Night shift work and cardiovascular diseases

Summary

Deleterious effects of night work on human biological functions are a very current issue. The aim was to review the available literature to assess the impact of shift work (namely at night) on workers’ health, particularly with respect to the risk of developing cardiovascular diseases. Shift work has a negative effect on the development of cardiovascular disease risk factors. There are several complex pathophysiological hypotheses explaining how shift work contributes to cardiovascular diseases. Most likely, the cause is multifactorial effects of circadian dysregulation, sleep deprivation, negative behavioral changes in lifestyle and occupational stress. Assessing the impact of shift/night work on workers’ health and mechanisms responsible for that may be useful for developing preventive strategies.

Keywords:

night work – night shift – shift work – Sleep deprivation – risk factor

METHODS

To obtain relevant studies written in English language, the following internet databases were searched: relevant sections of the Cochrane Library, EBSCO Discovery Service, PubMed and ScienceDirect. The keywords night shift, shift work and working hours were individually combined with the terms cardiovascular disease, cardiovascular risk factors and circadian stress. Entries published between the end of 2000 and 2018 were processed. Also included in the analysis were some articles cited in reference lists in the retrieved studies.

INTRODUCTION

According to the latest WHO update, cardiovascular diseases (CVDs) are the main cause of death globally. An estimated 17.7 million people died from CVDs in 2015, representing 31% of all global deaths. Of these deaths, an estimated 7.4 million were due to coronary heart disease (CHD) and 6.7 million were due to stroke [1]. Based on 34 studies and over 2 million employees, the systematic review of Vyas et al. [2] concluded a few years ago that shift work was associated with incident myocardial infarction, with a risk ratio of 1.23 [95% confidence interval (CI) 1.15–1.31]. In this issue, a more recent systematic review and meta-analysis on shift work and the risk of CVD is published. Based on 21 studies, including 10 new ones since the publication of Vyas et al., Torquati and colleagues [2] found that shift work was associated with CHD morbidity with a pooled risk ratio of 1.26 (95% CI 1.10–1.43) and about 20% increased risk of death from CHD or CVD. The study also reports that risk of CVD events increased by 7.1% for every five years of exposure.

The relationship between modifiable risk factors for CVDs and night shift work was investigated in a cross-sectional study among blue-collar workers employed in industrial plants [3]. The study found that among female current night shift workers, the prevalence of current smoking and overweight was higher when compared to both, never or former night shift workers. Frequency of recreationally active (≥ 2 h per week) women was lower in both current and former night workers when compared to never night shift workers. Among men, recreational inactivity was significantly associated with current night shift work when compared to never night shift workers (odds ratio 2.43, 95% CI 1.13–5.22).

Higher levels of job-related strain associated with exhaustion in nurses working night shifts as compared to day nurses was shown in an Italian cross-sectional study by Buja et al. The study also correlated night shift work with more visits to a doctor, a higher incidence of gastric pain and a greater use of painkillers [4].

Although some pathophysiological mechanisms related to shift work and a subsequent increase in CVD risk factors have already been described, many associations are still to be elucidated [5, 6].

Metabolic syndrome, overweight/obesity and type 2 diabetes mellitus

In the last decades, numerous studies, both cross-sectional and prospective, have consistently informed about an inverse relationship between sleep duration and body weight in both children and adults [7–9]. In shift workers, the incidence and degree of obesity were related to shift work duration. A significant increase in waist-to-hip ratio was found in workers after two to five years and increased body mass index (BMI) after more than five years of shift work [10]. A causal relationship between sleep debt and weight gain was confirmed by studies [11, 12].

A systematic review performed by Van Drongelen et al. provided convincing evidence about an association between shift work and increased body weight. Moreover, behavior changes potentially linked to shift work such as reduced physical activity may independently contribute to weight gain and the development of associated conditions such as metabolic syndrome (MetS) and type 2 diabetes mellitus. However, generalization of such findings is limited by the heterogeneity of studies included in the review. The studies varied in methods used and follow-up periods, the control of confounding factors and shift work definitions [13].

In a study by Di Lorenzo et al., obesity was more frequently observed in shift workers (20.0%) than in day workers (9.7%). Shift work was found to be associated with BMI, irrespective of age or time of exposure to shift work [14].

Additionally, high dietary fat intake during the night in shift workers (40% of all calories) results in a considerable postprandial increase in triglycerides and unsaturated fatty acids [15, 16]. Sleep deprivation seems to alter the regulation of leptin and ghrelin production, potentially leading to increased food intake, a risk factor for obesity. Estimations of sympathovagal balance derived from recordings of heart-rate variability were significantly higher during restricted sleep [11]. Increased sympathetic activity may be associated with metabolic (e.g. insulin resistance) and cardiovascular changes. This involves a higher incidence of obesity in shift workers [10, 17].

The development of insulin resistance, a key pathogenetic step in MetS, is directly contributed to by dysregulated secretion of melatonin known to play a role in regulating the expression of the glucose transporter 4 and its phosphorylation [18]. In their retrospective cohort study, Lin et al. showed an accelerated development of MetS in 387 individuals with persistent rotating shift work exposure (odds ratio 3.5, 95% CI 1.3–9.0) as compared with day workers [19].

A 2014 meta-analysis by Wang et al. summarizing studies on night shift work and the risk of MetS confirmed the relationship. Moreover, there was a direct association between the length of exposure to night shift work and an increased risk of MetS [20].

Similar findings were reported by Chang et al. who studied the relationship between sleep duration and quality and MetS in male Taiwanese police officers. Those with higher scores of sleep disturbances had a higher prevalence of MetS and abdominal obesity. After adjusting for age, low-density lipoprotein cholesterol, smoking status, alcohol drinking habit, physical exercise, snoring and type of shift work, those who slept less than five hours were 88% more likely to suffer from abdominal obesity than those who slept 7-7.9 hours (95% CI 1.01–3.5) [21].

All these risk factors together may add to the risk of CVDs in night shift workers [10, 17].

Hypertension

A risk of hypertension increased by 10% was reported in some studies while others found a 23% increase in hypertension and a loss/impairment of the normal variability of blood pressure (a lack of blood pressure drop when sleeping). Thus, shift work is likely to have a negative impact on blood pressure and its natural variability [6].

A cross-sectional study among 4307 female nurses and nursing assistants in seven French hospitals found that night shift workers had their systolic blood pressure raised by 2.5 mmHg when compared to day workers [22].

A Japanese study compared the results of annual health check-ups in male day workers and alternating shift workers between 1991 and 2005. Shift workers were found to have raised arterial pressure even after adjustment for confounding variables. These findings suggest that shift work may be an independent risk factor for increased blood pressure levels irrespective of the known risk factors such as age and BMI [23].

CONCLUSIONS AND FUTURE PROSPECTS

Shift work has a negative impact on CVD risk factors and is thus associated with an increased risk for their development. There are several complex pathophysiological hypotheses explaining how shift work contributes to CVDs. Most likely, the cause is multifactorial effects of circadian dysregulation, sleep deprivation, negative behavioral changes in lifestyle and occupational stress. Numerous studies have shown that shift work (in particular at night) is linked to a higher prevalence of risk factors (MetS with all its components, cigarette smoking and physical inactivity) but the available results are inconsistent (especially those related to certain risk factors). The main mechanism involved in the progression of atherosclerosis is an increased level of blood lipids. Assessing the impact of shift/night work on workers’ health and mechanisms responsible for that may be useful for developing preventive strategies.

At present, relatively many studies are available on the effect of shift work, including night work, on workers’ health. These studies clearly suggest that the impact is negative. However, these studies vary in design, with different samples, settings, workloads, exposure to shift work and proportion of night work being used; the recorded events/incidents mostly include fatalities only but not stable angina pectoris. Thus, these studies yield relatively heterogeneous data and not really conclusive results. This is probably why a clear mechanism of the effect of shift/night work on the human organism has not yet been elucidated. Future research should use established definitions of conditions to ensure that studies are comparable.

To conclude, a practical solution is preventing negative effects of lifestyle, monitoring and subsequent education. Thus, the recommendations for practice could be as follows. During regular medical check-ups, physicians should ask patients about their working time arrangements and tolerance to shift/night work.

Since shift work may contribute to arterial hypertension, blood pressure should be regularly monitored. It is also necessary to take into consideration how much time has elapsed since the end of the last shift and to perform a check-up after a day’s rest.

Shift work accelerates the development of MetS (typically, triglycerides are increased). For early detection of abnormalities in carbohydrate and fat metabolism or to detect weight gain, regular biochemical screening and anthropometric measurements should be regularly performed. Shift workers should be offered counselling about cardiovascular risk prevention (e.g. dietary measures, physical activity, smoking and alcohol consumption).

Administration of exogenous melatonin before the beginning of the so-called biological night or during its initial part may help induce sleep or accelerate its onset. The application of melatonin also promotes a return to a normal sleep pattern after night shifts; this is often used in cases of shift work intolerance. So far, neither serious adverse effects nor the development of tolerance to melatonin have been observed [24].

Sleep deprivation has been repeatedly associated with inflammatory responses not only in animal studies. This fact can be significant in the context of the well known inflammatory etiopathogenesis of many CVDs. Decreasing sleep deprivation-induced inflammatory responses could potentially reduce negative effects of night work on the cardiovascular system. In an animal study, probiotics were shown to prevent a sleep deprivation-induced elevation of inflammatory cytokines in the brain and serum. Further research will show whether measures aimed to reduce inflammatory responses are able to limit the negative effects of night work [25].

In case of inadequate or insufficient daylight, light therapy may be an option. Available are, for example, special glasses emitting white light specifically enriched with blue light (470 nm wavelength) to which eye photoreceptors are most sensitive. These glasses are indicated to treat sleep disorders, circadian dysregulation, jet lag or seasonal affective disorder.

Do redakce došlo dne 21. 6. 2018.

Do tisku přijato dne 9. 7. 2018.

Adresa pro korespondenci:

MUDr. Ladislav Štěpánek

Klinika pracovního lékařství Fakultní nemocnice Olomouc

I. P. Pavlova 185/6

779 00 Olomouc

e-mail: ladislav.stepanek@fnol.cz