Circadian rhythm of blood pressure is transformed from a dipper to a non-dipper pattern in shift workers with hypertension

(2002) 16, 193 197 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh 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. (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 cycle 2,3 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 failure 5 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 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: ted clin.medic.mie.u.ac.jp. Received 27 June 2001; revised and accepted 17 October 2001 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 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

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 A IC 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. 24-h ambulatory BP monitoring Noninvasive ambulatory BP monitoring was performed using automatic ambulatory BP monitoring (ES- H531, 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 (m 2 ). 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.

Table 1 Characteristics of hypertensive shift workers 195 Number 12 Age 53.6 ± 2.5 years Sex Male Body mass index 23.6 ± 2.0 kg/m 2 Experimental period of 12-h 6 months shift work Office BP Systolic BP Diastolic BP Antihypertensive medication 148.5 ± 8.7 mm Hg 93.2 ± 8.7 mm Hg None Hours of sleep DS 8.7 ± 1.1 h * NS I 7.3 ± 0.9 h * NS NS II 6.9 ± 1.6 h *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., DS periods;, NS I periods; and, 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.

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 al 10 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 electrolytes 2,3 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 12- h 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 sleep. 17 Some studies have demonstrated that shift work is associated with increased cardiovascular morbidity and mortality. 18 20 Recently, Furlan et al 21 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 disturbance 22,23 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. 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