertension.

Lowering BP thresholds is a useful public health strategy that shifts the BP distribution to lower values.26 Using the new thresholds might facilitate individualized antihypertensive treatment, which in turn could help to prevent cardiovascular events. Based on their association with target organ damage and cardiovascular events, morning hypertension, nocturnal hypertension, and BP variability are important targets for antihypertensive therapy,27, 28, 29, 30, 31, 32 which must be monitored using out‐of‐office BP monitoring (HBPM and/or ambulatory BP monitoring).33, 34, 35 The recent J‐HOP Nocturnal study was the first to demonstrate that high nocturnal home BP is associated with increased risk of stroke independently of office and morning home BP.36 Nocturnal HBPM is easily introduced in clinical practice.37, 38, 39 In addition, masked uncontrolled hypertension is a high‐risk condition, and thus the detection of masked hypertension is very important in clinical practice settings. The future of hypertension management in Japan is likely to be based on information and communication technology‐based monitoring devices and wearable technologies.40, 41, 42, 43

CONFLICT OF INTEREST

Kario K received research grant from A &D Co.; Omron Helthcare Co.; Roche Diagnostics KK; MSD KK; Astellas Pharma Inc; Otsuka Holdings Co.; Otsuka Pharmaceutical Co.; Sanofi KK; Shionogi & Co.; Sanwa Kagaku Kenkyusho Co.; Daiichi Sankyo Co.; Sumitomo Dainippon Pharma Co.; Takeda Pharmaceutical Co.; Mitsubishi Tanabe Pharma Co.; Teijin Pharma; Boehringer Ingelheim Japan Inc; Pfizer Japan Inc; Fukuda Denshi Co.; Fukuda Lifetec Co.; Fukuda Lifetec Kanto Co.; Bristol‐Myers Squibb KK; Mylan Co.; Mochida Pharmaceutical Co.; IQVIA Services Japan KK and honoraria from Omron Healthcare Co.; Daiichi Sankyo Co.; Takeda Pharmaceutical Co.; Terumo Co.; Idorsia Pharmaceuticals Japan outside the submitted work. Tomoyuki Kabutoya has received scholarship fund from Mitsubishi Tanabe Pharma Corporation. The other authors have no conflicts of interest to report.

AUTHOR CONTRIBUTIONS

Conception and design: T. Kabutoya and K. Kario. Drafting of the manuscript or critical revision for important intellectual content: T. Kabutoya, S. Hoshide, K. Kario. Final approval of the submitted manuscript: T. Kabutoya, S. Hoshide, K. Kario.

Kabutoya T, Hoshide S, Kario K. Asian management of hypertension: Current status, home blood pressure, and specific concerns in Japan. J Clin Hypertens. 2020;22:486–492. 10.1111/jch.13713