Received: 15 August 2019 | Accepted: 27 August 2019

DOI: 10.1111/jch.13713

RE VIE W PAPER

Asian management of hypertension: Current status, home

blood pressure, and specific concerns in Japan

Tomoyuki Kabutoya MD, PhD | Satoshi Hoshide MD, PhD | Kazuomi Kario MD, PhD

Division of Cardiovascular
Medicine, Department of Medicine, Jichi
Medical University School of Medicine,
Tochigi, Japan
Correspondence
Kazuomi Kario, MD, PhD, Division of
Cardiovascular Medicine, Department of
Medicine, Jichi Medical University School of
Medicine, Tochigi, Japan.
Email: kkario@jichi.ac.jp
Funding information
This work was supported by Pfizer, Omron
Healthcare, and the Kanae Foundation for
the Promotion of Medical Science.
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 com‐
monly used antihypertensive agents are calcium channel blockers followed by angio‐
tensin 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 effec‐
tively 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 hyper‐
tension phenotypes. Information and communication technology‐based monitoring
platforms and wearable devices are expected to facilitate better management of hy‐
pertension in Japan in the future.

1 | C A R D I OVA S CU L A R D I S E A S E a stroke mortality rate of 13.2%, and a poor physical functioning

I N C I D E N C E A N D H Y PE RTE N S I O N
M A N AG E M E NT I N JA PA N
Hypertension prevalence rates in Japan are high—60% for males
and 45% for females.1 In Japan, stroke is a major cause of cardio‐
vascular events, and reduced quality of life due to stroke is a seri‐
ous 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. 2-5 Data from 2017 showed
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 sys‐
tolic BP (SBP) decreases the stroke and heart failure mortality rates
by 27% and 28%, respectively.7 BP reduction therefore has an im‐
portant impact on decreasing the occurrence of stroke and heart
failure, and plays a central role in reducing cardiovascular events
among Japanese.

486 | © 2019 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/jch J Clin Hypertens. 2020;22:486–492.

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KABUTOYA et al. | 487

2 | CU R R E NT S TAT U S O F H B PM I N TH E
M A N AG E M E NT O F H Y PE RTE N S I O N I N
JA PA N
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
1
was <140/90 mm Hg and the target home BP was <135/85 mm Hg.
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 moni‐
tor 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
10
morning BP of <135 mm Hg. 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 cardiovas‐
cular event risk.
3 | JA PA N S U B ‐A N A LYS I S O F TH E
A S I A B P @ H O M E S T U DY
The 2017 American College of Cardiology (ACC)/American Heart
Association (AHA) guidelines reduced the diagnostic and target of‐
fice 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

Conventional thresholds Japan (n=100) r=0.35 New thresholds

Masked Sustained Masked Sustained

(uncontrolled) (uncontrolled) (uncontrolled) (uncontrolled)
morning hypertension morning hypertension
hypertension hypertension
9% 24%
7% 10%

White-coat White-coat
(uncontrolled) (uncontrolled)
64% hypertension 39%
Well-controlled 20% Well-controlled 27% hypertension

Well-controlled clinic SBP 71% Well-controlled clinic SBP 49%

Well-controlled morning home SBP 84% Well-controlled morning home SBP 66%

F I G U R E 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

488 | KABUTOYA et al.
using conventional BP thresholds (office SBP 140 mm Hg and morn‐
ing 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
14
with the 2017 ACC/AHA guidelines). Well‐controlled hypertension
was defined as normal office/clinic and home BP, white‐coat hyper‐
tension 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 guide‐
lines, 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 morn‐
ing 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 cri‐
teria, 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.
4 | P OS ITI O N I N G O F H B PM I N TH E
JA PA N E S E H Y PE RTE N S I O N G U I D E LI N E S
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 meas‐
ure their home BP. Patients with home SBP ≥ 135 mm Hg and/or
17517176, 2020, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jch.13713 by Nat Prov Indonesia, Wiley Online Library on [14/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
DBP ≥ 85 mm Hg were definitively diagnosed as having hyperten‐
sion (apart from those for whom HBPM was not available or feasi‐
ble). 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 | TR A D ITI O N A L A NTI H Y PE RTE N S I V E
TH E R A PY A N D P O PU L A R
A NTI H Y PE RTE N S I V E D RU G S I N JA PA N
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 nutri‐
tional 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 block‐
ers (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 fluc‐
tuations 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
F I G U R E 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.caren​et.com/serie​s/
hakus​ho/cg002​384_index.html)
 17517176, 2020, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jch.13713 by Nat Prov Indonesia, Wiley Online Library on [14/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
KABUTOYA et al. | 489

F I G U R E 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.caren​et.com/serie​s/
hakus​ho/cg002​384_index.html)

C

490 | KABUTOYA et al.
classes of antihypertensive agents.7 However, a recent claims da‐
tabased study showed that antihypertensive prescription in Japan
did not always follow current guidelines. In addition, drug pre‐
scriptions varied based on patient age and comorbidities, and the
size of the treating institution. 21
The pharmacological effects of antihypertension drugs based on
the timing of their administration and circadian BP variation (chro‐
notherapy) also need to be considered as part of effective antihyper‐
tensive 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),
12
indicating that olmesartan is a potent and long‐acting drug.
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
23
Organ Protection (J‐TOP) study. There was a significantly greater
reduction in the urine albumin‐to‐creatinine ratio (UACR) in the bed‐
time dosing group (−45.7% vs −34.5% in the morning dosing group;
23
P = .02).
6 | S PEC I FI C CO N C E R N S A N D
PE R S PEC TI V E S FO R H Y PE RTE N S I O N
M A N AG E M E NT I N JA PA N
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 thresh‐
olds 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 vari‐
ability are important targets for antihypertensive therapy, 27-32 which
must be monitored using out‐of‐office BP monitoring (HBPM and/
or ambulatory BP monitoring).33-35 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 clini‐
cal practice.37-39 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 hyper‐
tension management in Japan is likely to be based on information
and communication technology‐based monitoring devices and wear‐
able technologies.40-43
17517176, 2020, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jch.13713 by Nat Prov Indonesia, Wiley Online Library on [14/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
AC K N OW L E D G M E N T S
English language editing assistance was provided by Nicola Ryan, in‐
dependent medical writer, funded by the HOPE Asia Network.
C O N FL I C T O F I N T E R E S T
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 submit‐
ted work. Tomoyuki Kabutoya has received scholarship fund from
Mitsubishi Tanabe Pharma Corporation. The other authors have no
conflicts of interest to report.
AU T H O R C O N T R I B U T I O N S
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.
ORCID
Satoshi Hoshide https://orcid.org/0000-0001-7541-5751
Kazuomi Kario https://orcid.org/0000-0002-8251-4480
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492 | KABUTOYA et al.

supine position according to the ANSI/AAMI/ISO81060‐2:2013

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HEM‐6410T‐ZL. J Clin Hypertens (Greenwich). 2019;21:853‐858.