Original Article
Association of Morning and Evening Blood Pressure at Home
With Asymptomatic Organ Damage in the J-HOP Study
Satoshi Hoshide,1,2,* Kazuomi Kario,1,2,* Yuichiro Yano,1 Hajime Haimoto,3 Kayo Yamagiwa,4
Kiyoshi Uchiba,5 Shoichiro Nagasaka,6 Yoshio Matsui,7 Akira Nakamura,8 Motoki Fukutomi,1
Kazuo Eguchi,1 and Joji Ishikawa;1 on behalf of the J-HOP study group
background
Several guidelines recommend that home blood pressure (HBP) be
measured both in the morning and in the evening. However, there have
been fewer reports about the clinical significance of morning HBP than
about the clinical significance of evening HBP.
methods
Our study included 4,310 patients recruited for the Japan Morning
Surge Home Blood Pressure Study who had one or more cardiovascular
risk factors. We measured morning and evening HBP, urinary albumin–
creatinine ratio (UACR), left ventricular mass index (LVMI), brachial-ankle
pulse wave velocity (baPWV), maximum carotid intima media thickness
(IMT), N-terminal pro-brain–type natriuretic peptide (NT-proBNP), and
high-sensitivity cardiac troponin T (Hs-cTnT).
results
The correlation coefficients for the associations between morning systolic BP (SBP) and log-transformed baPWV, NT-proBNP, or Hs-cTnT were
significantly greater than the corresponding relationships for evening
SBP (all P < 0.01). The goodness-of-fit of the associations between morning home SBP and UACR (P < 0.05) or baPWV (P < 0.01) was improved
by adding evening home SBP to the SBP measurement. In contrast,
the goodness-of-fit values of the associations between evening SBP
and UACR (P < 0.001), LVMI (P < 0.05), baPWV (P < 0.001), NT-proBNP
(P < 0.001), and Hs-cTnT (P < 0.001) were improved by adding morning
home SBP to the SBP measurement.
conclusions
Morning BP and evening BP provide equally useful information for subclinical target organ damage, yet multivariate modeling highlighted
the stand-alone predictive ability of morning BP.
Keywords: blood pressure; evening blood pressure; home blood pressure; hypertension; morning blood pressure; organ damage
doi:10.1093/ajh/hpt290
Over the past decade, evidence has been mounting that selfmeasured home blood pressure (HBP) is more closely associated with hypertensive asymptomatic organ damage and
subsequent cardiovascular events than clinic BP (CBP) in both
community-dwelling populations and hypertensive patients.1–4
All recent guidelines recommend introduction of self-measured HBP monitoring (HBPM) for management of hypertension in clinical practice.1,2 Although some cohort studies on
HBPM have been published, these reports have been limited
in key respect.5–7 Two of the three cohort studies enrolled
individuals from the general population.5,6 Thus, for clinical
physicians, information on home BP (HBP) for ambulatory
high-risk patients is necessary in real-world clinical practice.
The Japan Morning Surge Home Blood Pressure
(J-HOP) Study enrolled patients who had more than one
cardiovascular risk factor and were attending ambulatory
clinics for routine checkups.8 This study has several more
robust data sets compared with previous studies.7,9,10 First,
the J-HOP study used more total BP readings than previous studies. Second, BP was measured using a validated cuff
oscillometric device with memory storage. Third, the HBP
was measured three times on each occasion (Supplementary
Table S1).
In the management of hypertension, clinicians should be
aware of the potential for various types of asymptomatic
organ damage that include, but are not limited to, cardiac
and arterial damage. Indeed, biomarkers, including the urinary albumin–creatinine ratio (UACR), brain natriuretic
peptide (BNP), pulse wave velocity (PWV), left ventricular
mass index (LVMI), and carotid intima-media thickness
Correspondence: Satoshi Hoshide ([email protected]).
*These authors contributed equally to this paper.
Initially submitted August 20, 2013; date of first revision October 7,
2013; accepted for publication December 15, 2013; online publication
January 28, 2014.
1Division of Cardiovascular Medicine, Department of Medicine, Jichi
Medical University School of Medicine, Tochigi, Japan; 2Department
of Sleep and Circadian Cardiology, Jichi Medical University School of
Medicine, Tochigi, Japan; 3Haimoto Clinic, Aichi, Japan; 4Yamagiwa Clinic,
Aichi, Japan; 5Oooka Clinic, Nagano, Japan; 6Division of Endocrinology
and Metabolism, Department of Medicine, Jichi Medical University
School of Medicine, Tochigi, Japan; 7Iwakuni City Medical Center Ishikai
Hospital, Yamaguchi, Japan; and 8Chukyo Clinical, Aichi, Japan
© American Journal of Hypertension, Ltd 2014. All rights reserved.
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American Journal of Hypertension 27(7) July 2014 939
Hoshide et al.
(IMT), have been prospectively related to the risk for
clinical cardiovascular disease events.11–15 Recently, highsensitivity cardiac troponin T (Hs-cTnT) has been associated with cardiovascular events in community-dwelling
individuals.16
Several guidelines recommend routine monitoring of
both morning and evening HBP.2,17,18 Large prospective
studies have shown that morning HBP is an independent
risk factor for cardiovascular events. Yet, few studies have
assessed the independent or incremental predictive ability
of evening HBP over morning BP for organ damage. In this
backdrop, we modeled the associations between morning
and evening HBP levels, both alone as well as together, for
preclinical cardiac and extracardiac organ damage in a large
sample of asymptomatic patients recruited for the J-HOP
study who had one or more cardiovascular risk factors. The
aim of our study was to assess the differential prognostic
significance of HBP in the morning (morning BP) and the
evening (evening BP).
METHODS
Patients for the J-HOP study were recruited consecutively
from January 2005 to May 2012 by 75 doctors at 71 institutions (45 primary practices, 22 hospital-based outpatient
clinics, and 4 specialized university hospitals) throughout
Japan. The ethics committee of the internal review board of
the Jichi Medical University School of Medicine, Tochigi,
Japan, approved the protocol. The study protocol was registered on a clinical trials registration site (University Hospital
Medical Information Network Clinical Trials Registry,
UMIN000000894). Written informed consent was obtained
from all patients enrolled in the study.
Study subjects
Between January 2005 and May 2012, we enrolled 4,310
ambulatory outpatients who had one or more of the following cardiovascular risks: hypertension, hyperlipidemia, diabetes (fasting blood sugar 126 mg/dl and/or current use of an
antidiabetic drug), glucose intolerance, metabolic syndrome,
chronic kidney disease (estimated glomerular filtration rate
<60 ml/min/1.73 m2), history of cardiovascular disease (coronary artery disease, stroke, aortic dissection, peripheral
artery disease, congestive heart failure), atrial fibrillation,
current smoking, chronic obstructive pulmonary disease, or
sleep apnea syndrome. We excluded patients who had malignancy or chronic inflammatory disease.
We asked study patients to measure their morning HBP
(measured after awakening and before breakfast and taking
antihypertensive medication) and evening HBP (measured
before taking antihypertensive medication and going to
bed) in a sitting position for a 2-week period. All data in the
HBPM device were downloaded to a computer and sent to
the study control center (Jichi Medical University, Tochigi).
The averages of all HBPs measured three times in the morning (morning HBP) and three times in the evening (evening HBP) for 14 days (84 readings in total) were separately
calculated by the study coordinator, who was blinded to the
study participants’ clinical characteristics.
Clinic BP was measured at the clinic using the same device
and calculated as the average of three consecutive measurements. We advised patients to take their morning medication as usual on the days when they were to visit the clinic.
Echocardiography, ultrasonographic measurements of the
carotid artery, and pulse wave velocity
Echocardiography was performed at each participating
institution. Two-dimensional M-mode or B-mode images
were obtained using an ultrasound machine according to the
guidelines of the American Society of Echocardiology and
the European Association of Echocardiography.19 The LVM
was obtained using the formula validated by the American
Society of Echocardiology: LVM = 0.8 (1.04 ([LVIDD +
PWTD +IVSTD]3 − [LVIDD]))3 + 0.6 g, where LVIDD is
the diastolic LV dimension, PWTD is the diastolic posterior
wall diameter, and IVSTD is the diastolic interventricular
septal diameter. The LVMI was calculated as LV mass/body
surface area. At each participating institution, the carotid
intima-media thickness was assessed for the right and left
common carotid artery using a B-mode ultrasound scanner.
Carotid IMT was measured at 3 points proximal to the bilateral carotid bulb (far wall) in 10-mm segments at end-diastole and always in plaque-free segments. If plaque existed
at the IMT measuring point, an appropriate adjacent portion was chosen. The mean of the right and left maximum
carotid IMT (6 points total) was used in the analysis (max
IMT). The brachial-ankle PWV (baPWV) was measured
using the volume plethysmographic method with previously
validated equipment (form PWV/ABI; Omron Healthcare
Co, Ltd, Kyoto, Japan). The details of the measurements
and the reproducibility of this automatic method have been
described elsewhere.20 We used the mean of right and left
baPWV values for the analysis.
Biomarker assays
BP measurements
HBP was measured using a validated cuff oscillometric
device (HEM-5001; Medinote, Omron Healthcare, Kyoto,
Japan)8 according to the Hypertension Guidelines for the
Management of Hypertension.2,17,18 This HBPM device automatically takes three measurements at 15-s intervals on each
occasion. All recorded BP parameters were stored separately
according to whether they were measured in the morning,
evening, or during sleep.
940 American Journal of Hypertension 27(7) July 2014
The measurement method of biomarker assays is described
in the Supplementary Materials.
Statistical analysis
All analyses were performed for all 4,310 patients, and
the data were expressed as the means (± standard deviation)
or percentages. For some patients, measurements of some
organ damage were also obtained for an optional substudy.
Home Blood Pressure and Organ Damage
In the current study, the UACR of 4,296 patients, LVMI
of 1,845 patients, baPWV of 2,695 patients, max IMT of
1,356 patients, N-terminal pro-brain−type natriuretic peptide (NT-proBNP) of 3,643 patients, and Hs-cTnT of 3,635
patients were finally used. Details of the statistical analyses
performed are provided in the Supplementary Materials.
RESULTS
Patient characteristics
Table 1 shows the characteristics of the patients in this
study. The mean age was 64.8 ± 10.9 years, and 47.0% were
men. The prevalences of regular alcohol use, smoking,
hyperlipidemia, and diabetes mellitus were 28.0%, 12.0%,
40.7%, and 23.5%, respectively; 79.1% of the subjects were
using antihypertensive medication.
HBP and asymptomatic organ damage
Both morning and evening systolic BP (SBP) levels were significantly associated with all organ damages
(Supplementary Table S2). A comparison of the correlation coefficients from these relationships demonstrates that
a more accurate index of baPWV (P < 0.01), NT-proBNP
(P < 0.001), and Hs-cTnT (P < 0.01) was provided by morning SBP than by evening SBP. With regard to diastolic BP
(DBP), both morning and evening DBP were positively
associated with log UACR, while both BPs were negatively
associated with baPWV, max IMT, log NT-proBNP, and
log Hs-cTnT (Supplementary Table S2). In multiple linear
regression analyses, morning SBP was independently associated with all organ damages after adjusting for covariates.
Evening SBP was independently associated with UACR,
LVMI, baPWV, NT-proBNP, and Hs-cTnT but not max IMT
(Table 2). With regard to DBP, morning DBP was independently associated with log UACR, whereas it had the effect
of suppressor in relation to baPWV, log NT-proBNP, and log
Hs-cTnT. Evening DBP was independently associated with
log UACR, whereas it had the effect of suppressor in relation
to baPWV (Supplementary Table S3).
Joint association of morning and evening BP with
organ damage
In a multiple linear regression model of SBP, the goodnessof-fit of the relationship between SBP and UACR was incrementally improved by adding each SBP measure to clinic
SBP (and confounding factors) in the following order: morning SBP and evening SBP. This association was also found in
baPWV. However, addition of evening SBP did not improve
the goodness-of-fit of the relationships between SBP and
LVMI, max IMT, NT-proBNP, or Hs-cTnT (Table 3). With
regard to DBP, adding evening DBP improved the goodness-of-fit of the relationships between DBP and baPWV
and NT-proBNP (Supplementary Table S4). To investigate
whether there was a change in the goodness-of-fit of the linear relationship between BP and hypertensive organ damage induced by adding each SBP measure to clinic SBP (and
confounding factors), we added morning and evening BP in
reverse order in multiple linear regression model of SBP. The
goodness-of-fit of the relationships between SBP and UACR,
LVMI, baPWV, NT-proBNP, and Hs-cTnT was incrementally
improved by adding morning SBP (Table 4). With regard to
DBP, adding morning DBP improved the goodness-of-fit of
the relationships between DBP and log UACR, NT-proBNP
and Hs-cTnT (Supplementary Table S5). Next, we evaluated
the association between binary outcome of organ damage
and morning or evening BP level using area under the curve
(AUC). The prevalence of microalbuminuria (UACR >30 mg/g
Cr), LVH (LVMI >115 g/m2 in men and >95 g/m2 in women),
abnormal baPWV (>1,750 cm/s), carotid atherosclerosis (max
IMT ≥1.1 mm), abnormal NT-proBNP (>400 pg/ml), and
abnormal Hs-cTnT (>0.014 ng/ml) was 25.4%, 36.4%, 34.8%,
29.3%, 4.0%, and 8.4%, respectively. There was no difference
in AUC for organ damage between morning SBP and evening SBP (UACR, 0.63 vs. 0.62; LVMI, 0.59 vs. 0.60; baPWV,
0.68 vs. 0.65; max IMT, 0.55 vs. 0.54; NT-proBNP, 0.57 vs.
0.53; Hs-cTnT, 0.61 vs. 0.57), although AUC of morning SBP
tended to be higher than that of evening SBP except for LVMI.
When we divided morning and evening BPs into tertiles and
compared the prevalence of binary outcome of organ damage
between the highest tertile of morning and evening BPs, significant differences were not found (data not shown).
Discussion
We have shown in nationwide ambulatory Japanese
patients that HBPs were associated with asymptomatic
organ damage. In multivariate analyses, morning and evening BPs are equally associated with organ damage. Adding
the measurement of evening SBP to morning SBP improved
the goodness-of-fit of the association between SBP and
UACR or PWV, while this association was not found for
other organ damage markers. On the other hand, adding the
measurement of morning SBP to evening SBP improved the
goodness-of-fit of the association between SBP and organ
damage markers except for max IMT. The strength of the
present investigation was its large sample size and use of
nationwide ambulatory patients, six markers of asymptomatic organ damage, and an HBPM device with memory
storage.
Morning BP and organ damage
Cross-sectional observations of hypertensive patients
have demonstrated a strong association between increasing
morning BP level and vascular damage throughout the circulatory system, including the myocardium, large arteries, and
other organs.21–26 Our results support the findings of these
previous studies. This is the first study to show an association
between morning BP measured at home and organ damage
in a large number of ambulatory patients. Previously we
assessed the impact of targeted treatment of morning BP on
microalbuminuria by bedtime administration of the alphaadrenergic blocker doxazosin.27 The reduction of UACR as
a marker of asymptomatic organ damage was significantly
associated with the use of doxazosin, the baseline morning
American Journal of Hypertension 27(7) July 2014 941
Hoshide et al.
Table 1. Baseline characteristics of study subjects
Characteristic
Number of participants in the J-HOP study, n = 4,310
Age, y
64.8 ± 10.9
Male, %
Body mass index,
47.0
kg/m2
24.3 ± 3.5
Waist/hip ratio
0.90 ± 0.07
Alcohol, %
28.0
Smoking, %
12.0
Dyslipidemia, %
40.7
Diabetes, %
23.5
Past history, %
Angina
7.2
Myocardial infarction
3.9
Aortic dissection
0.7
Stroke
4.1
Congestive heart failure
1.7
Peripheral artery disease
1.0
Arterial fibrillation
3.7
Chronic kidney disease, estimated glomerular filtration rate <60 ml/min/1.73
m2,
%
20.4
Antihypertensive drug, %
79.1
Calcium antagonist
50.8
Angiotensin converting enzyme inhibitor
6.6
Angiotensin II receptor blockers
51.8
Beta blocker
13.7
Alfa blocker
5.0
Diuretics
26.1
Aldosterone blocker
2.2
Statin, %
23.6
Aspirin, %
15.1
Clinic systolic blood pressure, mm Hg
141.3 ± 16.5
Clinic diastolic blood pressure, mm Hg
81.2 ± 10.6
Morning systolic blood pressure, mm Hg
138.4 ± 15.9
Morning diastolic blood pressure, mm Hg
79.1 ± 10.0
Evening systolic blood pressure, mm Hg
130.1 ± 15.0
Evening diastolic blood pressure, mm Hg
72.7 ± 9.7
Urinary albumin/creatinine ratio, mg/g Cr (n = 4,296)
13.2 [7.2, 30.8]
Left ventricular mass index, g/m2 (n = 1,845)
101 ± 16.9
Brachial-ankle pulse wave velocity, cm/s (n = 2,695)
1,675 ± 352
Maximum carotid intima-media thickness, mm (n = 1,356)
0.96 ± 0.24
N-terminal pro-brain–type natriuretic peptide, pg/ml (n = 3,643)
50.4 [25.5, 97.4]
High-sensitivity cardiac troponin T, ng/ml (n = 3,635)
0.003 [0.003, 0.007]
Data are shown as the means ± standard deviation, medians [25%, 75%], or percentages.
BP, and the change in morning BP; these associations were
independent of each other. In clinical practice, therefore, we
conclude that it is necessary to evaluate and control morning BP in order to prevent the progression of organ damage.
942 American Journal of Hypertension 27(7) July 2014
Evening BP and organ damage
This study showed that evening BP was independently
associated with organ damage after adjusting for covariates.
Home Blood Pressure and Organ Damage
Table 2. Associations between organ damage and clinic, morning, and evening systolic blood pressure
log UACR, mg/g Cr
Model 1
Model 2
Model 3
Max IMT, mm
Standardized β
P
Tolerance
VIF
R2
Clinic SBP
0.147
<0.001
0.72
1.38
0.166
Morning SBP
0.177
<0.001
0.68
1.47
Clinic SBP
0.169
<0.001
0.76
1.32
Evening SBP
0.140
<0.001
0.72
1.38
Clinic SBP
0.140
<0.001
0.70
1.42
Morning SBP
0.143
<0.001
0.40
2.52
Evening SBP
0.050
<0.05
0.42
2.38
0.159
0.167
Standardized β
P
Tolerance
VIF
−0.009
0.77
0.74
1.35
0.063
<0.05
0.69
1.46
0.003
0.93
0.80
1.25
0.044
0.14
0.77
1.30
−0.010
0.75
0.73
1.37
0.056
0.16
0.42
2.38
0.011
0.77
0.47
2.12
LVMI, g/m2
Model 1
Model 2
Model 3
Standardized β
P
Tolerance
VIF
R2
Clinic SBP
0.096
<0.001
0.72
1.39
0.106
Morning SBP
0.137
<0.001
0.69
1.44
Clinic SBP
0.107
<0.001
0.76
1.32
Evening SBP
0.123
<0.001
0.72
1.38
Clinic SBP
0.088
<0.01
0.70
1.42
Morning SBP
0.096
<0.01
0.40
Evening SBP
0.061
0.07
0.42
P
Tolerance
VIF
0.019
0.27
0.72
1.39
0.140
<0.001
0.67
1.49
0.049
0.01
0.75
1.33
0.082
<0.001
0.72
1.40
0.020
0.24
0.70
1.43
2.51
0.147
<0.001
0.39
2.60
2.40
−0.011
0.63
0.41
2.44
0.104
0.107
baPWV cm/s
Model 1
Model 2
Model 3
0.098
0.097
0.098
log NT-proBNP, pg/ml
Standardized β
Standardized β
R2
R2
0.263
0.255
0.263
log Hs-cTnT, ng/ml
P
Tolerance
VIF
R2
Standardized β
0.411
P
Tolerance
VIF
−0.028
0.11
0.72
1.40
0.128
<0.001
0.67
1.49
−0.001
0.94
0.75
1.33
0.079
<0.001
0.72
1.40
Clinic SBP
0.244
<0.001
0.73
1.37
Morning SBP
0.149
<0.001
0.70
1.43
Clinic SBP
0.243
<0.001
0.76
1.33
Evening SBP
0.160
<0.001
0.74
1.36
Clinic SBP
0.230
<0.001
0.71
1.41
−0.027
0.13
0.70
1.44
Morning SBP
0.072
<0.01
0.39
2.58
0.131
<0.001
0.39
2.60
Evening SBP
0.113
<0.001
0.41
2.46
−0.004
0.86
0.41
2.44
0.414
0.416
R2
0.199
0.193
0.199
Abbreviations: baPWV, brachial-ankle pulse wave velocity; Hs-cTnT, high-sensitivity cardiac troponin T; LVMI, left ventricular mass index;
max IMT, maximum carotid intima-media thickness of carotid artery; NT-proBNP, N-terminal pro-brain–type natriuretic peptide; SBP, systolic
blood pressure; UACR, urinary albumin/creatinine ratio; VIF, variance inflation factor.
No prior investigation has evaluated the association between
evening BP and different markers of organ damage because
most previous studies used an average of morning and evening BP and a small series.28–31 A large number of ambulatory
patients and multiple asymptomatic organ damages have
not been studied. In real-world clinical practice, the difference between measuring both morning and evening BP and
measuring either morning or evening BP would depend on
individuals’ lifestyles. If patients measure evening BP without
measuring morning BP, physicians should use measured evening BP as a good indicator of management for hypertension.
Joint consideration of morning and evening BP for
assessment of organ damage
The present study showed that morning SBP improved the
goodness-of-fit of the association between evening SBP and
organ damage markers except in the case of max IMT. This is
the first study to show that morning SBP is significantly associated with asymptomatic organ damage, as has been found
for evening SBP, in a large number of ambulatory patients.
This study showed that addition of evening home SBP did
not enhance the ability of morning SBP to predict LVMI,
max IMT, NT-proBNP, or Hs-cTnT. The fact that morning
BP had a greater clinical impact on organ damage compared
with evening BP might have been related to the effects of
antihypertensive treatment. The patients with higher morning BP might be affected by an insufficient duration of action
of antihypertensive treatment; about 80% of the patients in
our study were treated. In treated patients, control of morning BP is important for regression of organ damage.
In contrast, evening SBP enhanced the ability of morning SBP to predict UACR and baPWV. It is not clear why the
improvement of evening SBP was different with organ damage.
American Journal of Hypertension 27(7) July 2014 943
Hoshide et al.
Table 3. Change in the goodness-of-fit of the linear relationship between blood pressure and organ damage induced by adding evening
systolic blood pressure
Organ damage
log UACR
LVMI
baPWV
Max IMT
log NT-proBNP
log Hs-cTnT
Model
Change in R2
Change in F
P value for the change in model
Confounders + clinic SBP
0.148
52.407
<0.001
Model 1 + morning SBP
0.021
108.544
<0.001
Model 2 + evening SBP
0.001
5.411
<0.05
Confounders + clinic SBP
0.100
14.527
<0.001
Model 1 + morning SBP
0.013
26.857
<0.001
Model 2 + evening SBP
0.002
3.252
Confounders + clinic SBP
0.399
125.479
<0.001
Model 1 + morning SBP
0.016
70.654
<0.001
Model 2 + evening SBP
0.005
23.78
<0.001
Confounders + clinic SBP
0.106
11.322
<0.001
Model 1 + morning SBP
0.003
4.077
<0.05
Model 2 + evening SBP
<0.001
0.085
0.77
0.253
86.757
<0.001
Model 1+ morning SBP
0.013
64.306
<0.001
Model 2+ evening SBP
<0.001
0.234
0.63
Confounders + clinic SBP
0.07
Confounders + clinic SBP
0.191
60.59
<0.001
Model 1+ morning SBP
0.011
49.737
<0.001
Model 2+ evening SBP
<0.001
0.03
0.86
Model 1 included age, sex, body mass index, waist-hip ratio, diabetes mellitus, hyperlipidemia, smoking, alcohol use, chronic renal damage,
past history of cardiovascular disease, antihypertensive medication use, and clinic SBP. Model 2 included age, sex, body mass index, waist-hip
ratio, diabetes mellitus, hyperlipidemia, smoking, alcohol use, chronic renal damage, past history of cardiovascular disease, antihypertensive
medication use, clinic SBP, and morning SBP.
Abbreviations: baPWV, brachial-ankle pulse wave velocity; Hs-cTnT, high-sensitivity cardiac troponin T; LVMI, left ventricular mass index;
max IMT, maximum carotid intima-media thickness of carotid artery; NT-proBNP, N-terminal pro-brain–type natriuretic peptide; SBP, systolic
blood pressure; UACR, urinary albumin/creatinine ratio.
Systemic BP is a significant determinant of arterial stiffness
and affects the escape of albumin from the renal glomerulus.32 The contribution of BP overload might be dramatic for a
change in UACR and baPWV, which are linked to each other
in an indirect contribution of endothelial function.33,34 In addition, we previously reported that in an interventional study, the
lowering of evening HBP was associated more closely with the
reduction of UACR in patients with prediabetes/diabetes compared with the association between UACR and morning HBP,
while this association was not found in nondiabetic patients.35
In high-risk patients, tight control of both morning and evening HBP might be important for prevention of kidney damage.
Several guidelines, including Japanese guidelines, have recommended that HBP be measured both in the morning and
in the evening.2,17,18 Two large cohort studies have reported
that HBP in the morning has greater clinical significance
than HBP in the evening.9,10 The Ohasama study in a single
rural community in Japan demonstrated that morning and
evening HBPs seemed to provide equally useful information
for assessing cardiovascular risk.9 The Finn-home study has
also reported that morning and evening BPs could be equally
predictive of future cardiovascular events.10 However, these
studies did not determine whether morning BP and evening BP provide different information on the development of
organ damage. Recognition of the association between organ
944 American Journal of Hypertension 27(7) July 2014
damage and HBP profiles could help to clarify the effect of BP
on organ damage through pathophysiological processes and
support physicians when they make clinical decisions about
whether to control morning or evening BP.
There are some limitations of this study. First, it was a crosssectional study of the association between HBP measurement
and organ damage, and thus the prognostic value of HBP
measurement, including antihypertensive treatment, needs to
be confirmed by a study based on cardiovascular morbidity
and mortality. Second, the slight increases in R2 from model
1 to model 2 plus morning or evening SBP, as shown in Tables
3 and 4, raise concern about multicollinearity among the different BP measurements, although the value of the variance
inflation factor for each variable seems not to be an issue. In
addition, HBPM provides multiple BP readings. Therefore,
their variability must also be evaluated, if necessary. Several
studies have reported that day-by-day variability assessed
using HBPM was associated with organ damage in hypertensive and diabetic patients.36,37 As the literature proving this
point is overwhelming, the current study focused on the association between average HBP level and organ damage.
When both morning BP and evening BP were measured at
home following established guidelines, both BPs were associated with organ damage. Measuring evening BP in addition
to morning BP improves the association between SBP and
Home Blood Pressure and Organ Damage
Table 4. Change in the goodness-of-fit of the linear relationship between blood pressure and organ damage induced by adding morning
systolic blood pressure
Organ damage
log UACR
LVMI
baPWV
Max IMT
log NT-proBNP
log Hs-cTnT
Model
Change in R2
Change in F
P value for the change in model
Model 1 + evening SBP
0.014
71.886
<0.001
Model 2 + morning SBP
0.008
41.494
<0.001
Model 1 + evening SBP
0.011
22.444
<0.001
Model 2 + morning SBP
0.004
7.618
<0.01
Model 1 + evening SBP
0.019
85.693
<0.001
Model 2 + morning SBP
0.002
9.087
<0.01
Model 1 + evening SBP
0.001
2.201
0.14
Model 2 + morning SBP
0.001
1.957
0.16
Model 1 + evening SBP
0.005
23.516
<0.001
Model 2 + morning SBP
0.008
40.75
<0.001
Model 1 + evening SBP
0.004
19.891
<0.001
Model 2 + morning SBP
0.007
29.703
<0.001
Model 1 included age, sex, body mass index, waist-hip ratio, diabetes mellitus, hyperlipidemia, smoking, alcohol use, chronic renal damage,
past history of cardiovascular disease, antihypertensive medication use, and clinic SBP. Model 2 included age, sex, body mass index, waist-hip
ratio, diabetes mellitus, hyperlipidemia, smoking, alcohol use, chronic renal damage, past history of cardiovascular disease, antihypertensive
medication use, clinic SBP, and evening SBP.
Abbreviations: baPWV, brachial-ankle pulse wave velocity; Hs-cTnT, high-sensitivity cardiac troponin T; max IMT, maximum carotid intimamedia thickness of carotid artery; NT-proBNP, N-terminal pro-brain–type natriuretic peptide; SBP, systolic blood pressure; UACR, urinary albumin/creatinine ratio; LVMI, left ventricular mass index;.
organ damage markers, which contributes to BP overload,
such as UACR and baPWV. On the other hand, measuring
morning BP in addition to evening BP improves the association between SBP and organ damage markers. Different
guidelines recommend the measurement of evening BP at
different times,2,17,18 because there are racial and individual
differences related to daily customs and culture, such as
bathing, time of dinner, and drinking alcohol. In Western
countries, evening BP is reported to be slightly higher than
morning BP in untreated hypertensive patients.38 However,
in the current study, morning BP was significantly higher
than evening BP, as has been shown in previous studies in
Japan.9 Although morning BP and evening BP have equal
association with organ damage, only measurement of evening BP is likely to underestimate the risk of organ damage
in individuals from Japan. In conclusion, morning BP and
evening BP provide equally useful information for subclinical target organ damage, yet multivariate modeling highlighted the stand-alone predictive ability of morning BP.
SUPPLEMENTARY MATERIAL
Supplementary materials are available at American Journal
of Hypertension (http://ajh.oxfordjournals.org).
Acknowledgments
This study was financially supported, in part, by a grant
from the 21st Century Center of Excellence Project, which
is operated by Japan’s Ministry of Education, Culture,
Sports, Science, and Technology (MEXT); a grant from the
Foundation for Development of the Community (Tochigi);
and, in part, by a grant from Omron Healthcare Co., Ltd., by
grant-in-aid for scientific research (B; 21390247) from the
MEXT, Japan, to K.K., 2009–2013, and by MEXT-supported
program for the Strategic Research Foundation at Private
Universities, 2011–2015.
Contributors
Kazuomi Kario is the principle investigator of the J-HOP
study, supervised its conduct and data analysis and had primary responsibility for the writing of this paper. Satoshi
Hoshide, the secretary in general of the J-HOP, conducted
all statistical analyses.
Participants and participating centers
Kazuomi Kario: Jichi Medical University School of
Medicine; Satoshi Hoshide: Jichi Medical University School
of Medicine; Hajime Haimoto: Haimoto Clinic; Kayo
Yamagiwa: Yamagiwa Clinic; Kiyoshi Uchiba: Oooka Clinic;
Syouichirou Nagasaka: Jichi Medical University School of
Medicine; Yuichiro Yano: Nango Clinic; Kazuo Eguchi: Jichi
Medical University School of Medicine and International
University of Health and Welfare Hospital; Yoshio Matsui:
Jichi Medical University and Hagi city Mishima Clinic;
Motohiro Shimizu: Ogi city Fukukawa Clinic and Heigun
Clinic; Ryou Nakamura: Chukyo Clinic; Joji Ishikawa:
Jichi Medical University School of Medicine and Koga
Red Cross Hospital; Shizukiyo Ishikawa: Jichi Medical
American Journal of Hypertension 27(7) July 2014 945
Hoshide et al.
University School of Medicine and Washiya Hospital; Motoki
Fukutomi: Simonoseki city Tsunoshima Clinic; Tomoyuki
Kabutoya: Jichi Medical University School of Medicine
and Ojikano Central Hospital and Chichibu Municipal
Hospital; Kyousei Souda: Souda Clinic; Michiaki Nagai:
Syoubara Red Cross Hospital and Syoubara city National
Health Insurance Clinic; Seiichi Sibazaki: Ogi city Fukukawa
Clinic; Hideyuki Uno: Jichi Medical University School of
Medicine and Noda Hospital; Sachiyo Ogata: Joriku-Omiya
Saiseikai Hospital; Yoshifumi Nojiri: Joetsu Community
Medical Center Hospital; Ryuji Inoue: Kanzaki General
Hospital; Kazuhiko Kotani: Tottori University Hospital;
Satoshi Yamada: Yamada Clinic; Takeshi Mitsuhashi: Jichi
Medical University School of Medicine; Hiroaki Tsukao:
Yamashita Clinic; Tetsuya Aoki: Akasaki Clinic; Toshio
Kuroda: Kuroda Internal Medicine and Cardiovascular
Clinic; Yutaka Nakajima: Shimonoseki city Toyota Central
Hospital; Akinori Hirai: Nagahama Red Cross Hospital;
Hareaki Yamamoto: Yamamoto Clinic; Tsuneo Oowada:
Oowada Internal Medicine and Gastrointestinal Clinic;
Masaru Ichida: Jichi Medical University School of Medicine;
Setsuko Katou: Katou Clinic of Internal Medicine; Takahiro
Komori: Jichi Medical University School of Medicine and
Utsunomiya Social Insurance Hospital and Kurai Kiyohiko
Memorial Hospital; Sigeki Nishizawa: Nishizawa Clinic
of Internal Medicine; Kazuhiro Murata: Ooshima Clinic;
Takashi Utsu: Shiga Medical University; Toru Kato: Koyanagi
Memorial Hospital; Osamu Kuwasaki: Kuwasaki Clinic of
Internal Medicine; Yutaka Shimada: Kyaranoki Care Center;
Yoshihiro Yonezawa: Yonezawa Clinic; Eiji Inoue: Inoue
Clinic of Internal Medicine; Masatoshi Matsumoto: Jichi
Medical University School of Medicine; Toru Kimura: Iiduka
Clinic; Kenichi Sakakura: Kumano city Kiwa Clinic; Shingo
Shikano: Ibuki Shikano Clinic; Kazuhiro Handa: Handa
Clinic; Kouichirou Abe: Abe Clinic of Internal Medicine;
Motoyuki Ishiguro: Ishiguro Clinic; Yoshio Onogaki:
Onogaki Clinic; Hiroshi Kubo: Hiro Clinic of Cardiovascular
Medicine and Gastrointestinal Medicine; Kouichi Tokai:
Kamihira Clinic; Ryou Touji: Touji Clinic; Akiya Nakamoto:
Nakamoto Clinic of Internal Medicine; Youichi Ehara: Yoshii
Chuo Clinic; Masahiro Toshima: Kamiichi General Hospital;
Nobuyuki Adachi: Adachi Clinic of Internal Medicine; Nobuo
Takahashi: Takahashi Family Clinic; Masashi Tanaka: Manba
Clinic; Fumihiko Eto: Privcare Family Clinic; Masahisa
Shinpo: Jichi Medical University School of Medicine;
Katsumi Tanaka: Youga Urban Clinic; Takeshi Takemi: Clinic
Jingu-Mae; Masayuki Nagata: Nakata Clinic; Yukihiro Hojo:
Jichi Medical University School of Medicine; Yoko Hoshide:
Satou Clinic; Fumihiko Yasuma: Suzuka National Hospital;
Hajime Yanagisawa: Sudou Hospital; Yukitaka Anraku:
Omocyanomachi Internal Medicine Clinic; Shuichi Ueno:
Jichi Medical University School of Medicine; Ryousuke
Kusaba: Saitama Tsukuba Hopistal; Naoshi Suzuki: Washiya
Hospital; and Nobuyuki Maki: Kamogawa City National
Health Insurance Hospital.
DISCLOSURE
The authors declared no conflict of interest.
946 American Journal of Hypertension 27(7) July 2014
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American Journal of Hypertension 27(7) July 2014 947