Circadian misalignment and cardiovascular health, from shift work to social jetlag : a chronotype based approach
Year: 2021
Type: dissertation
Abstract: Circadian rhythms (from the Latin circa diem meaning “about a day”) are biological cycles endogenously generated. These rhythms are self-sustained, have a period of approximately 24h and are generated by an internal biological master clock, which entrains (synchronizes) to environmental cues. The 24h light–dark cycle, resulting from the Earth's rotation on its own axis, is the major synchronizer shaping several aspects of physiology and behavior of species from all phyla. Individual differences in how the human biological clock entrains to the 24h day – earlier or later, (e.g., in reference to dawn) – are expressions of different chronobiological traits (i.e., chronotypes). Chronotype ranges from extreme early/morning-types to extreme late/evening-types (the colloquial larks and owls), with the majority of people standing in between, presenting an approximately Gaussian distribution in the population. The Munich ChronoType Questionnaire (MCTQ) estimates chronotype through individuals’ sleep phase, assessing current sleep–wake behavior separately for work and work-free days. An MCTQ-derived chronotype is a continuous variable expressed in local time, the Midpoint of Sleep on Free days, corrected for sleep debt accumulated through weekdays (MSFsc). In addition to chronotype, MCTQ estimates the amount of strain on the biological circadian system exerted by social commitments, measured as the Social JetLag (SJL). SJL is a continuous variable expressed in hours and it is considered a proxy (and a quantitative marker) for the circadian misalignment. Circadian misalignment can emerge as a consequence of social obligations when there is a discrepancy between the internal sleep window (mostly driven by chronotype) and the social sleep opportunity (mostly driven by working schedules). Circadian misalignment can be transient, such as in transmeridian travels (i.e., jetlag) but it can be chronic, such as in shift work. Shift work affects more than 20% of the European workforce and has long been associated with an increased risk for chronic diseases and injuries. Major pathophysiological mechanisms that explain this link include circadian misalignment, sleep disturbances, unhealthy behaviors and psychosocial stress. The association between shift work and cardiovascular diseases has been researched for more than two decades and one systematic review showed that shift work was associated with a 23% increased risk of ischemic heart disease and 5% for stroke. Cardiovascular diseases are a major cause of morbidity and mortality in modern societies and guidelines on cardiovascular prevention stress the importance of non-traditional risk factors, such as occupational factors. Therefore, innovative ways to address cardiovascular health, especially among working adults are needed. To date, knowledge about the health impact of circadian misalignment and the role of the chronobiological inter-individual differences in real-life working settings is scarce. This thesis aims to improve knowledge in this field by revising the evidence concerning the cardiovascular consequences of different types of shift work and by exploring the role of social jetlag in the cardiovascular risk of shift workers. To achieve this aim, three studies were performed: Study 1 aimed to review and synthesize the existing scientific literature concerning the impact of different types of shift work both on systolic and diastolic blood pressure values and in the hypertension risk of shift workers, in comparison with day workers. A systematic review and meta-analysis were performed according to the PRISMA guidelines. Forty-five independent studies assessing ~117 thousand workers were included. The most frequent shift work type was “rotational shifts including night work” (n=28), followed by “permanent night work” (n=14) and “rotational shifts without night work” (n=4). Meta analysis pooled results reveal that: 1) permanent night workers had a significant increase in both systolic and diastolic blood pressure values; 2) rotational shift workers, both with and without night work, had a significant increase, only in systolic blood pressure; 3) no shift work type significantly influenced the risk of hypertension. The magnitude of the effect was rather small, ranging from 0.65 to 2.52 mmHg, and the larger upper bound of the pooled confidence intervals was 4.29 mmHg. This might seem not clinically significant, however, it should be considered in susceptible populations continuously exposed over a long period of time to shift work, as a possible contributing factor for the development of hypertension and/or for the need of more intensive drug treatment. Moreover, these results highlight the heterogenous aspect of shift work as a potential risk factor and reinforces the need for a more tailored assessment of the potential risks associated with shift work exposure. Study 2 aimed to validate the European Portuguese variant of the Munich Chronotype Questionnaire (MCTQ) to the adult population living in Portugal, using subjective and objective measures. We made the cross-cultural adaptation of the original MCTQ to develop the Portuguese variant (MCTQPT), and we explore its psychometric properties. A cross-sectional observational study including 80 volunteers (age and gender balanced according to the Portuguese distribution) filled out the MCTQPT and used actimetry for 4 weeks to objectively assess the sleep–wake cycle. Additionally, we compared MCTQPT results to the most widely used chronotyping questionnaire (i.e., MEQ. Results show that MCTQ key variables correlated highly with their counterparts calculated from actimetry (MSW: rho = 0.697; MSF: rho = 0.747; MSFsc: rho = 0.646; SJL: rho = 0.452; all p < 0.001). The MCTQ assessment of the chronotype showed very good test–retest reliability (rho = 0.905; p< 0.001). Therefore, MCTQPT proved to be a simple and valid instrument to assess chronotype and social jetlag among the Portuguese population. Study 3 aimed to investigate the association between social jetlag, as a measure of circadian misalignment, and cardiovascular risk, estimated from modifiable risk factors in a population of blue-collar workers following permanent atypical schedules. A cross-sectional observational study including 301 workers, who either worked morning, evening, or night shifts, filled out the MCTQPT and had major risk factors measured (blood pressure, total cholesterol, and smoking status) to estimate the cardiovascular relative risk SCORE. Our results showed that higher levels of social jetlag were associated with worse cardiovascular parameters. A higher degree of social jetlag was independently associated with greater odds of having a high cardiovascular relative risk, even after adjusting for sociodemographic, lifestyle, sleep, and work variables. This risk increased 31% for each additional hour of social jetlag that the worker is exposed to (odds ratio 1.31, 95% confidence interval 1.02– 1.68). Additionally, higher levels of working productivity were found among workers with less amount of social jetlag. To our knowledge, this was the first study indicating that social jetlag potentially increases cardiovascular risk and suggests that sleep and individual circadian traits (i.e., chronotype) are conceivably useful in preventing the health consequences of shift work. Our results support interventional studies on optimizing working schedules, that is, to test if the allocation of working schedules in accordance with the worker’s chronotype (e.g., early chronotypes are assigned to early shifts) have favorable results in both health and corporate outcomes. We conclude that the health consequences of shift work depend on both the characteristics of the work schedule and the individual chronobiological characteristics of the person who performs it. Effective ways to improve health and performance of shift workers are pressing and the solution might rely on the diversity of human chronotypes.
Author: Madeira, Sara Alexandra Gamboa
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7008610202