Cited by 691Sleep and Work-Related FatigueCircadian rhythm and melatoninHeart Rate Variability and Autonomic Control

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Circadian misalignment increases cardiovascular disease risk factors in humans

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Morris, Christopher J., Purvis, Taylor E., Hu, Kun, Scheer, Frank A. J. L.·2016·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1516953113PMC PMC4790999

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Abstract

Significance: Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease, even after controlling for traditional risk factors. Shift workers frequently undergo circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles). This misalignment has been proposed to explain, in part, why shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. However, the impact of circadian misalignment per se on 24-h blood pressure and inflammatory markers is poorly understood. We show—under highly controlled laboratory conditions—that short-term circadian misalignment increases 24-h blood pressure and inflammatory markers in healthy adults. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

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Zhu, J., Liu, M.-Y., Qin, Q., He, J., Hu, M.-J., Zhu, Z.-Y., Liu, J., & Huang, F. (2023) · Journal of Occupational and Environmental Medicine · doi:10.1097/jom.0000000000002749 · Cited by 4
“Copyright © 2023 American College of Occupational and Environment rhythm and the work schedule, with long-term occurrence in shiftworkers, resulting in elevated mean blood pressure.(37) Previous research has shown that two main components of shiftwork may be related to the risk of high blood pressure, type of shiftwor…”
Background
Dispositional self-control: relationships with aerobic capacity and morning surge in blood pressure
May, R. W., Seibert, G. S., Sanchez‐Gonzalez, M. A., Fitzgerald, M., & Fincham, F. D. (2016) · Stress · doi:10.1080/10253890.2016.1260543 · Cited by 4
“…majority of acute adverse cardiac events occur in the morning hours; a greater understanding of factors associated with MBPS will have important clinical implications in the development of therapeutic targets for preventing cardiovascular complications (Morris et al., 2016; Sheppard et al., 2015).”
Background
Inflammatory Status and Cardio-metabolic Risk Stratification of Rotational Shift Work
Collins, B. E. G., Hartmann, T. E., Marino, F. E., & Skein, M. (2021) · Annals of Work Exposures and Health · doi:10.1093/annweh/wxab043 · Cited by 4
Sensor-Based Estimation of Dim Light Melatonin Onset Using Features of Two Time Scales
Wan, C., McHill, A. W., Klerman, E. B., & Sano, A. (2021) · ACM Transactions on Computing for Healthcare · doi:10.1145/3447516 · Cited by 6
“d shift work [13, 38], negatively affects human health, including increased risk for physical and psychiatric disorders [1], obesity [15] and increased 24-hour blood pressure and inflammatory markers [31]. Measuring human circadian phase (i.e., timing) accurately is essential for the clinical treatment of circadian mi…”
Background
The emerging significance of circadian rhythmicity in microvascular resistance
Kroetsch, J. T., Lidington, D., & Bolz, S. (2021) · Chronobiology International · doi:10.1080/07420528.2021.2009505 · Cited by 4
“In healthy human subjects, for example, acutely altering the normal wake/sleep cycle elicits a modest, but significant increase in blood pressure and circulating proinflammatory markers (Morris et al. 2016).”
Background
Comprehensive detrimental effects of a simulated frequently shifting schedule on diurnal rhythms and vigilance
Ma, X., Tian, Z., Li, Y., Gan, X., Li, S., Zhang, Y., Chen, S., Liu, S., Huang, Y. M., Yang, Y., et al. (2022) · Chronobiology International · doi:10.1080/07420528.2022.2101371 · Cited by 4
“…cardiovascular disease, excessive sleepiness, mood and social disorders, and cancer (Hara and Satake 2021; Haspel et al. 2020; Kawai 2022; Kecklund and Axelsson 2016; Kervezee et al. 2020; Morris et al. 2016; Salazar et al. 2021; Swiatkiewicz et al. 2021; Touitou et al. 2017; Wegrzyn et al. 2017).”
Background
Feeding Pattern, Circadian Rhythm, and Immune Function: What do we know about?
Estanislau, T. B., Kruger, K., Neto, J. C. R., Padilha, C. S., Gonçalves, D. C., Minuzzi, L. G., & Lira, F. S. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612828666220729091451 · Cited by 5
The Association between Earlier Bedtime and Cardiac Vagal Control in Community-Dwelling Older Adults: The Shi-Pai Sleep Study, Taiwan
Chang, S. W., Chen, H., & Chou, P. (2018) · Neuropsychiatry · doi:10.4172/neuropsychiatry.1000416 · Cited by 4
“However, most studies on the physiological impact of circadian misalignment have been limited to a younger population [16-18].”
Background
Longitudinal association between accelerometer-derived rest–activity rhythm and atherosclerotic cardiovascular disease
Huang, L., Li, Y., Xu, X., Chen, W., Zhang, Z., Sun, L., & Gao, X. (2024) · Sleep Medicine · doi:10.1016/j.sleep.2024.06.004 · Cited by 3
Vagal predominance correlates with mood state changes of winter-over expeditioners during prolonged Antarctic residence
Liu, S., Wang, J., Chen, S., Chai, J., Wen, J., Tian, X., Chen, N., & Xu, C. (2024) · PLoS ONE · doi:10.1371/journal.pone.0298751 · Cited by 3
Frequent Shifts During Chronic Jet Lag Uncouple Liver Rhythms From the Light Cycle in Male Mice
Zhang, Q., Litwin, C., Dietert, K., Tsialtas, I., Chen, W. H., Li, Z., & Koronowski, K. B. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304241311328 · Cited by 4
“…support the notion that misalignment contributes to phenotypes of energy balance (Scheer et al., 2009; Qian et al., 2019), fatty acid metabolism (Wefers et al., 2018; Harmsen et al., 2021), insulin sensitivity (Wefers et al., 2018), and relevant disease biomarkers (Morris et al., 2016).”
Dimorphic regulation of time-restricted feeding effects by hepatocyte Period 1
Sun, J., Higgins, C. B., Adams, J. A., Zhang, Y., Kelly, S. C., Kim, H., & DeBosch, B. J. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102270 · Cited by 3
Diurnal variation of wearable device-based heart rate variability in the Chronic Renal Insufficiency Cohort study
Skarke, C., Yang, W. C., Sha, D., Lahens, N. F., Isakova, T., Unruh, M. L., Deo, R., Carmona-Powell, E., Holmes, J. H., Ficarra, E., et al. (2025) · npj Digital Medicine · doi:10.1038/s41746-025-02010-5 · Cited by 3
“6 mmHghighersleep-timesystolicbloodpressure, 8 – 15% lowered wake-time cardiac vagal modulation, and 7% decreased 24-h urinary excretion rate of epinephrine (without affecting the overall 24-h urinary norepinephrine excretion rate) 4 .”
Late-Night Feeding, Sleep Disturbance, and Nocturnal Congestion Mediated by Hyperglycemia, Renal Sodium Retention, and Cortisol: A Narrative Review
Brown, R. B. (2025) · Clocks & Sleep · doi:10.3390/clockssleep8010001 · Cited by 3
“Circadian disruption—caused by shift work, late-night eating, or fragmented sleep—impairs glucose metabolism, alters renal sodium handling, and increases cardiometabolic risk [23].”
Exercise interventions for sleep and cognitive dysfunction in shift workers: a systematic review of randomized trials
Algharbi, F., Nuhmani, S., Alsubaiei, M., Shanb, A., & Alquaimi, M. M. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1762359 · Cited by 4
A newly developed circadian imbalance index (CII) and risk of cardiovascular-kidney-metabolic disease in the UK biobank
Zhang, J., Tran, D. T., Ghoul, T. E., Strohmaier, S., Żebrowska, M., Redline, S. S., Saxena, R., Rutter, M. K., & Schernhammer, E. S. (2026) · European Journal of Epidemiology · doi:10.1007/s10654-026-01373-7 · Cited by 4
Night-shift intensity, duration, cardiovascular susceptibility and incident cardiovascular disease: UK Biobank study
Lim, Y. (2026) · The American Journal of Medicine · doi:10.1016/j.amjmed.2026.06.016 · Cited by 3
Sleep disorders are closely associated with coronary heart disease in US adults (≥20 years): A cross-sectional study
Gan, T.-M., Yang, Y., Mo, G.-L., Wang, S.-R., Li, S.-H., & Li, J.-Y. (2024) · Medicine · doi:10.1097/md.0000000000039698 · Cited by 3
“The presence of such disorders can heighten the susceptibility to CVD. [22] Jankowiak et al [23] observed harmful changes in the atherosclerotic process associated with night work, with the duration of night shifts playing a significant role, potentially influenced by lifestyle and individual…”
Background
Seasonal timing and interindividual differences in shiftwork adaptation
Kim, R., Fang, Y., Lee, M., Kim, D. W., Tang, Z., Sen, S., & Forger, D. B. (2025) · npj Digital Medicine · doi:10.1038/s41746-025-01678-z · Cited by 3
“For example, it is known that heart rate is generally lowest during sleep 36 , but the circadian rhythms of heart rate can beoutofphasewiththesleep-wakecycle,andthisinternalmisalignmenthas beenassociatedwithanincreasedriskofcardiovasculardisease 37 andmental health risks 38,39 .”
The Role of Chrononutrition in Global Wellness
Fatima, G. (2025) · Chronobiology in Medicine · doi:10.33069/cim.2025.0016 · Cited by 4
Influence of circadian alignment and sleep timing variability on sex-specific inflammatory markers in healthy adults
Shafer, B. M., McAuliffe, K., Kogan, S. A., Davis, M. C., Shea, S. A., Olson, R., & McHill, A. W. (2025) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00735.2025 · Cited by 3
Circadian Rhythm and Stress
Steinach, M., & Gunga, H. (2019) · Springer eBooks · doi:10.1007/978-3-030-16996-1_9 · Cited by 4
Plasma metabolomics changes comparing daytime to overnight infusions of home parenteral nutrition in adult patients with short bowel syndrome: Secondary analysis of a clinical trial
Dashti, H. S., Sevilla-González, M. D. R., Mogensen, K. M., Winkler, M. F., & Compher, C. W. (2024) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2024.04.025 · Cited by 3
Multidimensional Sleep Health, Glycemic Control, and Self-reported Outcomes in Type 1 Diabetes: A Cross-sectional Study
Irsheed, G. A., Steffen, A. D., Martyn-Nemeth, P. A., Park, M., Quinn, L., Duffecy, J. L., Baron, K. G., Saleh, A. H., Takgbajouah, M., Bimbi, O., et al. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf032 · Cited by 5
Loss of diurnal oscillatory rhythms in gut microbiota correlates with progression of atherosclerosis
Zhang, H., Zhang, X., Yun, Z., Chen, Y., Cang, S., Shao, Y., Jia, E., & Chen, R. (2025) · Food & Function · doi:10.1039/d4fo05227g · Cited by 3
A snapshot in time: Does exercise training impact the muscle circadian clock in patients?
Schroder, E. A., & Delisle, B. P. (2016) · European Journal of Preventive Cardiology · doi:10.1177/2047487316651839 · Cited by 3
“Controlled studies in a laboratory environment with healthy human volunteers further cemented the link between circadian rhythms, metabolic and cardiovascular function, by demonstrating significant glucose handling and cardiovascular impacts in individuals exposed to a 28-hour day (dysynchrony) or circadian disruption…”
Background
On-shift naps are associated with systolic and diastolic blood pressure level among night working nursing professionals
Rotenberg, L., Silva‐Costa, A., & Griep, R. H. (2020) · Chronobiology International · doi:10.1080/07420528.2020.1819114 · Cited by 3
Night, Darkness, Sleep, and Cardiovascular Activity
Silvani, A. (2020) · Springer eBooks · doi:10.1007/978-3-030-28008-6_38 · Cited by 3
Circadian Misalignment and Cardiovascular Risk
Ashby, T., & Louis, M. (2019) · Cardiovascular Innovations and Applications · doi:10.15212/cvia.2017.0070 · Cited by 3
Behavioral Risk Factors
Thiriet, M. (2018) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-3-319-89315-0_6 · Cited by 3
Investigation on the Prediction of Cardiovascular Events Based on Multi-Scale Time Irreversibility Analysis
Wu, X., Yang, Q., Li, J., & Hou, F. (2021) · Symmetry · doi:10.3390/sym13122424 · Cited by 3
12h-clock control of central dogma information flow by XBP1sPreprint
Pan, Y., Ballance, H. I., Meng, H., Gonzalez, N., Dacso, C. C., Chen, X., Levy, O., Coarfa, C., O’Malley, B. W., & Zhu, B. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/559039 · Cited by 3
“…including but not limited to metabolic syndromes, cancer, sleep disorders, autoimmune diseases, brain disorders and cardiovascular diseases (Logan and McClung, 2019; Masri and Sassone-Corsi, 2018; Morris et al., 2016; Paganelli et al., 2018; Roenneberg and Merrow, 2016; Zhou et al., 2016).”
Background
Saturated Fat Impairs Circadian Transcriptomics through Histone Modification of EnhancersPreprint
Pillon, N. J., Puig, L. S., Altıntaş, A., Kamble, P. G., Casaní-Galdón, S., Gabriel, B. M., Barrès, R., Conesa, A., Chibalin, A., Näslund, E. B., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.23.432336 · Cited by 3
“16 DISCUSSION The circadian clock is a major regulator of whole-body metabolism through the control of gene expression, hormone levels, food intake and energy expenditure (7; 38; 39).”
Background
Cardiometabolic consequences of circadian disruption
Zhu, B., Hanlon, E. C., Knutson, K. L., & Reutrakul, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822963-7.00169-9 · Cited by 3
Calorie Restriction with or without Time-Restricted Eating in Weight Loss
Valenzuela, P. L., Castillo‐García, A., & Lucía, A. (2022) · New England Journal of Medicine · doi:10.1056/nejmc2207023 · Cited by 3
Rest Activity Rhythms and Their Association with Cardiorespiratory Fitness and Walking Energetics in Older Adults: Study of Muscle, Mobility, and Aging
Erickson, M. L., BLACKWELL, T. L., Garcia, R. E., Mau, T., Cawthon, P. M., Cummings, S. R., Farsijani, S., Sparks, L. M., Noone, J., Glynn, N. W., et al. (2025) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003730 · Cited by 2
“As noted by others, active disruption to circadian clock alignment is associated with pathophysiological outcomes including hypertension and glucose intolerance (37,38).”
Factors influencing heart rate variability in nurses following night shifts: a prospective observational clinical study
Zhan, T., Zhang, Z., Shi, Z., Xie, H., Zha, D., & Wei, X. (2025) · BMC Nursing · doi:10.1186/s12912-025-03975-0 · Cited by 2
“…systemic inflammation, with higher levels of biomarkers such as serum interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), and lipopolysaccharide-binding protein and higher leukocyte counts than those in daytime workers [8, 9].”
Lymphocytes and related inflammatory factors as predictors of metabolic syndrome risk in shift workers: A machine learning approach based on large-scale population data
Bao, Y., & Wang, R. (2025) · PLoS ONE · doi:10.1371/journal.pone.0339673 · Cited by 2
“Consistent with previous studies, alterations in shift patterns may modulate the activity of inflammatory cells through mechanisms such as circadian rhythm disruption, chronic stress, and increased metabolic load [45–47].”
Metabolic risk stratification of night shift workers in a large retail workplace through clustering and SHAP interpretation
Lee, I., Hong, S., Jang, E., Lee, J., & Lee, J. S. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2025.1704046 · Cited by 2
“These findings are closely related to the accumulation of metabolic risk over time in addition to the duration of shift exposure, suggesting that risk heterogeneity is evident even within the same shift worker group (34).”
The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer
Finger, A., Ector, C., & Weaver, V. M. (2026) · Cancers · doi:10.3390/cancers18060925 · Cited by 2
Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial
Tariq, A., Khalid, M. H., & Ammar, M. (2026) · Open Heart · doi:10.1136/openhrt-2025-003573 · Cited by 2
“3 As such, individuals differ not only”

Authors: Morris, C. J., Purvis, T. E., Hu, K., & Scheer, F. A. J. L.
Affiliations: Brigham and Women's Hospital (US)
ORCID: Purvis, Taylor E.
Hu, Kun
Scheer, Frank A. J. L.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2016-02-08
Volume: 113
Issue: 10
Pages: E1402-11
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1516953113
PMC: PMC4790999
OpenAlex: W2259214365
Cited by: 691
References: 81
Citations by year: 2026: 82 · 2025: 84 · 2024: 69 · 2023: 87 · 2022: 82 · 2021: 74 · 2020: 64 · 2019: 49 · 2018: 43 · 2017: 45 · 2016: 10
FWCI: 69.56
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Aeronautics and Space Administration (NCC958)
Brigham and Women's Hospital (UL1RR025758)
Harvard University (UL1RR025758)
National Space Biomedical Research Institute (P01 AG009975, NCC 9‐58)
National Institute on Aging (R01AG048108, P01AG009975)
National Heart, Lung, and Blood Institute (R00HL102241, R01HL118601, R01HL094806)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099512, DK099512)
National Center for Research Resources (UL1RR025758)
Topics: Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: circadian misalignment, shift work, cardiovascular risk, hypertension, blood pressure, sleep blood pressure, cardiac vagal modulation, heart rate variability, urinary epinephrine, urinary norepinephrine, inflammation, interleukin-6, C-reactive protein, resistin, TNF-α
MeSH terms: Adult, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Circadian Rhythm, Epinephrine, Female, Heart Rate, Humans, Hypertension, Male, Middle Aged, Risk Factors, Time Factors, Tumor Necrosis Factor-alpha, Work Schedule Tolerance, Interleukin-6, Polysomnography, Cross-Over Studies, Sleep Disorders, Circadian Rhythm, Resistin, Young Adult, Actigraphy

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Circadian misalignment increases cardiovascular disease risk factors in humans

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