Early Morning Attenuation of Endothelial Function in Healthy Humans
Abstract
Background— Cardiovascular events such as myocardial infarction, sudden death, and stroke have a peak incidence in the early hours after waking. The mechanisms involved in this circadian variation are not clear. Endothelial dysfunction is associated with increased risk for cardiovascular events. We tested the hypothesis that endothelial function is reduced in the early morning, around the time of waking, compared with measurements obtained both before sleep and later in the day in healthy humans. Methods and Results— We studied 30 subjects (19 men, 11 women; mean age, 41.6 years). All participants underwent polysomnography to exclude obstructive sleep apnea or other sleep disorders. Brachial artery flow–mediated endothelium-dependent vasodilation (FMD) and endothelium–independent dilation (non-FMD) were measured on 3 different occasions: before subjects went to sleep (9 pm ), the next morning immediately after waking (6 am ), and during the late morning 5 hours after waking (11 am ). All subjects had normal sleep with good sleep efficiency of 84±2%. Compared with before sleep, FMD decreased markedly in the early morning after waking and recovered by late morning (9 pm , 7.5±1%; 6 am , 4.4±0.7%; 11 am , 7.7±1%; P =0.02). Non-FMD was similar for the 3 periods of observation (9 pm , 17.3±1.6%; 6 am , 17.2±1.3%; 11 am , 18.5±1.7%). Conclusions— FMD is blunted in the early morning in healthy subjects. Decreased endothelial function in the early morning may have implications for our understanding of the morning peak in cardiac and vascular events.
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Almost all cardiovascular variables assessed at different times of day and night in humans have a day/night pattern, including blood pressure, heart rate, circulating catecholamines, blood coagulation markers, and vascular endothelial function.
“Almost all cardiovascular (CV) variables that have been assessed at different times of day and night in humans have been found to have a day/night pattern, including blood pressure (BP) (1-3), heart rate (HR) (3), circulating catecholamines (4), blood coagulation markers (5), and vascular endothelial function (6).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [6]
In humans, vascular endothelial function is relatively impaired in the morning, and therefore potentially implicated in the morning increase in adverse cardiovascular events.
“In humans, vascular endothelial function is relatively impaired in the morning (6, 123-126), and therefore potentially implicated in the morning increase in adverse CV events (127).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [6]
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References 46 · Cited by 273
- Authors
- Otto, M. E., Svatikova, A., Barretto, R. B. D. M., Santos, S., Hoffmann, M., Khandheria, B., & Somers, V.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Venue
- Circulation
- Published
- 2004-06
- Volume
- 109
- Issue
- 21
- Pages
- 2507-2510
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2066111274
- Cited by
- 273
- References
- 46
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 10 · 2023: 9 · 2022: 12 · 2021: 12 · 2020: 9 · 2019: 13 · 2018: 10 · 2017: 5 · 2016: 8 · 2015: 19 · 2014: 11 · 2013: 13 · 2012: 10
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL65176, R01HL073211, R01HL065176, HL70602, HL61560, HL-73211-01, R01HL061560)
- National Center for Research Resources (M01-RR00 585, M01RR000585)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- endothelial function, circadian rhythm, early morning, flow-mediated dilation, endothelium-independent relaxation, brachial artery, awakening, cardiovascular events, healthy volunteers
- MeSH terms
- Adult, Anthropometry, Blood Pressure, Brachial Artery, Cardiovascular Diseases, Circadian Rhythm, Electrocardiography, Endothelium, Vascular, Female, Heart Rate, Humans, Male, Middle Aged, Norepinephrine, Reference Values, Sleep, Ultrasonography, Vasodilation, Wakefulness, Polysomnography
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