Circ J 2017; 81: 1647 – 1653 ORIGINAL ARTICLE

doi: 10.1253/circj.CJ-16-1306
Epidemiology

Morning and Evening Blood Pressures Are Associated With

Intima-Media Thickness in a General Population
― The Hisayama Study ―

Satoko Sakata, MD, PhD; Jun Hata, MD, PhD; Masayo Fukuhara, MD, PhD; Koji Yonemoto, PhD;
Naoko Mukai, MD, PhD; Daigo Yoshida, PhD; Hiro Kishimoto, PhD; Toshio Ohtsubo, MD, PhD;
Takanari Kitazono, MD, PhD; Yutaka Kiyohara, MD, PhD; Toshiharu Ninomiya, MD, PhD

Background:  The association of morning and evening home blood pressures (HBPs) with carotid atherosclerosis has been uncer-
tain in general populations, so we aimed to investigate it in a general Japanese population.

Methods and Results:  We performed a cross-sectional survey of 2,856 community-dwelling individuals aged ≥40 years to examine
the association of morning and evening HBPs with carotid mean intima-media thickness (IMT). The age- and sex-adjusted geometric
averages of carotid mean IMT increased significantly with increasing morning HBP (optimal: 0.67 mm; normal: 0.69 mm; high normal:
0.72 mm; grade 1 hypertension: 0.74 mm; and grade 2+3 hypertension: 0.76 mm) and with increasing evening HBP (0.68 mm,
0.71 mm, 0.73 mm, 0.76 mm, and 0.78 mm, respectively) (both P for trend <0.001). These associations remained significant even after
adjusting for potential confounding factors. Likewise, both isolated morning hypertension (morning HBP ≥135/85 mmHg and evening
HBP <135/85 mmHg) and isolated evening hypertension (evening HBP ≥135/85 mmHg and morning HBP <135/85 mmHg) as well as
sustained hypertension (both morning and evening HBP ≥135/85 mmHg) were significantly associated with thicker mean IMT.

Conclusions:  Our findings suggested that both morning and evening HBPs were significantly associated with carotid atherosclero-
sis in this general Japanese population.

Key Words: Atherosclerosis; Epidemiology; Home blood pressure; Intima-media thickness

M
easuring home blood pressure (HBP) is becom-
ing common for hypertensive patients in clinical
practice. HBP measurement can reduce observer
biases and white-coat effects, and is useful to assess the
duration of the effectiveness of antihypertensive medica-
tion and to improve adherence to antihypertensive treat-
ment.1–5 In addition, HBP has been reported to be more
sensitive for risk assessment of target organ damage than
casual blood pressure (BP) measured at the clinic or health
examination.6–9 BP has a circadian rhythm caused by neu-
roendocrine factors.10,11 Circadian rhythm is also affected
by antihypertensive medication, and lifestyle factors.12–14
Therefore, it is important to measure HBP on different
occasions. Several recent guidelines or scientific statements
for hypertension management have recommended measuring
HBP at least twice daily, namely, in the morning and in the
evening.3–5,15 Most clinical studies have evaluated the asso-
ciation of HBP with target organ damage using average
values of either morning and evening HBPs16–18 or only
morning HBP.19,20 Meanwhile, there are limited numbers
of studies addressing the influence of morning HBP and
evening HBP separately on atherosclerotic disease in general
populations, as the clinical significance of morning HBP
and evening HBP may be different.
The purpose of the present study was to investigate the
association of HBP levels in the morning and evening with
carotid atherosclerosis in a general Japanese population.
Methods
Study Population
The Hisayama Study is a population-based observational
study for cardiovascular disease, which was established in
1961 in the town of Hisayama, a suburb of the Fukuoka

Received December 21, 2016; revised manuscript received April 14, 2017; accepted May 9, 2017; released online June 14, 2017  
Time for primary review: 25 days
Department of Epidemiology and Public Health (S.S., J.H., N.M., D.Y., H.K., T.N.), Center for Cohort Studies (J.H., N.M., D.Y.,
H.K., T.K., T.N.), Department of Medicine and Clinical Science (S.S., J.H., N.M., T.O., T.K.), Graduate School of Medical
Sciences, Kyushu University, Fukuoka; Division of General Internal Medicine, Kyushu Dental University, Kitakyushu (M.F.);
Advanced Medical Research Center, Faculty of Medicine, University of the Ryukyus, Okinawa (K.Y.); and Hisayama Research
Institute for Lifestyle Diseases, Fukuoka (Y.K.), Japan
Mailing address:  Jun Hata, MD, PhD, Department of Epidemiology and Public Health, Graduate School of Medical Sciences,
Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.   E-mail: junhata@eph.med.kyushu-u.ac.jp
ISSN-1346-9843   All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp

Circulation Journal  Vol.81, November 2017

1648
metropolitan area on Kyushu Island, Japan.21–23 In 2007
and 2008, a total of 3,384 residents of Hisayama aged 40
years or older participated in health examinations (par-
ticipation rate among the total population of this age
group: 78.2%). After the exclusion of 8 participants who
refused to participate in the epidemiological study, 453
subjects without HBP measurements for more than 3 days,
and 67 without information on carotid ultrasonography, a
total of 2,856 subjects (1,234 men and 1,622 women) were
enrolled in the present study.
Home and Clinical BP Measurements
The procedure for the measurement of HBP was described
in detail in our previous report24 and followed the Japanese
guidelines for self-monitoring of BP at home.3 HBP
was measured using an automatic device (HEM-7080IC;
Omron Healthcare Co., Ltd.) based on the validated cuff
oscillometric method. This device uses the identical com-
ponents and BP-determining algorithm as another device,
HEM-705IT, which was previously validated and satisfied
the criteria of the British Hypertension Society protocol.25
The subjects were instructed to measure their HBP 3 times
every morning before breakfast within 1 h of waking and 3
times every evening before going to bed after more than
5 min of rest while seated, for 4 weeks. Subjects on antihy-
pertensive medication were instructed to measure their
HBP before taking their medication. Morning and evening
HBPs were defined as the mean value of daily averages of
HBP in the morning and in the evening, respectively. In
addition, clinical BP was measured 3 times at the health
examination using an automated sphygmomanometer
(BP-203 RVIIIB; Omron Healthcare Co., Ltd.), and the
mean of 3 measurements was used for the analysis.
Classification of Groups Based on HBP
HBP was categorized by the measured values, regardless
antihypertensive medication. In the present analysis, we
defined HBP from the European Society of Hypertension
and European Society of Cardiology (ESH-ESC) criteria4
minus 5 mmHg, because HBP of 135/85 mmHg is consid-
ered to be equivalent to clinical BP of 140/90 mmHg. For
each morning and evening HBP, values were classified into
5 categories as follows: optimal (HBP <115/75 mmHg);
normal (HBP 115–124/75–79 mmHg); high normal
(HBP 125–134/80–84 mmHg); grade 1 hypertension (HBP
135–154/85–94 mmHg); grade 2+3 hypertension (HBP
≥155/95 mmHg). The subjects were also divided into 4
groups according to the combination of morning and eve-
ning HBP: normotension (morning HBP <135/85 mmHg
and evening HBP <135/85 mmHg), isolated morning hyper-
tension (morning HBP ≥135/85 mmHg and evening HBP
<135/85 mmHg), isolated evening hypertension (morning
HBP <135/85 mmHg and evening HBP ≥135/85 mmHg),
and sustained hypertension (morning HBP ≥135/85 mmHg
and evening HBP ≥135/85 mmHg). Furthermore, for the
sensitivity analysis, the subjects were re-categorized into 4
groups using a different cutoff value of 126/76 mmHg for
evening HBP, which corresponded to morning HBP of
135/85 mmHg in a linear regression analysis between morn-
ing and evening HBP (Figure S1), in order to correct for
the imbalance in the number of subjects with isolated eve-
ning hypertension.
Carotid Ultrasonography
Carotid ultrasonography was performed using a real-time,
Circulation Journal  Vol.81, November 2017
SAKATA S et al.
B-mode ultrasound imaging unit (Toshiba Sonolayer
SSA-250A; Toshiba, Tokyo, Japan) with a 7.5-MHz annu-
lar array probe as described previously.24 Mean intima-
media thickness (IMT) was measured using the long-axis
views of the right and left common carotid arteries. We
examined the far wall of each common carotid artery in the
region that was 20 mm proximal to the origin of the bulb,
and automatically calculated the average IMT as the mean
value of IMT measurements on each side using a com-
puter-assisted measurement system (Intimascope; Media
Cross Co., Ltd, Tokyo, Japan).26 Mean IMT was defined
as the mean of the average IMT of the left and right sides.
Maximum IMT in the observation-possible areas of the
left and right common carotid arteries, bulbs, and internal
carotid arteries was measured manually. Carotid wall thick-
ening was defined as a maximum IMT >1.0 mm. Moreover,
advanced carotid wall thickening was determined as a
maximum IMT >1.5 mm.
Other Risk Factors
At the health examination, each participant completed a
self-administered questionnaire covering medical history,
antihypertensive medication, lipid-lowering medication,
smoking habit, alcohol intake, and regular exercise. Smoking
habit and alcohol intake were classified as either current
use or not. Subjects engaging in sports or other forms of
exertion ≥3 times a week during their leisure time made up
the regular exercise group. Body height and weight were
measured in light clothing without shoes, and the body
mass index (BMI: kg/m2) was calculated. Serum total and
high-density lipoprotein (HDL) cholesterol levels were
determined enzymatically. Blood glucose levels were mea-
sured by the hexokinase method. Diabetes mellitus was
determined as fasting glucose level ≥7.0 mmol/L, postpran-
dial or 2-h postload glucose level ≥11.1 mmol/L, or use of
antidiabetic medication.
Statistical Analysis
The correlation between morning or evening HBP and
clinical BP was evaluated using Pearson’s correlation coef-
ficient. The differences in the mean values of continuous
variables or frequencies of categorical variables across the
morning or evening HBP categories were examined using
an analysis of variance or a logistic regression model. Mean
and maximum IMT were transformed into logarithm to
improve skewness, and geometrical means were reported
by back transformation. The adjusted geometric averages
of the mean and maximum IMT across the morning or
evening HBP categories were assessed using an analysis of
covariance. The age- and sex-adjusted prevalence of carotid
wall thickening was calculated using the direct method,
using the distributions of age and sex in the study popula-
tion as a reference population. The age- and sex-adjusted
or multivariable-adjusted odds ratio and its 95% confi-
dence interval (CI) for the presence of carotid wall thicken-
ing were estimated using a multivariable logistic regression
model. The subgroup analyses by antihypertensive medica-
tion status and by drinking status were conducted, and the
heterogeneity in the effects of BP levels on outcomes
between the subgroups was estimated by adding interac-
tion terms to the relevant statistical model. The hetero-
geneity in the association with carotid atherosclerosis
between morning and evening HBPs was tested by adding
an interaction term in the relevant statistical model with
generalized estimating equations in order to account for
Home BP and Atherosclerosis 1649

Table 1.  Clinical Characteristics of Participants According to Morning HBP Levels

Morning HBP level
Grade 1 Grade 2+3 P for
Optimal Normal High normal trend
hypertension hypertension
(n=513) (n=458) (n=587)
(n=891) (n=407)
Age, years 55±10 61±11 63±11 66±11 69±12 <0.001
Men, % 25.0 39.5 45.8 49.8 52.1 <0.001
Morning home systolic BP, mmHg 107±6　　 119±3　　　　 129±4　　　　 142±7　　　　 162±11　　 <0.001
Morning home diastolic BP, mmHg 66±5 72±5　　 77±6　　 82±7　　 89±11 <0.001
Evening home systolic BP, mmHg 105±7　　 115±8　　　　 123±8　　　　 131±11　　 147±15　　 <0.001
Evening home diastolic BP, mmHg 62±6 67±6　　 70±7　　 73±8　　 78±11 <0.001
Antihypertensive medication, % 4.1 12.7 29.5 45.1 57.3 <0.001
Diabetes mellitus, % 4.5 12.0 16.9 22.6 25.3 <0.001
Total cholesterol, mmol/L 5.4±0.9 5.5±1.0 5.5±0.9 5.4±0.9 5.4±0.9 0.34
HDL-cholesterol, mmol/L 1.9±0.5 1.8±0.4 1.7±0.4 1.7±0.4 1.7±0.5 <0.001
Lipid-lowering medication, % 7.6 9.8 17.4 20.9 18.9 <0.001
Body mass index, kg/m2 21.3±2.7 22.5±3.2　　 23.3±3.4　　 23.8±3.5　　 24.1±3.6　　 <0.001
Current smoking, % 18.5 16.6 18.6 18.9 22.6 0.11
Current drinking, % 44.1 46.3 48.4 51.2 54.1 <0.001
Regular exercise, % 9.2 13.3 11.6 14.9 12.0 0.04
All values are given as the mean ± SD or as a percentage. HBP, home blood pressure; HDL, high-density lipoprotein.

repeated measurements of morning and evening HBP for
each individual. All statistical analyses were performed
using the SAS program package version 9.3 (SAS Institute
Inc., Cary, NC, USA). P values <0.05 were considered
statistically significant.
Ethical Considerations
The study protocol was approved by Kyushu University
Institutional Review Board for Clinical Research, and the
procedures followed were in accordance with national
guidelines. Written informed consent was given by all the
subjects.
Results
For the total subjects, the mean value ± standard deviation
of morning HBP, evening HBP, and clinical BP at the health
examination was 132±18/77±10 mmHg, 124±16/70±9 mmHg,
and 131±19/79±11 mmHg, respectively. The mean values
of morning HBP were significantly higher than those of
evening HBP (both P<0.001). Both morning and eve-
ning HBPs were significantly correlated with clinical BP
(Pearson’s correlation coefficient: 0.64 between morning
systolic HBP and clinical systolic BP; 0.62 for evening
systolic HBP and clinical systolic BP; both P<0.001).
The clinical characteristics of the subjects according to
the levels of morning HBP and evening HBP are summa-
rized in Table 1 and Table S1, respectively. Subjects with
higher morning HBP levels were older and more likely to
be male. The mean values of BMI increased significantly
with increasing morning HBP levels, whereas the mean
values of HDL-cholesterol decreased significantly. The
frequencies of subjects with antihypertensive medication,
diabetes, lipid-lowering medication, current drinking, and
regular exercise increased significantly with increasing
morning HBP levels. Similar associations were observed
for evening HBP levels except for current smoking and
regular exercise: subjects with higher evening HBP levels
were more likely to be smokers and had no significant
association with the frequency of regular exercise.
Table 2 demonstrates geometric averages of mean and
maximum IMT according to the levels of morning or eve-
ning HBP. The age- and sex-adjusted geometric average of
mean IMT increased significantly and progressively with
increasing morning HBP levels (optimal: 0.67 mm; normal:
0.69 mm; high normal: 0.72 mm; grade 1 hypertension:
0.74 mm; grade 2+3 hypertension: 0.76 mm; P<0.001 for
trend) or evening HBP levels (optimal: 0.68 mm; normal:
0.71 mm; high normal: 0.73 mm; grade 1 hypertension:
0.76 mm; grade 2+3 hypertension: 0.78 mm; P<0.001 for
trend). These associations were substantially unchanged
even after adjustment for other cardiovascular risk factors,
namely, antihypertensive medication, diabetes, total and
HDL cholesterols, lipid-lowering medication, BMI, cur-
rent smoking, current drinking, and regular exercise. When
we examined the association of each morning and evening
HBP with the geometric average of maximum IMT, a sig-
nificant linear relation was observed between morning or
evening HBP and maximum IMT. The associations of
evening HBP with mean and maximum IMT were stron-
ger than those of morning HBP (both P for heterogeneity
<0.05).
We also estimated the prevalence and odds ratios for
carotid wall thickening (defined as maximum IMT >1.0 mm)
according to each HBP level (Table 3). The age- and sex-
adjusted prevalence of carotid wall thickening was sig-
nificantly increased in subjects with higher HBP levels
compared with those with optimal HBP levels in the morn-
ing. The multivariable-adjusted odds ratios (95% CIs) for
carotid wall thickening were 0.92 (0.69–1.23) for normal,
1.33 (1.00–1.76) for high normal, 1.46 (1.11–1.92) for grade
1 hypertension, and 1.67 (1.19–2.35) for grade 2+3 hyper-
tension, compared with the optimal level as a reference (P
for trend <0.001). A significant association was also
observed for evening HBP levels (multivariable-adjusted
odds ratio [95% CI]: 1.37 [1.09–1.72], 1.46 [1.13–1.87], 1.79
[1.37–2.35], and 3.14 [1.92–5.33], respectively; P<0.001 for
trend), indicating that both morning and evening HBP
levels were significantly associated with carotid wall thick-
ening independent of other cardiovascular risk factors.

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1650 SAKATA S et al.

Table 2.  Geometric Averages of Mean and Maximum IMT According to Morning or Evening HBP Levels
HBP level
P for P for
Grade 1 Grade 2+3 trend heterogeneity‡
Optimal Normal High normal
hypertension hypertension
Mean IMT
  Morning HBP
    No. of participants 518 458 587 891 407
    Age- and sex-adjusted 0.67 0.69 0.72 0.74 0.76 <0.001
geometric average (95% CI) (0.66–0.68) (0.69–0.70)* (0.71–0.73)* (0.73–0.74)* (0.75–0.77)*
    Multivariable-adjusted 0.68 0.70 0.72 0.74 0.76 <0.001 0.005
geometric average (95% CI)† (0.67–0.69) (0.69–0.71)* (0.71–0.73)* (0.73–0.74)* (0.75–0.77)*
  Evening HBP
    No. of participants 845 725 593 565 128
    
Age- and sex-adjusted 0.68 0.71 0.73 0.76 0.78 <0.001
geometric average (95% CI) (0.67–0.69) (0.70–0.72)* (0.72–0.74)* (0.75–0.77)* (0.76–0.80)*
    Multivariable-adjusted 0.69 0.71 0.73 0.75 0.78 <0.001
geometric average (95% CI)† (0.68–0.69) (0.70–0.72)* (0.72–0.74)* (0.74–0.76)* (0.76–0.80)*
Maximum IMT
  Morning HBP
    No. of participants 518 458 587 891 407
    Age- and sex-adjusted 1.14 1.13 1.20 1.25 1.31 <0.001
geometric average (95% CI) (1.11–1.18) (1.09–1.16) (1.17–1.24)* (1.22–1.28)* (1.26–1.35)*
    Multivariable-adjusted 1.15 1.14 1.20 1.25 1.29 <0.001 0.04　　
geometric average (95% CI)† (1.11–1.19) (1.10–1.18) (1.17–1.23) (1.22–1.28)* (1.25–1.34)*
  Evening HBP
    No. of participants 845 725 593 565 128
    Age- and sex-adjusted 1.14 1.18 1.22 1.30 1.40 <0.001
geometric average (95% CI) (1.11–1.17) (1.15–1.21)* (1.18–1.25)* (1.26–1.34)* (1.32–1.49)*
    Multivariable-adjusted 1.15 1.19 1.22 1.28 1.38 <0.001
geometric average (95% CI)† (1.12–1.18) (1.16–1.22) (1.19–1.26)* (1.25–1.32)* (1.30–1.47)*
*P<0.05 vs optimal level. †Adjusted for age, sex, antihypertensive medication, diabetes, total cholesterol, HDL cholesterol, lipid-lowering medi-
cation, body mass index, current smoking, current drinking, and regular exercise. ‡Heterogeneity for multivariable-adjusted geometric aver-
ages. CI, confidence interval; IMT, intima-media thickness. Other abbreviations as in Table 1.

Table 3.  Odds Ratios for Carotid Wall Thickening According to Morning or Evening HBP Level
HBP level
P for P for
Grade 1 Grade 2+3 trend heterogeneity‡
Optimal Normal High normal
hypertension hypertension
Morning HBP
   No. of cases/participants 86/513 149/458 264/587 489/891 270/407
  Age- and sex-adjusted 46.4 49.1　 58.2* 60.0* 65.2* <0.001
prevalence, %
  Age- and sex-adjusted 1 (Ref.) 0.95 1.45 1.62 1.88 <0.001
OR (95% CI) (0.72–1.26) (1.10–1.89) (1.25–2.09) (1.37–2.59)
  Multivariable-adjusted 1 (Ref.) 0.92 1.33 1.46 1.67 <0.001 0.02
OR (95% CI)† (0.69–1.23) (1.00–1.76) (1.11–1.92) (1.19–2.35)
Evening HBP
   No. of cases/participants 220/845 289/725 302/593 354/565 93/128
  Age- and sex-adjusted 47.5 57.0* 57.7* 63.4* 79.8* <0.001
prevalence, %
  Age- and sex-adjusted 1 (Ref.) 1.44 1.58 2.05 3.47 <0.001
OR (95% CI) (1.15–1.79) (1.24–2.00) (1.60–2.62) (2.11–5.69)
  Multivariable-adjusted 1 (Ref.) 1.37 1.46 1.79 3.14 <0.001
OR (95% CI)† (1.09–1.72) (1.13–1.87) (1.37–2.35) (1.92–5.33)
Carotid wall thickening was defined as maximum IMT >1.0 mm. *P<0.05 vs. optimal level. †Adjusted for age, sex, antihypertensive medication,
diabetes, total cholesterol, HDL cholesterol, lipid-lowering medication, body mass index, current smoking, current drinking, and regular exer-
cise. ‡Heterogeneity for multivariable-adjusted ORs. OR, odds ratio. Other abbreviations as in Tables 1,2.

Evening HBP was more strongly associated with carotid thickening defined as maximum IMT >1.5 mm (both P for
wall thickening than was morning HBP (P for heterogene- trend <0.001), but no evidence of heterogeneity between
ity=0.02). Increased morning and evening HBP levels were morning and evening HBPs was observed (P for heteroge-
also significantly associated with advanced carotid wall neity=0.55) (Table S2).

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Home BP and Atherosclerosis 1651

We conducted subgroup analyses stratified by the status

of antihypertensive medication (Tables S3,S4). The multi-
variable-adjusted geometric averages of the mean and
maximum IMT were higher in subjects with antihyperten-
sive medication than in those without, but increased sig-
nificantly and linearly with increasing morning or evening
HBP levels both in the subgroups of subjects with and
without antihypertensive medication (all P for heterogene-
ity >0.10). We also performed subgroup analyses stratified
by drinking status (Tables S5,S6). Regardless of drinking
status, there were significant associations of morning and
evening HBP levels with the geometric averages of mean
and maximum IMT, without any evidence of heterogeneity
between subgroups (all P for heterogeneity >0.05).
Next, we examined geometric averages of mean and
maximum IMT according to 4 BP groups: normotension,
isolated morning hypertension, isolated evening hyperten-
sion, and sustained hypertension (Figure; Table S7). The
multivariable-adjusted geometric average of the mean
IMT increased significantly in subjects with isolated morn-
ing hypertension, isolated evening hypertension, and sus-
tained hypertension compared with normotensive subjects.
For maximum IMT, similar associations were observed;
however, there was no significant increase in isolated eve-
ning hypertension, probably because of the relative small
number of subjects with isolated evening hypertension. In
the subgroup analyses stratified by antihypertensive medi-
cation status, there was no evidence of heterogeneity in the
association of the 4 BP groups with the mean and maxi-
mum IMT between the groups of antihypertensive medica-
tion status (both P for heterogeneity >0.4), although some
P values in the groups of isolated morning hypertension
and isolated evening hypertension did not reach the level
of statistical significance (Table S8). When we combined
the subjects with isolated morning hypertension and iso-
lated evening hypertension, subjects with either isolated
morning or evening hypertension had a significantly higher
mean and maximum IMT than those with normotension
(Table S9).
Figure.  Multivariable-adjusted geometric average of (A)
In addition, we performed a sensitivity analysis after mean and (B) maximum intima-media thickness according to
changing the cutoff value of evening HBP from 135/75 to blood pressure categories. *P<0.05 vs. normotension. Values
126/76 mmHg to correct for the imbalance in the number were adjusted for age, sex, antihypertensive medication, dia-
of subjects with isolated evening hypertension. As a conse- betes, total cholesterol, high-density lipoprotein cholesterol,
quence, the average mean IMT and maximum IMT in lipid-lowering medication, body mass index, current smoking,
subjects with isolated evening hypertension became lower, current drinking, and regular exercise. Whiskers indicate 95%
confidence intervals.
but the findings were not altered substantially (Table S10).
There was also no significant heterogeneity in the associa-
tion between antihypertensive medication status after
changing the cutoff value for evening HBP (both P for related to carotid atherosclerosis. However, there are lim-
heterogeneity >0.05) (Table S11) ited studies addressing the association of morning and
evening HBP separately with clinical or subclinical cardio-
vascular disease, especially in general populations. The
Discussion J-HOP Study,27 which evaluated outpatients with at least
The present study demonstrated that increased morning 1 cardiovascular risk factor, showed that higher morning
and evening HBP was significantly associated with the and evening HBP levels were significantly linked with
presence of carotid atherosclerosis in a general Japanese greater IMT, but the significant association remained only
population. It is noteworthy that these associations were for morning HBP after adjusting for confounding factors.
unchanged by the use of antihypertensive medication or In the present study, evening HBP as well as morning HBP
drinking status. The findings from this study are expected was clearly associated with carotid wall thickening. The
to show the importance of BP control in both the morning discrepancy in the findings between the studies may be
and the evening. attributable to the difference in study populations. Patients
A few epidemiological studies in Japan19,24 and Finland16 with cardiovascular risk factors are more likely to have
have provided consistent findings that higher HBP is sig- increased variability in evening BP, which tends towards a
nificantly associated with greater IMT despite differences non-significant association, caused by insufficient duration
in study populations. This suggests that mean HBP is closely of the action of antihypertensive medications28 and impair-

Circulation Journal  Vol.81, November 2017

1652
ment of baroreflex or autonomic dysfunction29–31 than gen-
eral populations. With regard to clinical cardiovascular
events, 2 population-based prospective cohort studies32,33
have shown that both morning HBP and evening HBP
have significant and equal predictive abilities for future
stroke or cardiovascular events. All this evidence indicates
the importance of assessing both morning and evening BP
to prevent future risks of cardiovascular disease.
The present study demonstrated that morning hyperten-
sion, which was hypertension observed in the morning
only, was significantly linked with greater IMT in this
general population. Several studies conducted in hyperten-
sive patients have reported that morning hypertension
has a strong association with target organ damage8,9,34 and
cardiovascular events.35,36 However, there are few previous
studies that have examined this issue in general popula-
tions.32 Morning hypertension is considered to reflect
inadequate BP control during night (e.g., via insufficient
duration of action of antihypertensive drugs) and increased
activities of neurohumoral factors, such as the sympathetic
nervous system and the renin-angiotensin system in the
morning, which promotes progression of arterial dam-
age.10,11,28 Therefore, controlling morning BP is important
for the prevention of atherosclerotic disease.
Evening BP has greater variability, affected more by
antihypertensive mediations, daily customs (e.g., bathing
and evening drink) and activities than morning BP.12
Therefore, morning BP may be considered as a more useful
indicator of target organ disease than evening BP in clini-
cal practice. In the current analysis, however, evening
hypertension, defined as hypertension in the evening only,
was clearly associated with mean IMT, just as with morn-
ing hypertension. No prior population-based investigation
has evaluated this issue for carotid atherosclerosis to date.
A prospective study of a general Japanese population32
supportively demonstrated that subjects with evening
hypertension tended towards having a higher risk of stroke
compared with normotensive subjects, though this associa-
tion was not statistically significant. This finding, together
with ours, suggests that higher evening BP itself contrib-
utes to the atherosclerotic process. Moreover, in the pres-
ent study, evening HBP showed a significantly greater
association with carotid atherosclerosis than morning
HBP, a finding that was probably attributable to the fact
that the morning and evening HBP levels were higher in
each of the high normal and hypertension categories deter-
mined on evening HBP than in the corresponding catego-
ries defined on morning HBP (Table 1,S1). This may
suggest that evening HBP is a better predictor of athero-
sclerosis than morning HBP, but the clinical significance of
evening hypertension remains to be investigated.
Study Limitations
First, we were not able to determine a causal association of
morning and evening HBP with IMT because of the cross-
sectional study design. Second, several laboratory techni-
cians measured maximum IMT manually, therefore there
is the possibility that the association between HBP and
maximum IMT observed in the present study was weaker
than the true association. However, this limitation is unlikely
to alter the conclusions of the present analysis, because
similar results were obtained for mean IMT, which was
estimated automatically using a computer-assisted mea-
surement system. Finally, we could not exclude the possi-
bility that residual confoundings still exist in the association.
Circulation Journal  Vol.81, November 2017
SAKATA S et al.
Conclusions
To the best of our knowledge, this is the first report to
demonstrate the association of both morning and evening
HBP with IMT in a general population. Both morning and
evening HBP provided equally valuable information for
target organ damage, therefore physicians should use both
HBP measurements as indicators in the management of
hypertension. Further longitudinal study addressing the
influence of morning and evening HBPs on cardiovascular
risk is warranted to elucidate this issue.
Acknowledgments
We thank the staff of Division of Health and Welfare of Hisayama for
their cooperation in this study.
Sources of Funding
This study was supported in part by Grants-in-Aid for Scientific
Research (A) (16H02644 and 16H02692), (B) (16H05850), and (C)
(26350895, 26460748, 15K09267, 15K08738, 15K09835, and 16K09244)
from the Ministry of Education, Culture, Sports, Science and Technology
of Japan; by Health and Labour Sciences Research Grants of the
Ministry of Health, Labour and Welfare of Japan (H25-Junkankitou
[Seishuu]-Sitei-022, H26-Junkankitou [Seisaku]-Ippan-001, and H27-
Shokuhin-[Sitei]-017); and by the Japan Agency for Medical Research
and Development (AMED) (16dk0207025h0001, 16ek0210042h0002,
and 16gm0610007h0204 (CREST)).
Conflict of Interest / Disclosures
None.
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Supplementary Files
Supplementary File 1
Figure S1.   Correlation of morning and evening home blood pres-
sures.
Table S1.   Clinical characteristics of participants according to eve-
ning HBP levels
Table S2.   ORs for advanced carotid wall thickening according to
morning or evening HBP levels
Table S3.   Geometric averages of mean IMT according to morn-
ing or evening HBP levels among subjects with and without
antihypertensive medication
Table S4.  Geometric averages of maximum IMT according to
morning or evening HBP levels among subjects with and without
antihypertensive medication
Table S5.   Geometric averages of mean IMT according to morn-
ing or evening HBP levels among subjects stratified by drinking
status
Table S6.  Geometric averages of maximum IMT according to
morning or evening HBP levels among subjects stratified by
drinking status
Table S7.  Geometric averages of mean and maximum IMT
according to HBP categories
Table S8.  Geometric averages of mean and maximum IMT
according to HBP categories among subjects with and without
antihypertensive medication
Table S9.  Geometric averages of mean and maximum IMT
according to HBP categories
Table S10.  Geometric averages of mean and maximum IMT
according to HBP categories (different cutoff values for morning
and evening)
Table S11.  Geometric averages of mean and maximum IMT
according to HBP categories among subjects with and without
antihypertensive medication (different cutoff values for morning
and evening)
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-16-1306