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Adverse Impact of Sleep Restriction and Circadian Misalignment on Autonomic Function in Healthy Young Adults
Open accessAbstract
Insufficient sleep and circadian rhythm disturbances have been each associated with adverse cardiovascular outcomes in epidemiological studies, but experimental evidence for a causal link is scarce. The present study compares the impact of circadian misalignment (CM) to circadian alignment (CA) on human autonomic function using a nonrandomized parallel group design to achieve the same total sleep time in both conditions. After baseline assessments (3 days with 10-hour bedtimes), 26 healthy young adults were assigned to sleep restriction (SR; eight 5-hour bedtimes) with either fixed nocturnal bedtimes (CA; n=13) or bedtimes delayed by 8.5 hours on 4 of the 8 days (CM; n=13). Daytime ambulatory blood pressure and heart rate (HR; CA, n=11; CM, n=10) and 24-hour urinary norepinephrine levels (CA, n=13; CM, n=13) were assessed at baseline and the end of SR. Nocturnal HR and HR variability were analyzed during sleep at baseline and during the fourth and seventh nights of SR (CA, n=8; CM, n=12). SR resulted in a significant increase in daytime HR in both groups, without changes in blood pressure. SR increased 24-hour urinary norepinephrine in the CM group (30±4 versus 21±2 μg), but not in the circadian alignment group (group×condition, P =0.005). In contrast to the lack of detectable impact of CM on daytime autonomic function, SR with CM elicited greater increases in nocturnal HR, as well as greater reductions in vagal indices of HR variability, than SR without CM (group×condition, P <0.05). In conclusion, SR and CM both result in impaired autonomic function that could lead, under chronic conditions, to enhanced cardiovascular risk.
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“Sympathovagal balance is then disrupted [72], as indicated by changes in heart rate variability that are believed to reflect increased risk of cardiovascular disease (CVD) [73].”
From Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being (2017) · cites this paper as [72]
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Samson, D. R., & McKinnon, L. (2025) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2024.2319 · Cited by 8
Adherence to a healthy sleep pattern and new-onset acute kidney injury
Gan, X., He, P., Ye, Z., Zhou, C., Liu, M., Yang, S., Zhang, Y., Zhang, Y., & Qin, X. (2023) · Sleep Health · doi:10.1016/j.sleh.2023.09.010 · Cited by 9
Sleep disturbance and sympathetic neural reactivity in postmenopausal females
Tahsin, C. T., Anselmo, M. F., Lee, E. J., Stokes, W., Fonkoue, I. T., Noven, M. V., Carter, J. R., & Keller‐Ross, M. L. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00724.2023 · Cited by 8
Self-citationBlunted heart rate recovery to spontaneous nocturnal arousals in short-sleeping adults
Bigalke, J. A., Greenlund, I. M., Nicevski, J. R., Smoot, C. A., Oosterhoff, B. J., John‐Henderson, N. A., & Carter, J. R. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00329.2021 · Cited by 9
Self-citationDominiczak, A. F., & Kuo, D. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.10530 · Cited by 8
A federated semi-supervised automatic sleep staging method based on relationship knowledge sharing
Ma, B., Duan, L., Huang, Z., Qiao, Y., & Gong, B. (2023) · Expert Systems with Applications · doi:10.1016/j.eswa.2023.121427 · Cited by 7
Actigraphy-based sleep and muscle sympathetic nerve activity in humans
Bigalke, J. A., Greenlund, I. M., Bigalke, J. R., & Carter, J. R. (2024) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00113.2024 · Cited by 7
Self-citationTaking to “heart” the proposed legislation for permanent daylight saving time
Carter, J. R., Knutson, K. L., & Mokhlesi, B. (2022) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00218.2022 · Cited by 7
Self-citationSleep Deprivation and Its Consequences
Chernyshev, O. Y. (2023) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001323 · Cited by 7
Liang, X., Hou, Z., Chen, L., Wang, Y., Hua, K., & Sun, Y. (2023) · PubMed Central · doi:10.12182/20231160203 · Cited by 6
The validity and reliability of the Persian version of the Athlete Sleep Screening Questionnaire
Najafabadi, M. M., Angoorani, H., Charest, J., Samuels, C. H., Bagherzadeh, K., Nazari, A., & Mazaherinezhad, A. (2024) · Journal of Research in Medical Sciences · doi:10.4103/jrms.jrms_246_23 · Cited by 6
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“Although no prior study (to the best of our knowledge) has directly assessed the relationship between BISS and HRV, acute or chronic sleep insufficiency is known to adversely impact autonomic function [45, 46].”
BackgroundThe Correlation Between Sleep and Coronary Heart Disease: A Review
Shi, Q., Gao, Y., Shi, Z., & Li, M. (2025) · Reviews in Cardiovascular Medicine · doi:10.31083/rcm37252 · Cited by 5
“Sympathetic nervous system overactivation caused by poor sleep leads to an increased heart rate and reduced heart rate variability [109].”
Sleep and cardiometabolic risk. Narrative revision
Rodulfo, J. I. A., Aure, G., & Carrera, F. (2024) · Clínica e Investigación en Arteriosclerosis (English Edition) · doi:10.1016/j.artere.2024.01.001 · Cited by 5
Stražišar, B. G., & Stražišar, L. (2021) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2021.05.007 · Cited by 5
Sarıbal, D., Çalis, H., Ceylan, Z., Depciuch, J., Cebulski, J., & Güleken, Z. (2024) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2024.124702 · Cited by 5
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“Circadian misalignment refers to conditions of desynchronization between sleep-wake cycles and endogenous biological rhythms (Grimaldi et al. 2016).”
Arora, N., Brumpton, B. M., Åsvold, B. O., Loennechen, J. P., Malmo, V., Bhatta, L., Skarpsno, E. S., Richmond, R. C., & Strand, L. B. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf062 · Cited by 4
Alevroudis, I., Petridou, M., Sakkou, A., Kotoulas, S., Matzolas, S., Roumelis, P., Stougianni, M., Massa, E., & Mouloudi, E. K. (2025) · Reviews in Cardiovascular Medicine · doi:10.31083/rcm28244 · Cited by 4
“While most research on sleep deprivation or restriction has focused on plasma NOR, Grimaldi and colleagues [108] examined 24-hour urinary NOR following eight consecutive days of 5-hour sleep restriction.”
Sueño y riesgo cardiometabólico. Revisión narrativa
Rodulfo, J. I. A., Aure, G., & Viñoles, F. C. (2023) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2023.08.001 · Cited by 8
Weber, S., Mascherek, A., Augustin, J., Cheng, B., Thomalla, G., Hoven, H., Harth, V., Augustin, M., Gallinat, J., & Kühn, S. (2024) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1267900 · Cited by 4
Wang, L.-B., Zou, H.-X., Liu, X.-Y., Lu, X., Wang, J., Li, C., Zhang, S., Wu, S.-H., Yang, H.-Y., Zhou, Y., et al. (2025) · Hypertension Research · doi:10.1038/s41440-025-02380-z · Cited by 3
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Ponkilainen, V., Koukkula, T., Uimonen, M., Mattila, V. M., Kuitunen, I., & Reito, A. R. (2022) · PeerJ · doi:10.7717/peerj.13672 · Cited by 3
“In physiological level DST has been associated altered cortisol levels, increased levels of plasma pro- and anti-inflammatory markers and lower vagal tone (Grimaldi et al., 2016;Rishi et al., 2020;Wright Jr et al., 2015).”
Background
Metadata
- Authors
- Grimaldi, D., Carter, J. R., Van Cauter, E., & Leproult, R.
- Affiliations
- Michigan Technological University (US)
- From the Sleep, Metabolism and Health Center, Department of Medicine, The University of Chicago, IL (D.G., J.R.C., E.V.C., R.L.); and Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton (J.R.C.).
- Venue
- Hypertension
- Published
- 2016-07
- Volume
- 68
- Issue
- 1
- Pages
- 243-250
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC4902172
- OpenAlex
- W2414905660
- Cited by
- 153
- References
- 45
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 25 · 2023: 25 · 2022: 19 · 2021: 16 · 2020: 10 · 2019: 11 · 2018: 8 · 2017: 8 · 2016: 2
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - Michigan Tech (Michigan Technological University) (submittedVersion)
- Funders
- University of Chicago
- National Institutes of Health (UL1TR000430)
- National Institute on Aging (P01AG011412)
- National Heart, Lung, and Blood Institute (R01HL072694)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60DK020595, P30DK020595)
- NIH Clinical Center
- National Institute for Occupational Safety and Health (R01-OH009482)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- sleep restriction, circadian misalignment, circadian alignment, autonomic function, heart rate variability, urinary norepinephrine, blood pressure, nocturnal heart rate, cardiovascular risk, sleep deprivation, young adults
- MeSH terms
- Adult, Analysis of Variance, Autonomic Nervous System, Blood Pressure, Cardiovascular Diseases, Circadian Rhythm, Female, Heart Rate, Humans, Male, Sleep Deprivation, Time Factors, Polysomnography, Blood Pressure Monitoring, Ambulatory, Young Adult, Healthy Volunteers
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