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Circadian misalignment increases cardiovascular disease risk factors in humans
Open accessAbstract
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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“A recent laboratory study of shift workers revealed that circadian misalignment increased 24-hour BP and CV inflammatory markers including IL-6, C-reactive protein, and TNF-α (142).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [142]
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Meng, R., Cao, Y., Kong, Y., Wang, K., Yang, Z., Jia, Y., Dong, C., Duan, H., & Han, M. (2021) · Annals of Palliative Medicine · doi:10.21037/apm-20-2267 · Cited by 9
“Some studies have also found that the disturbance of circadian rhythm changes the 24-hour blood pressure of the subjects (11).”
BackgroundWatanabe, D., Yoshida, T., Watanabe, Y., Yamada, Y., Miyachi, M., Kimura, M., & the Kyoto-Kameoka Study Group (2022) · Journal of Epidemiology · doi:10.2188/jea.je20220215 · Cited by 9
“34 These results appear to support our fi nding of the strongest positive association with mortality risk in people with inadequate sleep quality and duration.”
ResultIntertwined relationship of dynamin-related protein 1, mitochondrial metabolism and circadian rhythm
Laxmi, I. P. L., Job, A. T., Manickam, V., & Tamizhselvi, R. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09430-8 · Cited by 9
Zheng, X., Jiang, M., Ren, X., Han, L., Yang, P., Jia, Y., Sun, L., Wang, R., Shi, M., Zhu, Z., et al. (2024) · Schizophrenia Bulletin · doi:10.1093/schbul/sbae070 · Cited by 9
Shafer, B. M., Kogan, S. A., Rice, S. P. M., Shea, S. A., Olson, R., & McHill, A. W. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae580 · Cited by 9
Yang, M., Lin, H. Y., Chen, Y. M., Hu, M., Chen, I., & Yang, C. (2025) · Biomedical Journal · doi:10.1016/j.bj.2025.100830 · Cited by 9
“Epidemiological studies show that engaging in excessive activities or experiencing sleep disruption during traditional “ rest" periods increases the risk of obesity, diabetes, cardiovascular disease, inflammation, and even cancer [4 – 7].”
Mylonas, V., Grigoriadis, S., Chalitsios, C., Stergiou, N., & Nikodelis, T. (2025) · Experimental Brain Research · doi:10.1007/s00221-025-07121-9 · Cited by 9
Night-shift work and its association with metabolic syndrome
Lin, S., Yeh, W.-C., Liu, Z.-X., Hsu, H.-F., & Chen, J. (2025) · Medicine · doi:10.1097/md.0000000000043598 · Cited by 9
“[9–11] Our study will explore the correlation between metabolic syndrome and night-shift work in a northern science and technology factory in Taiwan.”
Savvidis, C., Maggio, V., Rizzo, M., Zabulienė, L., & Ilias, Ι. (2025) · Medicina · doi:10.3390/medicina61091630 · Cited by 12
“These elevate CVD risk [24].”
InfluentialMultifaceted dynamics of circadian timing system influence aging and longevity
Jagota, A., Khan, Z. A., Sharma, S. A., & Priyanka (2025) · Biogerontology · doi:10.1007/s10522-025-10324-w · Cited by 9
“Moreover, chronic circadian and sleep disturbances are strongly associated with increased risk of coronary heart disease and adverse cardiac remodeling (Morris et al. 2016; Vetter et al. 2018; Jagota et al. 2019, 2021).”
Association Between Circadian Rest-Activity Rhythms and Incident Dementia in Older Adults
Wang, W., Wanigatunga, A. A., Etzkorn, L., Rabinowitz, J. A., Palta, P., Pike, J. R., Dougherty, R. J., Zipunnikov, V., Marino, F., Crainiceanu, C., et al. (2025) · Neurology · doi:10.1212/wnl.0000000000214513 · Cited by 10
Ramsey, A. M., Stowie, A. C., Hill, A., Ellis, I., Rhoads, M. K., Pollock, D. M., & Davidson, A. J. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00055.2023 · Cited by 9
Shafer, B. M., Christopher, D., Shea, S. A., Olson, R., & McHill, A. W. (2023) · Sleep Health · doi:10.1016/j.sleh.2023.08.010 · Cited by 9
Mikulska, A. A., Grzelak, T., Pelczyńska, M., Bogdański, P., & Czyżewska, K. (2021) · Biomolecules · doi:10.3390/biom11040517 · Cited by 8
“Other studies confirmed that the circadian misalignment in healthy adults and shift workers could cause a significant increase in blood pressure and inflammatory markers and lead to CVD [31,36], and maintaining normal blood pressure is associated with decreased risk of cardiovascular events and death [38].”
BackgroundInfluentialForced internal desynchrony induces cardiometabolic alterations in adult rats
de Oliveira, I. G. B., Ferreira-Junior, M. D., Lopes, P. R., Campos, D. B. T., Neto, M. L. F., Santos, E. H. R., Mathias, P. C. D. F., Francisco, F. A., Koike, B. D. V., Castro, C. H., et al. (2019) · Journal of Endocrinology · doi:10.1530/joe-19-0026 · Cited by 9
Park, S., & Colwell, C. S. (2019) · PubMed Central · Cited by 9
Bose, K., Agrawal, R., Sairam, T., Mil, J., Butler, M. P., & Dhandapany, P. S. (2024) · iScience · doi:10.1016/j.isci.2024.109075 · Cited by 9
Damara, M., Misra, N., & Chambon, P. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2403770121 · Cited by 8
“G ), similar to those previously reported for “RF30 misaligned” mice (3–6) and night - shifted workers (7–10, 32– 34).”
ResultShukla, A., Sharma, C., Malik, M. Z., Singh, A. K., Aditya, A. K., Mago, P., Shalimar, S., & Ray, A. K. (2025) · Journal of Environmental Management · doi:10.1016/j.jenvman.2025.124693 · Cited by 11
Sukor, A. N. A., Juliana, N., Hamid, N. A., Teng, N. I. M. F., Ithnin, M., Azmani, S., & Kasim, S. S. (2025) · Biomedicines · doi:10.3390/biomedicines13102539 · Cited by 13
Tran, D. T., Strohmaier, S., Żebrowska, M., Huang, T., Papantoniou, K., Redline, S. S., Saxena, R., Rutter, M. K., & Schernhammer, E. S. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf774 · Cited by 8
Stride‐to‐Stride Fluctuations of Human Gait Are Affected By Chronobiology: An Exploratory Study
Vaz, J. R., Silva, L., & Stergiou, N. (2023) · Advanced Biology · doi:10.1002/adbi.202200235 · Cited by 8
Ho, L.-J., Sheu, W. H., Lo, S.-H., Yeh, Y., Hwu, C., Huang, C., Hsieh, C., & Kuo, F.-C. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01018-9 · Cited by 11
“Additionally, dysregulated lifestyle behaviors associated circadian disruption also increases inflammatory markers including CRP [27, 28], TNF-alpha [27, 28], IL-6 [27], IL-10 [28], and resistin [27].”
BackgroundKuntić, M., Hahad, O., Al-Kindi, S. G., Oelze, M. W., Lelieveld, J., Daiber, A., & Münzel, T. F. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2024.0659 · Cited by 10
“Disturbance of circadian rhythms is a potent trigger of in fl ammation, oxidative stress, arterial hypertension and other cardiovascular risk factors (Morris et al., 2016; Crnko et al., 2019), and chronotherapy by melatonin was shown to reduce blood pressure in patients with essential hypertension…”
Global burden of stroke attributable to dietary risk factors in the GBD 2021 study
Xie, W., Li, A., Zhang, Y., Tan, S., & Luo, J. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1494574 · Cited by 8
Rhoads, M. K., Speed, J. S., Roth, K. J., Zhang, D., Jin, C., Gamble, K. L., & Pollock, D. M. (2022) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00287.2021 · Cited by 8
When the clock ticks wrong with COVID‐19
Papagerakis, S. M., Said, R. S., Ketabat, F., Mahmood, R., Pundir, M., Lobanova, L., Guenther, G., Pannone, G., Lavender, K. J., McAlpin, B. R., et al. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.949 · Cited by 8
Sultan, A. (2018) · Biological Rhythm Research · doi:10.1080/09291016.2018.1498197 · Cited by 8
“…as cancer (Filipski and Lévi 2009; Papagiannakopoulos et al. 2016; Sultan et al. 2014, Sultan et al. 2017b, 2017c, 2017d), cardiovascular disease (Morris et al. 2016), metabolic syndrome (Maguire et al. 2017), sleep and affective disorders (Bedrosian and Nelson 2017; Rijo-Ferreira et al. 2018),…”
BackgroundThe influence of shift work on metabolic health
Tsvetkova, E. S., Romantsova, T. I., Евгеньевна, Р. Г., Сергеевич, Б. Н., & Goldshmid, A. E. G. (2019) · Obesity and metabolism · doi:10.14341/omet10015 · Cited by 9
“Ночью эвакуация содержимого из желудка замедляется [47, 55]. В серии экспериментов in vitro и in vivo выявлен четкий циркадианный ритм высвобождении ГПП-1 из L-клеток кишечника у крыс и человека [60–62]. У грызунов наблюдается явная циркадианная ритмичность секреции ГПП-1, совпадающая по фазе с секрецией инсулина, с п…”
Circadian Deregulation as Possible New Player in Pollution-Induced Tissue Damage
Benedusi, M., Frigato, E., Bertolucci, C., & Valacchi, G. (2021) · Atmosphere · doi:10.3390/atmos12010116 · Cited by 8
Cruz, M. G. M. E., & Acuña-Castroviejo, D. (2018) · Internal and Emergency Medicine · doi:10.1007/s11739-018-1934-7 · Cited by 8
Kado, D. M. (2024) · SLEEP · doi:10.1093/sleep/zsae005 · Cited by 8
Eveningness is associated with coronary artery calcification in a middle-aged Swedish population
Frisk, M. K., Fagman, E., Arvidsson, D., Ekblom, Ö. B., Börjesson, M., Bergström, G. M. L., & Zou, D. (2023) · Sleep Medicine · doi:10.1016/j.sleep.2023.11.004 · Cited by 7
“Third, the circadian system may have direct impacts on vascular senescence through influence on telomerase activity as well as regulation of antioxidant enzymes and inflammatory factors [43, 52].”
BackgroundNight shift work and myocardial infarction in the UK Biobank
Yang, M. J., Jia, Z. W., Wang, E., Li, J., Tang, A. M., Song, Z., & Zhang, Z. (2024) · Occupational Medicine · doi:10.1093/occmed/kqae045 · Cited by 7
Hypertension disrupts the vascular clock in both sexes
Visniauskas, B., Ogola, B. O., Kilanowski‐Doroh, I., Harris, N. R., Diaz, Z. T., Horton, A. C., Blessinger, S. A., McNally, A. B., Zimmerman, M. A., Arnold, A. C., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00131.2024 · Cited by 8
Metadata
- Authors
- Morris, C. J., Purvis, T. E., Hu, K., & Scheer, F. A. J. L.
- Affiliations
- Brigham and Women's Hospital (US)
- 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
- 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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