Impact of the human circadian system, exercise, and their interaction on cardiovascular function
Open accessAbstract
The risk of adverse cardiovascular events peaks in the morning (≈9:00 AM) with a secondary peak in the evening (≈8:00 PM) and a trough at night. This pattern is generally believed to be caused by the day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough ≈85% of mean, peaking at a circadian phase corresponding to ≈9:00 AM) and in circulating catecholamines (epinephrine, ≈70%; norepinephrine, ≈35%, peaking during the biological day). At ≈8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks: at ≈noon and ≈11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at ≈9:00 AM and peaks in catecholamine reactivity at ≈9:00 AM and ≈9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.
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The reactivities to exercise of both epinephrine and norepinephrine exhibited 12-hour rhythms with large peaks at circadian phases corresponding to 0700-1030 and 2000-2200 hours.
“Rather than a simple 24-hour rhythm, the reactivities to exercise of both epinephrine and norepinephrine exhibited 12-hour rhythms with large peaks at circadian phases corresponding to 0700-1030 and 2000-2200 hours.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
Using three stringently controlled constant routine and forced desynchrony protocols that overcame limitations of earlier studies, robust endogenous circadian rhythms in blood pressure were discovered.
“In contrast, using three stringently controlled constant routine and forced desynchrony protocols that overcame these limitations, robust endogenous circadian rhythms in BP were discovered (83,90).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
Exercise-induced increases in epinephrine were twice as large in the morning (0830 hours) than in the middle of the night (0430 hours).
“Notably, exercise-induced increases in epinephrine were twice as large in the morning (0830 hours) than in the middle of the night (0430 hours) (90).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
Efferent cardiac vagal tone (estimated from heart rate variability) has a circadian peak at approximately 8 am, coincident with the circadian basal blood pressure trough, suggesting that circadian rhythms of blood pressure and parasympathetic nervous system activity may be mechanistically related in resting healthy individuals.
“On the other hand, the efferent cardiac vagal tone (estimated from HR variability) had a circadian peak at approximately 8 am, coincident with the circadian basal BP trough (90), suggesting that circadian rhythms of BP and parasympathetic nervous system activity may be mechanistically related in resting healthy individuals.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
The large time lag between the circadian peaks in sympathetic nervous system activity and blood pressure suggests that blood pressure's circadian rhythm is not driven by the sympathetic nervous system.
“The large time lag between the circadian peaks in sympathetic nervous system activity and BP (90) suggest that BP's circadian rhythm is not driven by the sympathetic nervous system.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
There were significant circadian rhythms in the reactivity of parasympathetic markers, with the greatest cardiac vagal withdrawal during exercise across the morning period.
“There were also significant circadian rhythms in the reactivity of parasympathetic markers, with the greatest cardiac vagal withdrawal during exercise across the morning period.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
The amplitudes of basal resting blood pressure rhythms are small in healthy people (group average 3- to 6-mmHg peak-to-trough amplitudes) but may have clinical relevance, as they doubled upon exercise.
“The amplitudes of basal resting rhythms are small in healthy people (group average 3-to 6-mmHg peak-to-trough amplitudes) but may have clinical relevance, as they doubled upon exercise (90).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
Sympathetic tone (circulating epinephrine and norepinephrine) has large endogenous circadian rhythms (peak-to-trough amplitudes of 70% and 34% of the mean, respectively) that peak at a circadian phase equivalent to midday.
“Sympathetic tone (circulating epinephrine and norepinephrine) had large endogenous circadian rhythms (peakto-trough amplitudes of 70% and 34% of the mean, respectively) that peaked at a circadian phase equivalent to midday.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [90]
The reactivity of blood pressure to exercise, but not postural change, is controlled by the circadian timing system, with the greatest response occurring during the biological evening.
“The reactivity of blood pressure to exercise, but not postural change, is also controlled by the circadian timing system, again with the greatest response occurring during the biological evening”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2010
The reactivity of heart rate to standardized exercise and postural changes is not influenced by the circadian timing system.
“the reactivity of heart rate to standardized exercise and postural changes is not influenced by the circadian timing system”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2010
A circadian rhythm in resting heart rate exists in healthy humans, with a broad peak during the middle of the biological day and a trough during the biological night.
“A circadian rhythm in resting heart rate has been reported by different research groups in healthy humans, with a broad peak occurring during the middle of the biological day and a trough during the biological night”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2010
The reactivity of epinephrine and norepinephrine in healthy humans to exercise is dependent on circadian phase, with two peaks: one in the biological morning and the other in the biological evening.
“The reactivity of epinephrine and norepinephrine in healthy humans to exercise is dependent on circadian phase, with two peaks: one in the biological morning and the other in the biological evening”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2010
The circadian timing system influences the reactivity of the sympathetic nervous system to behavioral stressors, including exercise and passive head-up tilt, with the largest reduction in parasympathetic markers occurring in the biological morning, corresponding to approximately 9 AM.
“The circadian timing system also influences the reactivity of the sympathetic nervous system to behavioral stressors, including exercise and passive head-up tilt, with the largest reduction in parasympathetic markers occurring in the biological morning, corresponding to approximately 9 AM”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2010
Markers of parasympathetic nervous activity display a circadian rhythm at rest in healthy humans, with peaks in the biological night and morning, and may be protective in the morning in healthy subjects at rest.
“Markers of parasympathetic nervous activity display a circadian rhythm at rest in healthy humans, with peaks in the biological night and morning, and thus may be “protective” in the morning, at least in healthy subjects at rest”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2010
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- Authors
- Scheer, F. A. J. L., Hu, K., Evoniuk, H., Kelly, E. E., Malhotra, A., Hilton, M. F., & Shea, S. A.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-08
- Volume
- 107
- Issue
- 47
- Pages
- 20541-20546
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2996667
- OpenAlex
- W2036006578
- Cited by
- 332
- References
- 52
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 23 · 2023: 28 · 2022: 28 · 2021: 16 · 2020: 18 · 2019: 22 · 2018: 20 · 2017: 20 · 2016: 12 · 2015: 23 · 2014: 18 · 2013: 25 · 2012: 14
- FWCI
- 7.57
- 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 Institutes of Health (7k24hl093218-06, 1k99hl102241-01, K99-HL102241, RR‐02635)
- National Heart, Lung, and Blood Institute (K99-HL102241, K24HL076446, K24 HL-093218, R01HL076409, P30HL101299)
- National Center for Research Resources (M01RR002635)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- circadian rhythm, circadian system, physical activity, cardiovascular function, cortisol, catecholamines, epinephrine, norepinephrine, blood pressure, cardiac vagal modulation, sympathetic nervous system, platelet aggregation, hemostasis, cardiovascular reactivity, circadian desynchrony, dim light, cardiovascular risk markers
- MeSH terms
- Adult, Blood Pressure, Body Temperature, Cardiovascular Diseases, Catecholamines, Circadian Rhythm, Female, Heart Rate, Hemostasis, Humans, Hydrocortisone, Male, Time Factors, Exercise, Likelihood Functions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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