Sleep Deficiency and Deprivation Leading to
Michelle Kohansieh1and Amgad N. Makaryus2
1Stern College for Women, Yeshiva University, New York, NY 10016, USA
2Department of Cardiology, North Shore-LIJ Health System, Hofstra North Shore-LIJ School of Medicine,
Nassau University Medical Center, East Meadow, NY 11554, USA
Correspondence should be addressed to Amgad N. Makaryus; email@example.com
Received November ; Revised May ; Accepted May
Academic Editor: Markus P. Schlaich
Copyright © M. Kohansieh and A. N. Makaryus. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
Sleep plays a vital role in an individual’s mental, emotional, and physiological well-being. Not only does sleep deciency lead
to neurological and psychological disorders, but also the literature has explored the adverse eects of sleep deciency on the
cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD) risk factors, such
as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep deciency and deprivation
as a cause for cardiovascular disease and cite endothelial dysfunction as a common underlying mechanism.
Sleep is an essential part of human health and well-being.
Sleep plays a vital role in an individual’s mental, emotional,
and physiological health. Not only does sleep deciency lead
to neurological and psychological disorders, but also vast
amounts of literature have explored the adverse eects of
sleep deciency on the cardiovascular system. Decreased
quantity and quality of sleep, whether due to sleep disorders
or just through lack of proper sleep patterns, have been linked
to cardiovascular disease (CVD) risk factors, such as hyper-
tension, obesity, diabetes, and dyslipidemia [–]. Studies
have shown that short durations of sleep are associated with
secondary causes of sleep deciency leading to CVD have
been well described such as obstructive sleep apnea, here we
explore the literature correlating primary sleep deciency and
deprivation as a cause for cardiovascular disease through an
underlying mechanism of endothelial dysfunction.
2. Sleep Deficiency and Deprivation:
Defining the Problem
Sleep deprivation and deciency have a high prevalence in
western societies. e National Sleep Foundation reported
that less than half (%) of all Americans receive a good
night’s sleep almost every night . According to the National
Institute of Health, sleep deciency is a broad concept that
occurs (a) if an individual does not get enough sleep (sleep
deprivation), (b) if an individual’s sleeping habits are out
of sync with the body’s natural circadian rhythm (sleeping
quantity of sleep is diminished due to a sleep disorder or
external factors . Our review will focus on four specic
variations of sleep deciency: insomnia, acute total sleep
deprivation (TSD), partial sleep deprivation (PSD), and night
Acute TSD refers to the avoidance of sleep for a period
of at least one night. PSD, or sleep restriction, refers to
the reduction in the total sleep time relative to one’s usual
baseline during a -hour period. PSD is the most common
form of sleep deprivation encountered in everyday life in
modern societies . Insomnia is dened as a predominant
associated with one or more of the following symptoms:
diculty initiating sleep, diculty maintaining sleep char-
acterized by frequent awakenings or problems returning to
sleep aer awakenings, or early morning awakenings with
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International Journal of Hypertension
Volume 2015, Article ID 615681, 5 pages
International Journal of Hypertension
follows a work schedule that is outside the typical “ to ”
business day. According to the Bureau of Labor Statistics,
millions of Americans are considered shi workers, including
doctors and nurses, pilots, bridge builders, police ocers,
customer service representatives, and commercial drivers.
rhythm, are sleep deprived, and experience frequent sleep
3. Establishing the Link between
Sleep Deficiency/Deprivation and
3.1. Endothelial Dysfunction. e endothelium is the thin
layer of cells that covers the internal surface of blood vessels,
cardiac valves, and several body cavities. ese cells play a
vital role in maintaining homeostasis by sensing changes in
hemodynamic forces and blood-borne signals. In response
to homeostatic changes, endothelial cells elicit relaxation and
contractions of the underlying vascular smooth muscle cells
releasing vasoactive substances. Among those substances,
nitric oxide (NO) plays a key role .
When an imbalance of the actions of the endothelium
toward reduced vasodilation and increased vasoconstriction
as well as increased prothrombotic properties occurs, it is said
that endothelial dysfunction is present. Arterial endothelial
dysfunction is an important event central to the pathogenesis
of atherosclerosis. Continued endothelial dysfunction con-
tributes to plaque initiation and progression .
Endothelial function can be measured in coronary arter-
ies and in the periphery by measuring vasomotor function
aer intra-arterial infusion of pharmacologic substances that
these methods is their invasive nature, which generally makes
them unsuitable for studies involving asymptomatic subjects.
For this reason, noninvasivetests of endothelial function have
been developed and are more commonly used. Flow mediated
dilation (FMD) is an ultrasound-based method that measures
arterial diameter in response to an increase in shear stress,
which causes endothelium-dependent dilatation . is
method can be applied more widely for the evaluation of
endothelial dysfunction and has been applied to patients with
3.2. Insomnia. One major study, the HUNT (Nord-
Trøndelag Health Study) tness study, has explored the
connection between insomnia and endothelial function. e
study produced negative results, providing no association
between endothelial dysfunction and insomnia. ere were
no consistent associations between the cumulative number
of insomnia symptoms and FMD. However, when the study
analyzed individual insomnia symptoms, it found that certain
symptoms might be related to endothelial dysfunction and,
interestingly, those symptoms diered by gender. Among
women, there was an inverse association of early awakenings
with endothelial function, but there was an opposite asso-
ciation for men. In addition, women who reported daytime
e HUNT study had followed earlier health studies
in Norway including the HUNT study which researched the
association between insomnia and ill health and showed that
insomnia is a signicant risk factor for myocardial infarction
. e negative results of the HUNT tness study were
not expected. It should be noted that the study had several
limitations that may have led to such results, such as a self-
selection bias and the fact that the study restricted itself to
stratication bias excluding a signicant population who may
exhibit endothelial dysfunction.
3.3. Total Sleep Deprivation. In contrast to insomnia, there is
more literature on the eects of TSD on endothelial function.
One particular study which examined cardiologists on call
for hours showed that, aer being on call, along with an
physicians had a brachial artery dilatation that did not reach
.%, and ve of them did not have any dilation at all .
is analysis attributes the dierence in endothelial function
to stress since it is traditionally accepted that mental stress
is linked to activation of the sympathetic nervous system. In
this case apparently there was a double stress: stress induced
by a lack of sleep and stress secondary to high level medical
decision making. e dierentiation between the results that
were caused due to a lack of sleep and those due to the
mental stress of being on call for a long period of time
is not clear however. Ghiadoni et al. conducted a study
investigating the link between mental stress and endothelial
function and found that brief episodes of mental stress, like
those encountered in everyday life, may cause transient (up to
a period of hours) endothelial dysfunction in healthy young
Another study by Sauvet et al., exploring the eect
of acute sleep deprivation on vascular function in twelve
healthy males, found that the endothelium-dependent and
the endothelium-independent cutaneous vascular reactivity
indices were signicantly decreased aer hours of TSD.
By contrast, heart rate, systolic blood pressure, and the nor-
malized low-frequency component of heart rate variability
(.–. Hz), a marker of sympathetic activity, increased
signicantly within hours of TSD . is same group
of researchers then conducted a follow-up study in rats.
ey found that TSD induced a reduction in endothelial-
dependent vasodilation .
3.4. Partial Sleep Deprivation. e relationship between PSD
and endothelial dysfunction has received more attention than
TSD and insomnia. In the several studies performed in the
literature, PSD has consistently been linked to decreased
vasodilation. Covassin et al. conducted a study on healthy
subjects who underwent a -day inpatient protocol consist-
ing of a three-day acclimation period, eight days of either
sleep deprivation or normal sleep, and four days of recovery.
sleep occurred, FMD decreased during the experimental
phase in the sleep deprived group (. ±.% versus . ±
.%, 𝑃 = 0.008), while it remained unchanged in controls
(. ±% versus . ±.%, 𝑃 = 0.109). A study
International Journal of Hypertension
conducted by Pugh et al. demonstrated that, compared to
the control group who received three nights of full sleep and
did not exhibit any changes in their endothelial function, the
participants who received three nights of PSD ( hours of
aer the second night of sleep restriction but, interestingly,
recovered aer the third night of PSD . Dettoni et al.
males. ey found a reduction in the maximum endothelial-
dependent venodilation ( ± versus ±%) .
3.5. Shi Work. Compared to the other sleep habits that
were mentioned, shi work has received the most attention
when considering its eects on endothelial function. One
showed that aer they worked sequential night shis the
FMD was signicantly decreased from baseline FMD taken
aer one regular workday .Suessenbacheretal.com-
pared male shi workers with male nonshi workers
from a glass manufacturer using the EndoPAT technique
to determine peripheral arterial tone (PAT). ey found
that, despite a greater percentage of regular physical activity
among the shi workers (. versus .%), shi work was
associated with a reduced PAT index compared to working
only on the day shi (PAT index . ±. versus . ±.)
. While physical activity has been associated with better
endothelial function , this study suggested that the eects
of sleep deprivation override the benets of physical activity
on vascular health. Wehrens et al. studied the long term
eects of shi work. eir study compared the dierence in
FMD aer two groups (shi workers compared to nonshi
workers) were put through sleep deprivation and recovery
sleep in identical laboratory settings. Aer correcting for the
dierence in body mass index (BMI), there was a trend for
lower %FMD (𝑃 = 0.08) observed among shi workers
compared to nonshi workers . Amir et al. conducted
a study that had results consistent with this trend. irty
healthy physicians who had worked night shis for an average
of ± years had their endothelial function examined aer
a regular workday as the baseline and aer a continuous
a signicant decrease in FMD aer shi work compared with
baseline measurements (. ±.% versus . ±.%). e
authors more importantly also noted that FMD decreased
signicantly in all subsets except in physicians with a shorter
(< years) history of night shis. In these physicians with
the shorter history, the change in FMD aer the shi was
independently related to the length of shi work history .
ese results were consistent with those found in the previous
be long term implications of shi work on vascular function.
4. Mechanisms of Endothelial Dysfunction
Caused by Sleep Deprivation (Figure 1)
4.1. Sympathetic Activation. Sympathetic overactivity has
been a proposed explanation to the link that is seen between
sleep deprivation and endothelial dysfunction. Dettoni et
dependent venodilation found in healthy males aer PSD to
an increase in sympathetic activity as the participants also
experienced an increase in percent low-frequency ( ±
versus ±) and a decrease in percent high-frequency ( ±
versus ±) components of heart rate variability, increase
in low-frequency band of blood pressure variability, and an
increase in their serum norepinephrine (119 ± 46 versus
162 ± 58 ng/mL) .
Other studies, however, have rejected the association of
sleep deprivation and sympathetic activation. Of the nine
studies that link sleep deciency and endothelial function
mentioned in our review, three studies had a signicant
change in blood pressure, four studies did not investigate
blood pressure, and two studies saw no dierence in blood
pressure. Studies that did not show a change in blood
pressure, or did show a change but the change came aer
evidence of endothelial dysfunction, argue that endothelial
dysfunction may not be due to increased sympathetic activity
of being awake for a prolonged period of time but rather due
to another factor. In a study on rats by Sauvet et al., they
concluded that while sleep deprivation did decrease endothe-
lial vasodilation, it was not due to changes in blood pres-
sure and was independent of sympathetic activity because
it was still evident aer pharmacological sympathectomy.
Rather, it appears to be associated with NO synthase and
cyclooxygenase pathway alterations, specically, a decrease
in the activity of those pathways . e authors, however,
mentioned that a persistent increase in sympathetic activity
could lead to endothelial dysfunction. is was supported by
studies that have shown that subjects with a greater history
of night shi work are more likely to have more endothelial
dysfunction than subjects who rarely took the night shi
and therefore argue the direct causal eect of sympathetic
4.2.eRoleofNitricOxide.Endothelial dysfunction is
lead to disruption of vascular homeostasis. NO is responsible
for the modulation of vascular dilator tone, regulation of local
cell growth, and protection of blood vessels from injurious
consequences of platelets and cells circulating in blood. NO
therefore plays a crucial role in normal endothelial function
. In the study conducted by Suessenbacher et al. on
female nurses, in addition to the fact that aer working
sequential night shis endothelial function was impaired,
the results also showed that mono-nitrogen oxides (NO𝑥)
were also signicantly decreased aer sequential night shis
compared with the baseline measurements (from . ±
. mmol/dL to . ±. mmol/dL, 𝑃 = 0.033), although,
in the end, there was no correlation between changes in NO𝑥
and FMD before and aer sequential night shis (𝑟=
−0.218,𝑃 = 0.356). In rats, TSD was found to lead to
It is possible that the reduction in the bioavailability
of NO in these sleep deprivation cases may be due to the
decreased expression of NO synthase (eNOS) by endothelial
[,]. Altered signaling is also a possibility. However, when
International Journal of Hypertension
Insomnia Shi work
Total sleep deprivation Partial sleep deprivation
Increased level of coagulability
decreased levels of
considering sleep deciency, oxidative damage seems to be
the mechanism. Oxidative stress occurs when there is an
imbalance between oxidizing free radicals and antioxidant
defenses. Free radicals or reactive oxygen species (ROS) such
as O2−are quick to react with and inactivate NO. us, vas-
cular oxidative stress can lead to a decrease in NO bioavail-
ability. Under normal physiological conditions, endogenous
antioxidant defenses minimize this interaction, thus allowing
tion has been linked to increased uncompensated oxidative
stress in peripheral tissues; however, a positive nding shows
that recovery sleep can actually restore antioxidant activities
. A more recent study found that sleep deprivation does
aect antioxidant activity by producing and imbalance in the
oxidizing of the spleen cells. While the mechanisms of the
cytoxic-like eects of sleep deprivation are likely “related to
dysfunction in mitochondrial metabolism and vulnerability
in cell signaling pathways,” the exact mechanisms are not
understood and require further study .
While there is evidence of an association between endothelial
dysfunction and sleep deprivation, it still remains to be
evaluated if sleep deprivation is a cause of or is associated with
increased risk of CVD. However, endothelial dysfunction
is an established independent risk factor for cardiovascular
disease. erefore, many of the factors that link endothelial
dysfunction to cardiovascular disease are likely a result of the
negative eects of sleep deciency and deprivation. Further
research in the area of sleep deprivation/deciency is needed
especially its relation to cardiovascular disease.
Conflict of Interests
e authors declare that there is no conict of interests
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