Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.

Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggest a target for therapeutic intervention.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances.

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r = -.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r = -.31, P < .05) and positively associated with TNF level (r = .42, P < .01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

Carotid intimal medial thickness in rotating night shift is related to IL1ß/IL6 axis.

BACKGROUND AND AIMS: Sleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors. METHODS AND RESULTS: We measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y). R-NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1ß levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p < 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p < 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p < 0.001), with diastolic BP (p < 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489-4.776, p = 0.016). CONCLUSIONS: Our result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1ß/IL6 citokine axis connected to sleep disturbances.

Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility.

: Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called "clock genes" that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic-pituitary-gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.

Chocolate for breakfast prevents circadian desynchrony in experimental models of jet-lag and shift-work.

Night-workers, transcontinental travelers and individuals that regularly shift their sleep timing, suffer from circadian desynchrony and are at risk to develop metabolic disease, cancer, and mood disorders, among others. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental metabolic effects associated with circadian disruption. As an alternative, we hypothesized that a timed piece of chocolate scheduled to the onset of the activity phase may be sufficient stimulus to synchronize circadian rhythms under conditions of shift-work or jet-lag. In Wistar rats, a daily piece of chocolate coupled to the onset of the active phase (breakfast) accelerated re-entrainment in a jet-lag model by setting the activity of the suprachiasmatic nucleus (SCN) to the new cycle. Furthermore, in a rat model of shift-work, a piece of chocolate for breakfast prevented circadian desynchrony, by increasing the amplitude of the day-night c-Fos activation in the SCN. Contrasting, chocolate for dinner prevented re-entrainment in the jet-lag condition and favored circadian desynchrony in the shift-work models. Moreover, chocolate for breakfast resulted in low body weight gain while chocolate for dinner boosted up body weight. Present data evidence the relevance of the timing of a highly caloric and palatable meal for circadian synchrony and metabolic function.

Rapid suppression of bone formation marker in response to sleep restriction and circadian disruption in men.

We describe the time course of bone formation marker (P1NP) decline in men exposed to ~ 3 weeks of sleep restriction with concurrent circadian disruption. P1NP declined within 10 days and remained lower with ongoing exposure. These data suggest even brief exposure to sleep and circadian disruptions may disrupt bone metabolism. INTRODUCTION: A serum bone formation marker (procollagen type 1 N-terminal, P1NP) was lower after ~ 3 weeks of sleep restriction combined with circadian disruption. We now describe the time course of decline. METHODS: The ~ 3-week protocol included two segments: "baseline," ≥ 10-h sleep opportunity/day × 5 days; "forced desynchrony" (FD), recurring 28 h day (circadian disruption) with sleep restriction (~ 5.6-h sleep per 24 h). Fasted plasma P1NP was measured throughout the protocol in nine men (20-59 years old). We tested the hypothesis that PINP would steadily decline across the FD intervention because the magnitude of sleep loss and circadian misalignment accrued as the protocol progressed. A piecewise linear regression model was used to estimate the slope (ß) as ΔP1NP per 24 h with a change point mid-protocol to estimate the initial vs. prolonged effects of FD exposure. RESULTS: Plasma P1NP levels declined significantly within the first 10 days of FD ([Formula: see text] = - 1.33 µg/L per 24 h, p < 0.0001) and remained lower than baseline with prolonged exposure out to 3 weeks ([Formula: see text] = - 0.18 µg/L per 24 h, p = 0.67). As previously reported, levels of a bone resorption marker (C-telopeptide (CTX)) were unchanged. CONCLUSION: Sleep restriction with concurrent circadian disruption induced a relatively rapid decline in P1NP (despite no change in CTX) and levels remained lower with ongoing exposure. These data suggest (1) even brief sleep restriction and circadian disruption can adversely affect bone metabolism, and (2) there is no P1NP recovery with ongoing exposure that, taken together, could lead to lower bone density over time.

Delayed sleep-onset and biological age: late sleep-onset is associated with shorter telomere length.

STUDY OBJECTIVES: We evaluated the relationship between leukocyte telomere length (LTL) and sleep duration, insomnia symptoms, and circadian rhythm, to test whether sleep and chronobiological dysregulations are associated with cellular aging. METHODS: Data from the Netherlands Study of Depression and Anxiety (N = 2,936) were used at two waves 6 years apart, to measure LTL. Telomeres shorten during the life span and are important biomarkers for cellular aging. LTL was assessed by qualitative polymerase chain reaction and converted into base pair number. Sleep parameters were: sleep duration and insomnia symptoms from the Insomnia Rating Scale. Circadian rhythm variables were: indication of Delayed Sleep Phase Syndrome (DSPS), mid-sleep corrected for sleep debt on free days (MSFsc), sleep-onset time, and self-reported chronotype, from the Munich Chronotype Questionnaire. Generalized estimating equations analyzed the associations between LTL, sleep, and chronobiological factors, adjusted for baseline age, sex, North European ancestry, and additionally for current smoking, depression severity, obesity, and childhood trauma. RESULTS: Indicators of delayed circadian rhythm showed a strong and consistent effect on LTL, after adjustment for sociodemographic and health indicators. Late MSFsc (B = -49.9, p = .004), late sleep-onset time (B = -32.4, p = .001), indication of DSPS (B = -73.8, p = .036), and moderately late chronotype in adulthood (B = -71.6, p = .003) were associated with significantly shorter LTL across both waves; whereas sleep duration and insomnia symptoms were not. Extremely early chronotype showed significantly less LTL shortening than intermediate chronotype (B = 161.40, p = .037). No predictors showed accelerated LTL attrition over 6 years. CONCLUSIONS: Individuals with delayed circadian rhythm have significantly shorter LTL, but not faster LTL attrition rates.

Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome.

CONTEXT: To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS. OBJECTIVE: To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI. DESIGN: Cross-sectional study. PARTICIPANTS: Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33). OUTCOME MEASURES: Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis. RESULTS: All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing. CONCLUSION: Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.

Impact of Sleep Deprivation on Surgical Laparoscopic Performance in Novices: A Computer-based Crossover Study.

OBJECTIVE: The 24-hour work shifts are newly permitted to first-year surgical residents in the United States. Whether surgery novices' motor activity is affected by sleep deprivation is controversial. MATERIALS AND METHODS: This study assesses sleep deprivation effects in computer-simulated laparoscopy in 20 surgical novices following 24 hours of sleep deprivation and after resting using a virtual-reality trainer. Participants were randomly assigned to perform simulator tests either well rested or sleep deprived first. RESULTS: Of 3 different tasks performed, no significant differences in total time to complete the procedure and average speed of instruments were found. Instrument path length was longer following sleep deprivation (P=0.0435) in 1 of 3 tasks. Error rates (ie, noncauterized bleedings, perforations, etc.), as well as precision, and accuracy rates showed no difference. None of the assessed participants' characteristics affected simulator performance. CONCLUSIONS: Twenty-four hours of sleep deprivation does not affect laparoscopic performance of surgical novices as assessed by computer-simulation.

Gestational jet lag predisposes to later-life skeletal and cardiac disease.

Circadian rhythm disturbance (CRD) increases the risk of disease, e.g. metabolic syndrome, cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life.

Impact of Shift Work on the Circadian Timing System and Health in Women.

Women who do shift work are a sizable part of the workforce. Shift workers experience circadian misalignment due to shifted sleep periods, with potentially far-reaching health consequences, including elevated risk of sleep disturbances, metabolic disorders, and cancer. This review provides an overview of the circadian timing system and presents the sex differences that can be observed in the functioning of this system, which may account for the lower tolerance to shift work for women compared with men. Recent epidemiologic findings on female-specific health consequences of shift work are discussed.

Sleep Duration and Risk of Liver Cancer in Postmenopausal Women: The Women's Health Initiative Study.

BACKGROUND: Sleep duration has been associated with nonalcoholic fatty liver disease, but its association with liver cancer remains unknown. MATERIAL AND METHODS: In the prospective Women's Health Initiative Study, 139,368 postmenopausal women reported sleep habits at baseline (1993-1998). We ascertained 175 incident liver cancer cases during an average 13.8 years of follow-up through August 2014. We used multivariable Cox proportional hazard regression models to estimate a hazard ratio (HR) and its 95% confidence interval (95% CI) for risk of liver cancer in association with nocturnal sleep duration. RESULTS: Compared to women reporting 6-8 hours of sleep, the HR for liver cancer was 1.94 (95% CI 1.07-3.53) for women reporting ≥9 hours of sleep. Among the obese women, the HR associated with ≥9 hours of sleep was 3.18 (95% CI 1.84-8.60). The HR was 0.93 (95% CI 0.34-2.53) among nonobese women (p value for interaction = 0.18). Short sleep duration (≤5 hours) was not associated with liver cancer risk. CONCLUSION: Long sleep duration was associated with a moderate increase in liver cancer risk in obese postmenopausal women in the United States. Larger study is needed to confirm our observation on effect modification by adiposity status.

Características polisomnográficas nocturnas y otras variables relacionadas, en pacientes adultos mayores / Nocturnal polysomnbnographic characteristics and other related variables in elderly patients

Se cree que los ancianos necesitan dormir menos. Sin embargo, no es la necesidad de sueño sino la capacidad de dormir lo que disminuye con la edad, en paralelo a la mayor prevalencia de enfermedades cardiovasculares o metabólicas, o de depresión. Poco se ha descripto sobre los hallazgos polisomnográficos de esta población. En el presente estudio analizamos los hallazgos polisomnográficos en pacientes mayores de 65 años. Se realizó un estudio descriptivo a partir del análisis de una base de datos de 551 pacientes mayores de 65 años evaluados entre junio de 2013 y diciembre de 2014. Todos los sujetos se realizaron una polisomnografía (PSG) nocturna de 6 horas de duración. Las variables analizadas fueron: latencia de sueño (LS), eficacia de sueño (ES), latencia de fase REM (Lat R), % de R, índice de apneas hipopneas (IHA) y movimientos periódicos de piernas durante el sueño (PLMS). Se dividió la población en 3 grupos: G1: de 65 a 70 años; G2: 71 a 75; G3: mayor de 75 años. Se analizaron los datos de la serie general y las diferencias intergrupos. El IHA se incrementó con la edad y resultó más severo en los pacientes mayores de 75 años en relación con el grupo de menor edad. El incremento del IAH no se asoció a un incremento del índice de masa corporal ni a mayor somnolencia diurna. (AU)

It is believed that the elderly need less sleep. However, it is not the need for sleep but the ability to sleep that decreases with age, in parallel to the increasing prevalence of cardiovascular or metabolic disease, or depression. Little has been described about the polysomnographic findings of this population, hypothesizing that there are several alterations that prematurely corrected could improve the quality of life as the years go by. We analyzed the polysomnographic findings in patients over 65 years of age. A descriptive study was carried out based on the analyses of a database of 551 patients over 65 years of age evaluated between June 2013 to December 2014. All subjects underwent nocturnal PSG of 6 hours duration. The polysomnographic variables analyzed were: sleep latency (LS), sleep efficiency (ES), latency R phase (Lat R), % R, Apneas Hypoapneas Index (AHI) and Periodic Limb Movements of Sleep (PLMS). The population was divided into 3 groups: G1: from 65 to 70 years G2: 71 to 75, G3 greater than 75. AHI increased with age, being more severe in patients over 75 years of age in relation to the younger age group. The increase in AHI was not associated with an increase in Body Mass Index (BMI) or greater daytime sleepiness. (AU)

Evaluation of circadian phenotypes utilizing fibroblasts from patients with circadian rhythm sleep disorders.

We evaluated the circadian phenotypes of patients with delayed sleep-wake phase disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22.80±0.47 (mean±s.d.) h in control-derived fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived fibroblasts were 22.67±0.67 h and 23.18±0.70 h, respectively. The N24SWD group showed a significantly longer in vitro period than did the control or DSWPD group. Furthermore, in vitro period was associated with response to chronotherapy in the N24SWD group. Longer in vitro periods were observed in the non-responders (mean±s.d.: 23.59±0.89 h) compared with the responders (mean±s.d.: 22.97±0.47 h) in the N24SWD group. Our results indicate that prolonged circadian periods contribute to the onset and poor treatment outcome of N24SWD. In vitro rhythm assays could be useful for predicting circadian phenotypes and clinical prognosis in patients with CRSDs.

Shift Work and Shift Work Sleep Disorder: Clinical and Organizational Perspectives.

Throughout the industrialized world, nearly one in five employees works some form of nontraditional shift. Such shift work is associated with numerous negative health consequences, ranging from cognitive complaints to cancer, as well as diminished quality of life. Furthermore, a substantial percentage of shift workers develop shift work disorder, a circadian rhythm sleep disorder characterized by excessive sleepiness, insomnia, or both as a result of shift work. In addition to adverse health consequences and diminished quality of life at the individual level, shift work disorder incurs significant costs to employers through diminished workplace performance and increased accidents and errors. Nonetheless, shift work will remain a vital component of the modern economy. This article reviews seminal and recent literature regarding shift work, with an eye toward real-world application in clinical and organizational settings.

Are two halves better than one whole? A comparison of the amount and quality of sleep obtained by healthy adult males living on split and consolidated sleep-wake schedules.

The aim of this study was to compare the quantity/quality of sleep obtained by people living on split and consolidated sleep-wake schedules. The study had a between-groups design, with 13 participants in a consolidated condition (all males, mean age of 22.5yr) and 16 participants in a split condition (all males, mean age of 22.6yr). Both conditions employed forced desynchrony protocols with the activity:rest ratio set at 2:1, but the consolidated condition had one sleep-wake cycle every 28h (9.33+18.67), while the split condition had one sleep-wake cycle every 14h (4.67+9.33). Sleep was assessed using polysomnography. Participants in the split and consolidated conditions obtained 4.0h of sleep per 14h and 7.6h of sleep per 28h, respectively. Some differences between the groups indicated that sleep quality was lower in the split condition than the consolidated condition: the split sleeps had longer sleep onset latency (9.7 vs. 4.3min), more arousals (7.4 vs. 5.7 per hour in bed), and a greater percentage of stage 1 sleep (4.1% vs. 3.1%), than the consolidated sleeps. Other differences between the groups indicated that sleep quality was higher in the split condition than the consolidated condition: the split sleeps had a lower percentage of wake after sleep onset sleep (11.7% vs. 17.6%), and a greater percentage of slow wave sleep (30.2% vs. 23.8%), than the consolidated sleeps. These results indicate that the split schedule was not particularly harmful, and may have actually been beneficial, to sleep. Split work-rest schedules can be socially disruptive, but their use may be warranted in work settings where shiftworkers are separated from their normal family/social lives (e.g., fly-in fly-out mining) or where the need for family/social time is secondary to the task (e.g., emergency response to natural disasters).

Estimation methods for human circadian phase by use of peripheral tissues.

Almost all living organisms, including humans, exhibit diurnal rhythms of physiology and behavior, which are driven by the circadian clock. Many studies have found that chronic misalignment between circadian and environmental/social rhythms carries a significant risk of various disorders, including sleep disorders, metabolic syndrome, cardiovascular diseases and cancer. However, irregular sleep-wake cycles and circadian maladjustment often cause 'social jet lag', which is minor but chronic jet-lag in our daily lives. Establishment of objective and convenient circadian-phase estimation methods in the clinical setting would therefore greatly contribute not only to resolving this global health problem but also to developing chronomedicine, a clinical approach for optimizing the time of day of treatments. Traditional melatonin-based methods have limitations with respect to circadian-phase evaluation; however, estimation methods based on clock gene expression may be able to compensate for these limitations. As a representative application of circadian-phase estimation based on clock gene expression, our method of using hair follicle cells may aid in the rapid clinical detection of circadian-related sleep problems, especially circadian rhythm sleep disorders that are masked because of forced adaptation to social time schedules.

[Self-rated Caffeine Sensitivity: Implications for Personalized Sleep Medicine?]. / Individuelle Koffeinempfindlichkeit: Implikationen für eine personalisierte Schlafmedizin?

The prevalence of the insomnia syndrome and the effects of caffeine on sleep are in part genetically determined. Pharmacogenetic studies in humans demonstrate that functional polymorphisms of the genes encoding adenosine A2A receptors and dopamine transporters contribute to individual differences in impaired sleep quality by caffeine. The A2A receptor and dopamine transporter are preferentially expressed in the striatum. Together, these observations suggest that the striatum plays an important role in sleep-wake regulation. Individual caffeine sensitivity and A2A receptor genotype should be taken into account in the development of possible novel adenosine-based pharmacotherapies of sleep-wake disorders and neurodegenerative disorders such as Parkinson's disease. This may permit the prediction of individual drug effects and improve the reliability of clinical trials.

Work schedule and self-reported hypertension - the potential beneficial role of on-shift naps for night workers.

Data on the association between shift work and hypertension are controversial. Sleep restriction is hypothesized to be involved in this relationship. Since on-shift nap can partly compensate for sleep deprivation among night workers, this investigation is aimed at (i) comparing the prevalence of hypertension among workers considering both current and former night work, (ii) testing the association between on-shift naps and hypertension among night workers, and (iii) analyzing the influence of sleep complaints in the association between on-shift nap and hypertension. Nap was defined as a sleep episode with duration shorter than the average nighttime sleep. A cross-sectional study was performed at the 18 largest public hospitals in Rio de Janeiro, Brazil, in 2010-2011 (N = 2588 female registered nurses). Nurses were informally allowed to nap for up to three consecutive hours during working nights. Workers completed a multidimensional questionnaire including self-reported information on physician diagnosis of hypertension, napping, and sleep complaints (insomnia, diurnal sleepiness, and non-satisfactory sleep). Epidemiological and statistical treatment of data included binomial logistic regression and interaction tests. Higher chances of hypertension were observed for both current and former night workers compared with workers with no previous experience in night work, i.e. exclusive day workers (OR = 1.68; CI95% 1.22-2.33 and OR = 1.40; CI95% 1.01-1.96, respectively) after adjustment for age, race/ethnicity, physical activity, smoking, alcohol consumption, insomnia, weekly work hours, and BMI. Compared with exclusive day workers, both non-nappers and nappers were at a higher likelihood of reporting hypertension (OR = 1.93 CI95% 1.35-2.79 and OR = 1.41 CI95% 1.08-2.20, respectively). An interaction was observed between napping behavior and insomnia (p = 0.037). In the whole sample of night workers, the lower OR for nappers was confirmed when they were directly compared with non-nappers (OR = 0.76 CI95% 0.59-0.98). Analysis of night workers stratified by insomnia showed a significant reduction in OR for nappers (compared to non-nappers) only among insomniacs (OR = 0.58). Napping during night work may be a protective factor for hypertension, particularly among insomniacs. Factors related to melatonin secretion, blood pressure control, and blood pressure dipping patterns are likely to be involved in the relationship between on-shift napping and blood pressure.

Circadian misalignment increases cardiovascular disease risk factors in humans.

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.