Circadian rhythm of blood pressure is transformed from a

Journal of Human Hypertension (2002) 16, 193–197
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ORIGINAL ARTICLE
Circadian rhythm of blood pressure is
transformed from a dipper to a non-dipper
pattern in shift workers with hypertension
T Kitamura, K Onishi, K Dohi, T Okinaka, M Ito, N Isaka and T Nakano
The First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
Shift workers make great use of health care services
because they are associated with increased cardiovascular morbidity and mortality. Whether the circadian
rhythm of blood pressure rapidly adapts to shift work is
controversial. It is unknown if shift work has adverse
effects on blood pressure in patients with hypertension.
To evaluate the effects of shift work, we examined 12
male shift workers with untreated hypertension aged
53.6 ± 2.5 years. Twenty-four hour ambulatory blood
pressure monitoring was performed three times as
follows: the last day of a 4-day period of day shifts
(09.00 to 21.00), the first day of a 4-day period of night
shifts (21.00 to 09.00), and the fourth day of night shifts
(21.00 to 09.00). Blood pressure at night-time dropped
significantly in the day-shift workers, showing a dipper
pattern. Average differences in blood pressure in the
sleep-wake cycle were decreased by 8.5% at the beginning of night shift work showing a non-dipper pattern.
After 4 days the pattern was completely reversed to a
dipper pattern. The results indicate that the circadian
blood pressure pattern is changed from a dipper to a
non-dipper pattern on the first day of the night shift and
reverses to a dipper pattern within a few days. We
suggest that night shift work may have unfavourable
effects on blood pressure in patients with hypertension.
Journal of Human Hypertension (2002) 16, 193–197. DOI:
10.1038/sj/jhh/1001328
Keywords: blood pressure; circadian rhythm; shift work; non-dipper
Introduction
Biological rhythms are an essential component of
homoeostasis: ‘everything is rhythmic unless proved
otherwise’. Most rhythms are driven by an internal
biological clock located in the hypothalamic suprachiasmatic nucleus and can be synchronized by
external signals such as light–dark cycles.1
In general, blood pressure (BP) is also modulated
in a circadian rhythm: over a 24-h cycle. The dipper
pattern shows high BP in the daytime and low BP at
night. It has been suggested that the rhythm closely
follows the sleep-wakefulness cycle2,3 and changes
in BP are merely a result of differences in physical
activity;4 thus, the circadian BP rhythm is largely
independent of internal circadian rhythm.3 However, some abnormal conditions, such as autonomic
failure5 or small lacunar infarcts,6 show non-dipper
BP patterns independent of the sleep-wakefulness
cycle. Non-dippers, in whom nocturnal BP
decreases less than 10%, have been proposed as a
subgroup associated with increased frequency of
damage to all target organs (brain, heart, and kidney)
and a poorer prognosis for cardiovascular events.7–9
A recent study on shift workers suggests that
night-shift workers are more likely to be classified
as non-dippers than are day workers.10 However, it
is not clear if a dipper pattern in hypertensive shift
workers would change to a non-dipper pattern if the
workers changed from a day shift to a night shift.
Therefore, we compared the diurnal BP in 12-h
shift workers (completely reversed day and night)
on (1) the day shift (DS), (2) the first day of the night
shift (NS I), and (3) the fourth day of the night shift
(NS II). To avoid confounding factors, untreated,
mild hypertensive 12-h shift workers who worked
at jobs with little physiological and psychological
variety were chosen from the same gender group in
a narrow age range.
Subjects and methods
Subjects
Correspondence: T Kitamura, MD, PhD, The First Department of
Internal Medicine, Mie University School of Medicine, 2–174,
Edobashi, Tsu, 514 –8507, Japan
E-mail: ted얀clin.medic.mie.u.ac.jp.
Received 27 June 2001; revised and accepted 17 October 2001
We studied 12 hypertensive men aged 50 to 57 years
(mean 53.6 ± 2.5 years), with mean office systolic BP
of ⬎140 mm Hg and/or mean office diastolic BP of
⬎90 mm Hg (average for each patient on three or
Blood pressure in shift workers
T Kitamura et al
194
more occasions). The office BP was measured in the
sitting position using standard cuff methods.
Throughout the period preceding each monitoring
session, the subject’s pattern of activity, such as
work, leisure, and sleep was adjusted to that on the
monitoring day. The subjects are employees of a factory that assembles and tests memory devices, and
their physical and psychological work activities
consisted of takes with little variety.
None of the patients had received any antihypertensive medication for at least for 14 days before the
study. The results of all physical and laboratory
examinations (these included blood and urine tests,
chest X-ray, and ECG at rest) were normal or consistent with World Health Organization Stage I. We
excluded from this study those with renal failure
and/or hepatic damage (serum creatinine level
⬎130 mmol/l, urea nitrogen level ⬎10.7 mmol/l,
positive glucosuria and proteinurea detected by
multistix, and aspartate aminotransferase or alanine
aminotransferase level ⬎40 IU/l). Also excluded
were those with obvious present illness or with a
past history of coronary artery disease, stroke
including transient ischaemic attacks, congestive
heart failure, arrhythmia, or malignancy. Those with
possible diabetes mellitus (fasting glucose level
⬎5.5 mmol/l or haemoglobin AIC ⬎ 5.8%) were also
excluded from this study.
Protocol
Subjects who registered in this study had the same
working schedule; 4-day period of day shift, 2 days
off, and 4-day period of night shift. Twenty-four
hour automatic, non-invasive BP monitoring was
performed three times on each subject on: (1) the
last day of a 4-day period of day shifts (DS), (2) the
first day of a 4-day period of night shifts (NS I), and
(3) the last day of the 4 days of night shifts (NS II).
The schedule on the monitoring days was as follows: DS indicates a working time is from 9.00 am
to 9.00 pm and monitoring began at 9.00 am; NSI
and NSII indicate a working time from 9.00 pm to
9.00 am and monitoring began at 10.00 am. During
working time, the room temperature, noise, and
light illumination were kept constant.
The daily life of the subjects was restricted. Bath,
shower, sauna, or physical exercise other than walking could be taken. No alcohol was consumed during the 24-h monitoring period. The subjects were
instructed to remain motionless and to hold their
arm in a relaxed position during each reading.
The subjects reported the exact time spent both
asleep and at work in a trial diary. Based on this
information, the average systolic and diastolic BP,
as well as standard deviation (s.d.) were calculated
from all BP readings during daytime awake hours
and night time sleeping hours for DS, and daytime
sleeping hours and night time awake hours for NS.
Journal of Human Hypertension
24-h ambulatory BP monitoring
Noninvasive ambulatory BP monitoring was performed using automatic ambulatory BP monitoring (ESH531, Terumo Co. Ltd, Tokyo, Japan), which
recorded BP every 60 min for 24 h. The accuracy of
this device has been previously validated.11 The
device displays primarily the values obtained by the
Korotokoff method (K-method). It can be used for
BP measurement by the microphone method whose
values satisfy the accuracy criteria of the American
Association of Medical Instruments and accord with
a grade of A in the accuracy criteria of the British
Hypertension Society (BHS).
If the Korotokoff sound (K-sound) signals are not
strong enough or are obliterated by excessive noise,
the values obtained by the cuff-oscillometric method
(O-method) are displayed automatically instead.
The O-method accords with Grade B in the BHS
accuracy criteria. When noises (mainly caused by
body movement) are detected during deflation, the
measurement is repeated.
Awake and asleep times were evaluated from the
diaries of the subjects. The body mass index was calculated as weight (kg)/height (m2). The mean arterial
pressure (MAP) was calculated as diastolic BP plus
1/3 of pulse BP. %BP fall was calculated as the
(awake BP–sleep BP)/awake BP ratio (%).
This study was approved by the Research Committee of Mie University School of Medicine and
informed consent was obtained from each subject.
Statistical analysis
All data are expressed as mean ± standard deviation.
ANOVA was used to assess the differences among
subgroups defined according to work shift and
sleep/awake periods. Comparison between groups
(DS, NS I, and NS II) was first performed by analysis
of variance, and then pairwise comparison was performed using the unpaired t-test with the Bonferroni
procedure if the F-test showed an overall difference.12 A P-value ⬍0.05 (two-tailed probability) was
considered statistically significant.
Results
Table 1 shows the characteristics of the 12 shift
workers. All subjects were men, current smokers,
and had participated in shift work within the 6
months before the study began.
Figure 1 shows the average of hourly mean MAP
values of the 12 subjects during DS, NS I, and NS
II. The DS subjects showed a typical dipper pattern
with a drop in BP at night. This BP pattern was
reversed in the night shifts, because night-shift
workers need to wake up when they should be
asleep and need to sleep when they would normally
be awake. The NS II subjects showed a dipper pattern with a drop in BP in the daytime period. The
fluctuation of diurnal BP in NSI was relatively
smaller than NS II.
Blood pressure in shift workers
T Kitamura et al
195
Table 1 Characteristics of hypertensive shift workers
Number
Age
Sex
Body mass index
Experimental period of 12-h
shift work
Office BP
Systolic BP
Diastolic BP
Antihypertensive medication
Hours of sleep
DS
NS I
NS II
12
53.6 ± 2.5 years
Male
23.6 ± 2.0 kg/m2
⬍6 months
148.5 ± 8.7 mm Hg
93.2 ± 8.7 mm Hg
None
8.7 ± 1.1 h

7.3 ± 0.9 h

6.9 ± 1.6 h
*
NS

*

*P ⬍ 0.05 vs DS. Mean (s.d.) values are shown. BP = blood pressure; DS = day shift period; NS I = first day of night-shift period,
NS II = fourth day of night-shift period.
Figure 2 Proportion of %BP fall in sleep-wake cycle according
to work shift. %BP fall was calculated as the (awake BP − sleep
BP)/wake BP ratio (%). Vertical bar represents mean ± s.e.m.
Figure 1 Circadian diurnal rhythms of MAP in 12 shift workers.
䊊, DS periods; 䊐, NS I periods; and 왕, NS II periods. Vertical
bar represents mean ± s.e.m.
In the sleep-wake cycle, MAP declined by
16.0 ± 3.1% in DS and 13.4 ± 5.6% in NS II indicating a dipper pattern. However, MAP in NS I
declined by only 8.5 ± 8.5% indicating a non-dipper
pattern (Figure 2). These results suggest that the circadian BP rhythm changed from a dipper pattern to
a non-dipper pattern on the first day of night shifts
and reversed to a dipper pattern on the fourth day
of night shifts.
During sleep, MAP in NS I were significantly
higher than DS and tended to be higher than NS II;
there were no significant differences between DS
and NS II (Figure 3). According to the diaries, the
duration of sleep was the longest and the quality of
sleep was the best in DS. There was no significant
difference between sleep duration or quality
assessed by the diaries and sleeping BP level by the
analysis of individual shift workers.
Discussion
In this study we have evaluated the circadian BP
variations in mild-hypertensive shift workers using
ambulatory blood pressure measurement. Our main
finding is that working on the night shift alters the
normal diurnal rhythm of BP.
Figure 3 Proportion of average of MAP during sleep period
according to work shift. Vertical bar represents mean ± s.e.m.
Our study was conducted on 12-h shift workers.
To the best of our knowledge, it is the first report
that in hypertensive patients the circadian variation
of BP changed from a dipper to a non-dipper pattern
on the first day of the night shift and changed back
to a dipper pattern after a few days.
Generally, it is well known that BP fluctuates over
a 24-h period. It has been suggested that this fluctuation is dependent upon three factors: complex
internal physiologic mechanisms, external stresses,
and the subject’s own circadian rhythm. In the
present study, the circadian rhythm of the day-shift
workers suggests that these factors are operative,
resulting in high BP during daytime work and low
BP during sleep at night, indicating a dipper pattern.
Journal of Human Hypertension
Blood pressure in shift workers
T Kitamura et al
196
However, working the night shift alters the normal
diurnal rhythm of BP. The circadian variation of BP
on the first day of the night shift showed that the
fluctuation of change in BP was small (less than
10%) during the day due to increased BP during
sleep and decreased BP during the awake period,
thus indicating a non-dipper pattern. Thus, we have
shown that the diurnal BP changes from a dipper to
a non-dipper pattern on the first day of the night
shift and reverses to a dipper pattern after a few
days. The reason for this is not known. The complex
internal physiologic mechanisms and external
stresses of shift work might affect the diurnal
rhythm of BP by the reversal of the awake and
asleep periods.
Yamasaki et al10 suggested that more night shift
workers than day workers are as non-dippers, probably because the quality of sleep was impaired by
shift work, and sleep deprivation may induce high
nocturnal BP.10,13 Unfortunately, they did not obtain
reports of sleep quality from their subjects. In our
study, the quality of sleep did not differ between NS
I and NS II, although, according to their diaries,
night-shift work impaired the quality of sleep in
comparison with day-shift work. There was no significant difference between sleep duration or quality
assessed by the diaries and sleeping BP level by the
analysis of individual shift workers. We speculate
the reason for the different BP patterns between NS
I and NS II (Figure 1), that the endogenous factors
including a poorly understood ‘internal biological
clock’, as well as other biological parameters such
as body temperature, growth hormone secretion, or
urinary excretion of electrolytes2,3 might affect the
circadian rhythm of BP.
In contrast to our results, some studies on shift
workers have shown an immediate adaptation to a
shifted phase of activity and sleep,2–4 indicating a
dipper pattern on all the shifts. The difference may
be due to the use of different subject groups. Their
studies did not completely reverse day and night
periods; they included not only 12-h shifts but a variety of work shifts (8-h shifts, etc). We used only 12h shift workers to limit the alteration of circadian
time structure of BP caused by various night-shift
schedules. Differences in the timing of data collection may have caused the different results.14 Variation in physiological and psychological activities
may also have affected the circadian variation of BP
in the earlier studies. Our subjects assembled and
tested memory devices that depend on automatic
technology which minimises variation in physiological and psychological activities. Furthermore,
our subjects were selected for uniformity: they were
all of the same gender and in a narrow age range.15,16
Clinical implication
Shift workers need to wake up when they should be
asleep and need to sleep when they would normally
be awake. They have a higher incidence of poorer
Journal of Human Hypertension
sleep.17 Some studies have demonstrated that shift
work is associated with increased cardiovascular
morbidity and mortality.18–20 Recently, Furlan et al21
reported that a shift schedule of work might be associated with modification of the cardiac autonomic
profile. Although the reason is not known, high BP
leading to increased sympathetic nervous activity
due to sleep disturbance22,23 may be partly responsible.10,13 In this study, we found an increased BP in
subjects on the first day of the night shift. It may be
during the transition period that they are most likely
to be at risk of events.
Limitations
It was difficult to completely regulate the same lifestyle of each worker, especially the quality of sleep.
To avoid confounding factors as much as possible,
the daily life of the subjects were restricted. The subjects all work in the same factory that assembles and
tests memory devices and have minimal variety in
their physical and psychological activities. During
working hours, room temperature, noise, and light
illumination are kept constant. Bath, shower, sauna,
or physical exercise other than walking could be
taken. No alcohol was consumed during the 24-h
monitoring period. There may be differences in circadian variation between the experienced and inexperienced shift workers.
Any procedure producing mild discomfort (such
as inflation of a BP cuff) may cause stimulation of
the orienting (or arousal) reflex leading to some
increases in BP. Although over a period of time the
response to this stimulation would become attenuated which may decrease BP, our result in this paper
showed the higher BP during sleep on the second or
third recording for each subjects (night shifts) than
on the first recording (day shift).
Moderate smokers were entered in this study.
Although it has been reported that smoking might
influence daytime BP, the effect of smoking seems
to be more relevant in heavy smokers, particularly
for systolic BP, and less important in moderate
smokers.24
Conclusion
We conclude that the circadian variation of BP
changed from a dipper to a non-dipper pattern on
the first day of the night shift and reversed to a dipper pattern within a few days. BP during sleep in
the first day of the night shift was higher than on
the other days.
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