Sleep restriction progress to cardiac autonomic imbalance

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 31 May 2017

Abstract

Previous studies have shown that night shift work is thought to be a risk factor for cardiovascular disease and inadequate sleep is a common feature of night shift work. Since it’s more difficult to maintain adequate sleep duration among night watchmen during their working schedule, hence the purpose of our present study was to investigate whether mental stress or fatigue over restricted sleep period in night shift, affects HRV, in order to elucidate on cardiac autonomic modulation among nigh watchmen. With the purpose of this, autonomic activity determined from the levels of the heart rate variability (HRV), and also measured, body mass index (BMI), body fat percentage from skin fold thickness (biceps, triceps, and sub-scapular, supra-iliac) among normal sleep watchmen) (n = 28) and restricted sleep watchmen (n = 28) at first (1st) day, fourth (4th) day and seventh (7th) day of restricted sleep period. We observed that among restricted sleep individuals, sleepiness was significant increase at 4th day and 7th day when compare to normal sleep individuals, and, there was significant increase in, mean NN, VLF, LF, LF(nu), LF/HF AND significant decrease in SDNN, RMSSD, TSP, HF, and HF(nu) at 4th and 7th day of restricted sleep period. In addition to, this variable was more significant increase on 7th day, when compare with 4th day. As well as there was significant negative correlation between LF(nu) and HF(nu) at subsequent 4th day [r (48) = −0.84; P = 0.01] and 7th day[r (48) = −0.95; P = 0.01] of restricted sleep period. However we didn’t observe any significant variation in BMI, and body fat percentage among restricted sleep individuals when compare to normal sleep individuals with in this restricted sleep periods. Hence we concluded that partial sleep loss may cause autonomic imbalance represented by increased sympathetic and decreased parasympathetic activity; as revealed by altered HRV indices observed in this study.

Keywords:

• Sleep restriction
• Autonomic balance
• BMI
• HRV

1 Introduction

Inadequate sleep is a common feature of shift work. Sleep loss during shift work is a growing problem in our modern society and may become a major threat for health and wellbeing in the near future and supposed to be a threat for cardiovascular disease (CVD).^1–5 Sleep loss may be affecting stress system which plays a critical role in this adaptation.⁶ Acute sleep loss may be associated with increased heart rate and blood pressure, and a shift of sympathovagal balance toward sympathetic dominance.^7,8

The heart rate variability (HRV) analysis is a non-invasive diagnostic technique, has been proposed for the study of autonomic nervous system.⁹ The heart rate (HR) is modulated by the combined effects of the sympathetic (SNS) and parasympathetic (PNS) nervous systems. Therefore, measurement of changes in HR (heart rate variability or HRV) provides information about cardiac autonomic functioning.¹⁰ Slower HRV rhythms (LF) specify increased sympathetic and/or lower vagal activity, whereas faster HRV rhythms (HF) SPECIFY lower sympathetic and/or increased vagal activity. ¹⁰ Hence, the variability in heart rate, (with reduced heart rate variation), has been proposed as an independent prognostic marker for an imbalance of normal cardiac autonomic control mechanisms.¹¹

HRV is measured using: time-domain, frequency (spectral)-domain, and geometrical analysis methods. In time-domain, SD index and low frequency spectra can reflect a combination of sympathetic and parasympathetic activity while rMSSD, pNN50 and high frequency spectra represent the conditions of parasympathetic activity.

Frequency domain method is analyzed by studying the power spectral density. It provides information about the power distribution across frequencies.⁹ The two key components are low-frequency band (LF) and high-frequency band (HF). LF is considered to be an indicator for sympathetic activity, in contradiction, HF is determined by vagal effect.⁹ The LF/HF ratio has been derived from these values to show sympathovagal balance.⁹

The sympathetic activation is considered to be the main mechanism involved in the development of cardiovascular diseases in sleep impairment.^12,13 The impairment of HRV parameters with an increased incidence of adverse cardiovascular and metabolic disorders in sleep loss has been acknowledged.^14–16 However, only limited studies have conveyed upon the dynamics of the autonomic nervous system during partial sleep loss or restricted sleep.^17–19

Thus, the purpose of our present study was to investigate whether mental stress or fatigue over restricted sleep period for the duration of night shift among nigh watchmen, affects HRV, in order to elucidate on cardiac autonomic modulation.

2 Methods

2.1 Ethics declaration

The study was approved by the local research advisory committee of People College of Medical Science and Research Center (PCMS/OD/2015/1056). The study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from each subject before the start of the study, and all evaluations were performed at completion of first (1st) day, fourth (4th) day and seventh (7th) day of restricted sleep period.

2.2 Study design

The study population consisted of 50 healthy good sleepers, night watch men ranging in age from 18 to 35 years and underwent a medical interview to ensure that they had a regular sleep/wake schedule. None of the subjects had cardiovascular complication such as hypertension, diabetes mellitus, and hyperlipidemia. The participants were divided into two groups.

• Group I-(Normal sleep) (n = 28) - Twenty-eight watchman working in day time and used to have normal sleep in night (≥8 h).

• Group II-(Restricted sleep) (n = 22) - Twenty-two watchman working in night time and used to have restricted sleep in night (≤3 h).

2.3 Protocol

2.3.1 Sleep schedule assessment

The participants were instructed to maintain a regular sleep–wake schedule and were monitored. No stimulant of any kind was allowed during the study. For the tests obtained in normal rested condition, instructed to participants to maintain normal sleep in night every day. In sleep restriction condition, participants were also instructed to sleep in night less than three hours (<3 h) for one week in their night shift schedule. All the participants were not allowed to sleep in day time. Participants slept at home and completed scheduled sleep diaries, regularly while at home, the duration of sleep was self-monitored. Total time in bed was recorded with a click button by the subject when getting into and out of bed. Participants reported less sleep during study duration which was also confirmed by monitors. After completion of one week study period, participants visited to the laboratory on the morning at 09:00 a.m for assessment. Each participant was tested after a normal sleep night and after a restricted sleep night in random order. The study was conducted in the department of physiology, peoples college of medical science and research center, Bhopal; India. All the measurement was assessed in the normal resting state, with abstinence from alcohol and caffeine at first (1st) day, fourth (4th) day and seventh (7th) day of restricted sleep period. All laboratory assessments were done in triplicate, at the end of study period.

The following clinical data were recorded: the Karolinska Sleepiness Scale (KSS),²⁰ body mass index (BMI)²¹ and the percentage of body fat²² was determined from the sum of the thickness of four skinfolds (biceps, triceps, suprailiac and subscapular) by using a Harpenden Skinfold Caliper (British Indicators, Burgess Hill, UK).

2.4 Measurement of HRV indices

To study the HRV, we performed 5-min of consecutive digitized electrocardiographic (ECG) signals recording after completion of restricted sleep periods at first (1st) day, fourth (4th) day and seventh (7th) day. All obtained beats (QRS complexes) were amplified further and reviewed on the analyzer screen to avoid any artificial labeling of the QRS complex. The analysis of HRV was performed by the Kubios HRV (version 1.1, Finland) software after research and correction of artifacts, in accordance with the guidelines issued by the European Society of Cardiology and The North American Society of Pacing and Electrophysiology in 1996.⁹ We analyzed in time-domain variables: mean NN was the mean of RR intervals of normal sinus beats (mean RR, ms), and RMSSD was the square root of the mean of the sum of the squares of differences between adjacent RR intervals. The standard deviation of the RR-intervals (SDNN, ms), and the root mean square of the difference between successive normal intervals (RMSSD, ms).

In frequency domain analysis, the total spectral power (TSP) was calculated for very-low frequency (VLF, 0.00330.04 Hz), low-frequency (LF, 0.040.15 Hz), and high-frequency bands (HF, 0.15 0.40 Hz). The LF/HF ratio was also included in the statistics. Normalized values of HF (nuHF) and LF (nuLF) bands had been re-calculated using the formulas of nuLFLF/HFLF and nuHFHF/HFLF.

3 Statistical analysis

Data are expressed as Mean ± Standard deviation (SD). All data were analyzed with the SPSS for windows statistical package (version 20.0, SPSS Institute Inc., Cary, North Carolina. Statistical significance between the different groups was determined by the independent student ʻt’ test and the significance level was fixed at p ≤ 0.05 (95% confidence intervals). Finally, Pearson correlation coefficient was used to find correlation between two variables.

4 Results

4.1 Effect of restricted sleep on sleepiness and BMI

The data are summarized in (Fig. 1) with mean ± SD. Among all normal and restricted sleep individuals, KSS score was comparable on 1st day of restricted sleep. However at subsequent on 4th day and 7th day of restricted sleep, there was significant increase in KSS score in restricted sleep individual when compare to normal sleep individuals indicating higher levels of sleepiness. In addition to, sleepiness level on 7th day was more significant increase, when compare with 4th day of restricted sleep period.

Fig. 1 Effect of restricted sleep on karolinska sleepiness scale (KSS), where ^* significance change (p ≤ 0.05) compared with normal sleep and ^# – significance change (p ≤ 0.05) compared with 4th day.

4.2 Effect of restricted sleep on BMI, skin fold and body fat percentage

The data are summarized in (Table 1) with mean ± SD. Among all normal and restricted sleep individuals, however, we didn’t observe any significant variation in BMI, skin fold (biceps, triceps, and sub-scapular, supra-iliac) and body fat percentage among restricted sleep individuals when compare to normal sleep individuals with in this restricted sleep periods.

Table 1 Effect of restricted sleep on body mass index (BMI), skin fold and body fat percentage, where ^* significance change (p ≤ 0.05) compared with normal sleep and ^# – significance change (p ≤ 0.05) compared with 4th day.

	1st Day	4th Day	7th day
Sleep time (h)
Normal sleep	8.5 ± 2.0	8.2 ± 1.5	8.3 ± 1.2
Restricted sleep	1.4 ± 0.9	1.3 ± 0.7	1.0 ± 0.8
BMI (kg/m^2)
Normal sleep	21.89 ± 8.24	22.52 ± 7.32	24.32 ± 5.64
Restricted sleep	22.45 ± 7.15	25.30 ± 6.56	27.83 ± 8.67
Biceps (mm)
Normal sleep	6.80 ± 0.68	6.70 ± 0.55	6.60 ± 0.47
Restricted sleep	6.65 ± 0.45	6.60 ± 0.40	6.75 ± 0.30
Triceps (mm)
Normal sleep	13.25 ± 2.40	14.23 ± 1.85	13.95 ± 1.60
Restricted sleep	13.80 ± 1.75	14.10 ± 1.50	14.50 ± 1.25
Sub-scapular (mm)
Normal sleep	12.70 ± 1.89	11.80 ± 2.10	12.25 ± 1.70
Restricted sleep	13.25 ± 1.70	12.60 ± 2.56	13.10 ± 1085
Supra-iliac (mm)
Normal sleep	15.45 ± 2.55	16.70 ± 1.40	15.20 ± 2.15
Restricted sleep	16.20 ± 1.90	15.80 ± 1.75	16.50 ± 1.80
Body fat percentage (mm)
Normal sleep	22.20 ± 3.15	23.17 ± 3.40	22.65 ± 3.20
Restricted sleep	21.80 ± 3.50	22.50 ± 3.75	23.30 ± 3.80

4.3 Effect of restricted sleep on time-domain variables

The data are summarized in (Table 2) with mean ± SD. The NN, SDNN and RMSSD were comparable in among all normal and restricted sleep individuals on 1st day and of restricted sleep. However at subsequent on 4th day and 7th day of restricted sleep period, NN was significantly increased and SDNN and RMSSD were significantly decreased in restricted sleep individuals when compare to normal sleep individuals. As well as, this variation was more significant change respectively on 7th day, when compare with 4th day of restricted sleep period.

Table 2 Effect of restricted sleep on time and frequency domain of HRV analysis. Where ^* significance change (p ≤ 0.05) compared with normal sleep and ^# – significance change (p ≤ 0.05) compared with 4th day.

	1st Day	4th Day	7th day
Time domain
Mean NN (ms)
Normal sleep	860 ± 182	875 ± 155	858 ± 167
Restricted sleep	893 ± 118	1375 ± 210^*	2046 ± 232^*
SDNN (ms)
Normal sleep	47.12 ± 3.85	45.28 ± 4.65	44.23 ± 5.74
Restricted sleep	46.85 ± 3.20	31.42 ± 7.30^*	14.25 ± 6.53^*
RMSSD (ms)
Normal sleep	39.20 ± 3.74	37.12 ± 4.85	36.84 ± 4.96
Restricted sleep	38.73 ± 3.20	23.38 ± 6.82^*	10.30 ± 3.64^*
Frequency domain
TSP (ms^2)
Normal sleep	3628 ± 380	3462 ± 236	3610 ± 250
Restricted sleep	3570 ± 296	2767 ± 326^*	1938 ± 215^*
VLF (ms^2)
Normal sleep	873 ± 95	838 ± 60	863 ± 73
Restricted sleep	885 ± 80	1237 ± 112^*	1749 ± 130^*
LF (ms^2)
Normal sleep	1067 ± 170	1039 ± 86	1096 ± 133
Restricted sleep	1123 ± 103	1482 ± 150^*	2123 ± 245^*
HF (ms^2)
Normal sleep	955 ± 120	915 ± 110	890 ± 105
Restricted sleep	876 ± 132	623 ± 104^*	260 ± 112^*
LF (nu)
Normal sleep	42.25 ± 6.53	41.85 ± 5.20	40.96 ± 5.75
Restricted sleep	43.67 ± 4.20	57.60 ± 7.13^*	80.70 ± 8.55^*
HF (nu)
Normal sleep	38.42 ± 3.80	36.50 ± 5.29	37.30 ± 4.20
Restricted sleep	37.28 ± 4.33	25.39 ± 4.80^*	10.64 ± 5.66^*
LF/HF
Normal sleep	1.05 ± 0.26	1.10 ± 0.13	1.08 ± 0.20
Restricted sleep	1.21 ± 0.30	2.37 ± 0.45^*	4.26 ± 0.63^*

* Significance change (p ≤ 0.05) compared with normal sleep.

4.4 Effect of restricted sleep on frequency domain variables

The data are summarized in (Table 2, Figs. 2 and 3) with mean ± SD. Among all normal and restricted sleep individuals, all frequency variable such as TSP, VLF, LF, HF, LF(nu), HF(nu) and LF/HF, were comparable on 1st day and of restricted sleep period. However at subsequent on 4th day and 7th day of restricted sleep period, VLF, LF, LF(nu), LF/HF were significantly increased and TSP, HF, HF(nu) were significantly decreased in restricted sleep individuals when compare to normal sleep individuals. In addition to this variation was more significant change respectively on 7th day, when compare with 4th day of restricted sleep period.

Fig. 2 Effect of restricted sleep on correlation between low frequency [LF(nu)and high frequency [HF(nu)] at 4th day of restricted sleep period.

Fig. 3 Effect of restricted sleep on correlation between low frequency [LF(nu)and high frequency [HF(nu)] at 7th day of restricted sleep period.

Among all normal and restricted sleep individuals, there was significant negative correlation between LF(nu) and HF(nu) at subsequent 4th day [r (48) = −0.84; P = 0.01] and 7th day[r (48) = −0.95; P = 0.01] of restricted sleep period.

5 Discussion

Partial sleep loss (sleep restriction) and/or accumulated sleep debt has been linked to health problems, including metabolic and cardiovascular disease.^23,24 Shift work may possibly have unfavorable effects on autonomic balance, increasing cardiac sympathetic and decreasing parasympathetic activity.^25,26 The main aim of this study was to test the hypothesis that partial sleep loss (sleep restriction) during night shift among night watchmen may be associated with an impaired cardiac autonomic modulation. Measurements of heart rate variability (HRV) are increasingly being used as a marker of cardiac autonomic activity during sleep¹⁴ and we are conscious that the use of time-domain measurements of heart rate variability as a tool to evaluate the autonomic input to the heart has its limitations, especially when applied to short-term recordings. The foremost limit of time-domain parameters is that they do not provide information about quantitative changes in the activity of each of its two components separately (sympathetic and parasympathetic). On the contrary, power spectral analysis of heart rate variability would provide more quantitative information regarding this.⁹ However, time and frequency domain measures are strongly interrelated, i.e. for every frequency domain measure there is a time domain measurement that strongly correlates with it (>0.85).²⁷ Even though it is assumed that sleep loss and the risk for CVD are interconnected,^28,29 however, only a small number of studies have reported higher sympathetic activity after partial sleep loss (sleep restriction).^17–19

The previous study of HRV based on ECG monitoring, observed that mental stress after sleep deprivation for 4 weeks, in healthy college students induces autonomic imbalance and altered HRV indices with an increase in norepinephrine.¹⁵ This study reveals that sleep loss associated with mechanisms of chronic mental and physical stress-induces cardiovascular events.¹⁵ Slow rhythms of HRV (LF) indicate increased sympathetic and/or lower vagal activity, wakefulness characteristics, whereas fast rhythms of HRV (HF) indicate lower sympathetic and/or increased parasympathetic and vagal activity, sleepy characteristics. Sleep-deprived subjects were exposed to real field driving conditions and ECG and EEG data were collected. A lower ratio of low frequency to high frequency components (LF/HF), and lower LF values were reported on the occurrence of driving errors. sleep-deprived drivers were lower in LF/HF and LF along with driving errors (related to sleepiness) than in those with no driving errors.³⁰ Cardiovascular autonomic modulation were also observed in normal subjects after 36-h sleep loss and shown increased LF and LF/HF as well as decreased HF as per baroreflex sensitivity, which is a measure of the ability of the HR to respond for changes in blood pressure.¹⁹ In addition to, one night of sleep loss has been also associated with decreased baroreflex sensitivity in normal individuals.²⁴

There have been a controlled laboratory-based investigations of the autonomic effect of acute sleep loss.¹⁴ In the present study, the alteration of HRV indices and a shift of sympathovagal balance toward sympathetic dominance is in consistent with those of earlier reports observed in young men after sleep restriction.¹⁹ The observation of the present study also reliable with work concerning sleep restriction over the course of 6 nights results in decreased glucose tolerance and increased sympathetic modulation as evaluated by HRV analysis.¹⁸ Similarly, long-term nighttime nurses were found to have higher LF and LF/HF when compared with regular shift nurses, supporting the current hypothesis that disturbed sleep affects cardiac SNS regulation.³¹ In another study, found that, individuals with frequent nightmares shown significantly higher LF and LF/HF, and lower HF when compare with healthy subjects.³²

Sleep loss may also altered the response of the sympathetic–adreno medullary (SAM) system and the hypothalamic–pituitary–adrenocortical (HPA) axis in addition to distressing the autonomic branch of the stress response system.⁶ The alteration in HPA axis response not only occurs after total sleep deprivation for a continuous period of two days, but it also gradually develops over time with chronic partial sleep restriction.³³ This sleep loss not only affects the basal activity of HPA axis but also its subsequent response to a psychological stressor. Rats subjected to prolonged total sleep deprivation or chronic partial sleep deprivation exhibited an altered HPA axis response to restraint stress.³³ and also induces a higher occurrence of ventricular premature beats.^34,35

Some of the previous studies have observed; there is a significant positive association between short sleep duration and higher BMI along with obesity.^36–38 However, our results are not consistent with higher BMI as well as with obesity within this period of restricted sleep, since we didn’t observe any significant change in BMI and body fat percentage in restricted sleep individuals, when compare to normal sleep individuals.

Hence, In view of these, data observed in this study, support the hypothesis that partial sleep loss (sleep restriction) may alters autonomic balance and shift toward sympathetic prevalence because increased low frequency spectral power is an indicator of increased sympathetic nervous system activity and this could be due to either an increase in sympathetic activity or a reduction in parasympathetic tone (or both) or may be an increases the sensitivity to stress-related ectopic activity, mainly consisting in ventricular premature beats. However, further research is needed to investigate the biological mechanisms that link short sleep duration and sympathetic dominance.

6 Conclusions

We conclude that partial sleep loss may cause autonomic imbalance represented by increased sympathetic and decreased parasympathetic activity; as revealed by altered HRV indices observed in this study. These conditions during sleep restriction may lead to increased risk for the development of cardiovascular disorders that are related to increased sympathetic nervous system activity. Therefore, this knowledge will be useful, to enabling risk factors to be modified and the potential to improve health outcomes among night watchmen with early accomplishment.

7 Limitations

The study was based only on men, therefore not allowing a study of the differences according to gender and we didn’t measure the cortisol level to assess the level of mental stress.

8 Conflict of interest

The authors declared no conflict of interest.

Acknowledgments

We gratefully acknowledge the financial support provided by the People’s University, Bhopal, India.

Notes

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 31 May 2017