Shift work and cardiovascular disease – pathways from circadian stress to
by Sampsa Puttonen, PhD,1 Mikko Härmä, MD, PhD,1 Christer Hublin, MD, PhD 1
Puttonen S, Härmä M, Hublin C. Shift work and cardiovascular disease – pathways from circadian stress to
morbidity. Scand J Work Environ Health. 2010;36(2):96–108.
In order to establish a causal relation between shift work and cardiovascular disease (CVD), we need to verify
the pathways from the former to the latter. This paper aims to review the current knowledge of the mechanisms
between shift work and CVD. Shift work can increase the risk of CVD by several interrelated psychosocial,
behavioral, and physiological mechanisms. The psychosocial mechanisms relate to difficulties in controlling
working hours, decreased work–life balance, and poor recovery following work. The most probable behavioral
changes are weight gain and smoking. The plausible physiological and biological mechanisms are related to the
activation of the autonomic nervous system, inflammation, changed lipid and glucose metabolism, and related
changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The data provide evidence for
possible disease mechanisms between shift work and CVD, but compelling evidence on any specific mechanism
Key terms CHD; coronary heart disease; CHD; CVD; literature review; working hour.
1 Finnish Institute of Occupational Health, Helsinki, Finland.
Correspondence to: Sampsa Puttonen, Centre of Expertise on Human Factors at Work, Finnish Institute of Occupational Health,
Topeliuksenkatu 41a A, FI-00250 Helsinki, Finland. [E-mail: email@example.com]
Despite two decades of reviews, there is still no con-
sistent evidence that shift work increases the risk of
cardiovascular disease (CVD) (1–3). Most epidemio-
logic research on the area has focused on the risk for
coronary heart disease (CHD). In the latest review based
on 16 studies, Frost and coworkers (3) concluded there
was limited evidence for a causal relationship between
shift work and ischemic heart disease. The term “limited
evidence” (3) refers to the fact that a casual relationship
between the exposure and disease is possible but could
be explained by chance, bias, or confounding.
The review by Frost et al (3) showed a stronger
association between shift work and morbidity than
mortality, suggesting that selection out of shift work or,
for example, the use of occupational health screening
could weaken the association with mortality. Moreover,
CVD is most common among the elderly who are no
longer exposed to work-related risk factors of CVD. In a
13-year follow-up study of the Helsinki Heart Study, the
relative risk of CHD among shift workers was 1.59 after
5 years. After 13 years, when most of the workers were
retired, the risk had decreased to 1.34 (4). The somewhat
inconsistent epidemiologic evidence on the association
between shift work and CVD is mostly due to common
problems in exposure assessment and the selection of
a proper control group. Inconsistencies also arise from
primary, secondary, and tertiary selection and some may
be the result of controlling statistically for the pathways
in addition to confounders (5).
In order to interpret the epidemiological data cor-
rectly, it is necessary to understand the pathways and
possible mechanisms mediating the effects of shift work
on CVD. We are not aware of any recent reviews on the
mechanisms linking shift work to CVD. Ten years ago,
Bøggild & Knutsson (1) concluded that there are differ-
ent but interrelated pathways that may lead from shift
work to disease in general, namely: mismatch of circa-
dian rhythms, social disruption, behavioral changes, and
changes in the biomarkers of atherosclerosis. During
more recent years, the literature on all four of these path-
ways has grown considerably. In addition to new studies
on biomarkers of atherosclerosis, direct evidence on the
association between shift work and atherosclerosis is
also emerging (6, 7).
This narrative review aimed to discuss the current
knowledge on the different pathways from shift work
to CVD, which include three major categories: CHD,
cerebrovascular disease, and peripheral vascular disease.
Our focus was on the pathways related to the athero-
sclerotic manifestations of the CVD. The review was
based on a model where the circadian stress due to work-
ing in shifts can induce three different major pathways
from shift work to the CVD: a behavioral, psychosocial,
and physiological one (figure 1).
Shift work is defined as either work at changing hours
of the day (eg, morning, afternoon, and night shift) or
work at constant but unusual hours of the day (eg, per-
manent afternoon shift or permanent night shift) (8). CVD
are a group of disorders of the heart and blood vessels
(9). The term circadian stress refers to the physiologi-
cal, behavioral, and psychosocial consequences related
to the disturbances of the human circadian rhythm (eg
the sleep–wakefulness rhythm). The timing of 24-hour
operations is the major challenge in organizing shift work
as well as being one of the major causes of circadian
stress. However, shift work may or may not include night
work and, besides night work, other unusual or irregular
working hours may also cause circadian stress (eg, early
morning work). Work stress refers to those aspects of
work design, organization, and management, and their
social and organizational contexts, that have the potential
to cause harm to employee health (10).
Psychosocial stress as a pathway
There is evidence that both socioeconomic status and
work stress are risk factors for CVD (11, 12). A system-
atic review and meta-analysis by Kivimäki et al (12)
concluded that work stress, defined by three prevalent
work stress models, was associated with a 50% excess
risk of CHD according to prospective studies. Although
the individual studies on job strain are partly incon-
sistent, an association between low job control and
the risk of ischemic heart disease has been repeatedly
found (13, 14). Since shift work is associated with both (13, 14). Since shift work is associated with both
socioeconomic status and psychosocial factors at work
(15), the independency of shift work as a risk factor for
CVD has been questioned. Despite having controlled
for differences in work demands and work stress, some
prospective studies have found a significant association
between shift work and CVD (16–18). Shift work can
act as a specific “circadian” psychosocial stress factor
in several ways. First, shift work may increase psy-
chosocial stress due to inflexibly organized shifts that
leave limited possibilities for employees to influence
their working hours. Second, shift work is described
as comprising “unsocial” working hours since it may
decrease the work–life balance due to possible vari-
ability and/or unsocial timing of leisure time. Finally,
shift work may increase the perception of insufficient
recovery from work.
Shift work and work stress
In relation to the job strain model (19), shift work has
been associated with lower job control compared to day
work, while work demands and social support do not
seem to differ (15, 20, 21). Based on a random sample
of Danish employees, conflicts at work and low decision
latitude were higher among all groups of shift com-
pared to day workers (15). Differences in work stress
between shift and day workers vary between occupa-
tions, but there may also be differences within occupa-
tions. In eldercare, for example, women in fixed non-day
Figure 1. Model for pathways from shift work to
Figure 1. Model for pathways from shift work to coronary heart disease.
• work stress
• recovery from
OTHER DISEASE CONDITIONS
• metabolic syndrome
• type II diabetes
• blood coagulation
• cardiac autonomic
• blood pressure
• sleep quality and
• weight gain
• physical inactivity
shifts were more often exposed to low job control and
decreased support from supervisors and had a higher risk
of physical and psychological violence (22). Karasek’s
job control factor does not include work-time control or
control over work scheduling. However, perceived con-
trol over working hours, which has been shown to pre-
dict decreased sickness absence and a good subjective
health (23), correlates highly with job control (24).
Another commonly used work stress model, the
effort–reward imbalance model of Siegrist et al (25)
focuses on a person’s perception of the balance between
his or her efforts at work and the rewards received. The
different aspects of working hours are not directly cov-
ered by the model, but both indicators of effort–reward
imbalance (ie, a need for control and approval and unfa-
vorable effort–reward ratio) are more prevalent among
shift than day workers (17). However, in addition to the
suggested mediating effects of effort–reward imbalance
at work for CVD risk factors, including hypertension
and atherogenic lipids, shift work has also direct effects
on these risk factors (17).
Shift work, work–life balance, and recovery
Shift work and irregular working hours can disturb
the work–life balance. Even after adjustment for work
stress, working in shifts decreases the perceived balance
between work and social life (26–29). For example,
compared to day work, baseline shift work was associ-
ated with higher work–home interference over time in
the Maastricht cohort study (28).
A good work–life balance means an appropriate
mixture of work and recovery. A high need for recovery
predicted an increased incidence of self-reported CVD
in a 2.5-year follow-up among healthy employees at
baseline (30). Similarly, employees who seldom recov-
ered from work during free weekends had an elevated
risk of death due to heart disease even after controlling
for age, gender, and 16 risk factors, including fatigue,
lack of energy, and job stress (31). Shift work is related
to a greater need for recovery (32, 33). Working hours
define the time left for social activity and sleep that
may be used for recovery either during the work (work
breaks) or afterwards (leisure time). Based on this, the
effort–recovery stress model (34) suggests that the nega-
tive consequences of work hours on health depend on
the possibilities for recovery during and after work.
In conclusion, shift work may induce psychosocial
stress through (i) greater difficulties to control personal
working hours, (ii) decreased work–life balance, and
(iii) insufficient recovery. Although the basic differences
in work stress between day and shift workers may at
least partly mediate the association between shift work
and the risk of heart disease, shift work also includes
specific psychosocial stress factors relevant for CVD.
Behavioral stress as a pathway
Shift work is associated with circadian disruption that also
affects behavior. One of the most notable changes can be
observed in sleep–wake patterns; from time to time, the
main sleep period is temporally displaced and the worker
suffers from sleep debt, insomnia, and/or excessive sleep-
iness. This is most notable in night shifts but also seen in
early-morning and late-evening shifts. Other aspects of
behavior which may change are smoking, consumption
of alcohol, dietary intake, and physical exercise.
Sleep quality and length
Epidemiologic studies since the 1960s have shown that
sleep duration is associated with a risk of mortality. The
association is U-shaped, with the lowest risk in those
sleeping 7 hours (about the average length in the general
population). In a recent meta-analysis (35), the pooled
relative risk (based on 16 studies with sufficient data) for
all-cause mortality for short sleep duration (<7 hours)
was significantly increased (10% higher compared to
those sleeping 7–8 hours). However, cardiovascular-
related mortality was non-significantly increased (6%).
Sleepiness is over-represented in shift/night workers.
In many studies, a majority of shift workers admit to
having experienced involuntary sleep on the night shift,
whereas this is rare in day-oriented shifts (36). Insuf-
ficient sleep and sleepiness activate the sympathetic
nervous system and lead to increases in blood pressure
and heart rate (37). A study among young, healthy indi-
viduals found that only 6 consecutive nights of bedtime
restricted to 4 hours per night increased the activity of
the sympathetic nervous system and evening cortisol
concentrations and decreased glucose tolerance (38). On
the other hand, sleep deprivation increases hunger and
decreases leptin, a factor inhibiting hunger (39). Experi-
mental short-term sleep deprivation also increases the
peripheral circulation of leukocytes, interleukins, and
C-reactive protein, the last of which is a predictor of the
risk of stroke and myocardial infarction (40–42).
Shortened or disturbed sleep is among the most com-
mon health-related effects of shift work (43, 44). The
effects on sleep length depend on whether the shifts are
permanent or rotating, in the latter case the speed and
direction of rotation have an impact. In a meta-analytic
review, based on 36 primary studies, Pilcher et al (45)
concluded that permanent night shifts result in a decrease
in the length of sleep (mean 6.6 hours), whereas perma-
nent evening shifts result in an increase (mean 7.6 hours).
Furthermore, the shifts within rotating schedules followed
the same pattern (mean night 5.9 and evening 8.0 hours),
with the addition of morning shifts having a moderate
detrimental effect on sleep length (mean 6.6 hours).
The International Classification of Sleep Disorders (46)
includes criteria for “shift work sleep disorder”. In one
of the few epidemiological studies on this subject, 8% of
shift workers and 14% of nighttime workers were found
to suffer from the disorder (47). Still, shift work does not
appear to be a major source of insomnia and the level of
sleep complaints bear no resemblance to those seen in
insomniac patients (36). This shift work sleep disorder
study showed very few differences between shift and day
workers; only “too little sleep” and “nodding off at work”
were higher among shift compared to day workers.
The association between smoking and shift work has
been the subject of much debate. Many studies have
shown that smoking is more prevalent among shift than
daytime workers, but most studies have been cross-
sectional or queried about smoking only once. Bøggild
& Knutsson (1) concluded that, in seven “positive”
studies (out of 13), the excess prevalence of smok-
ing was 10–40%. The systematic review of Frost et al
(3) was based on 14 studies, of which six reported on
smoking and found that it was generally more frequent
among shift workers. In recent studies with information
on smoking, results have been mixed, indicating either
no increase (48), a slight increase [3.9% (49) and about
10% (50)], or a significant increase (7) of smoking
among shift workers.
It has also been suggested that smoking should be
regarded as a mediator of CVD, as it may be a way ofCVD, as it may be a way of
staying awake during the night shift and, therefore,
could be regarded as a causal chain variable (51). Pre-
employment smoking has been controlled for only in
two case–control studies (3). A two-year follow-up
study showed a significantly increased risk (46%) of
starting smoking among shift compared to day work-
ers (52). In a one year follow-up study, shift work was
quite strongly associated both with smoking status and
starting to smoke at a later date; it was concluded that
smoking status should not solely be treated as a mediator
but also considered a confounder (53).
, as it may be a way of
There have been some studies on dietary changes in
association with shift work. In a Swedish study, Lenne-
rnäs et al (54) found that working two and three shifts
affected the circadian distribution of food and coffee
consumption but not the overall 24-hour consumption.
In a Japanese study (55), there were no significant dif-
ferences in nutrient intake between fixed daytime and
non-night shift workers. On the other hand, energy
intake was highest during the night shift particularly
among middle-aged workers.
Studies assessing lipids in shift workers have had vari-
able results. Of 16 studies, 5 showed increased cholesterol
levels; 3 of these were prospective studies (1). In a fol-
low-up study by Morikawa et al (56), the increases in total
cholesterol were similar among day and shift workers.
On the contrary, a methodologically similar 14-year fol-
low-up study found a higher increase in total cholesterol
among Japanese shift workers (57). In an Italian male
cohort with repeated health examinations, night work-
ers had significantly higher total cholesterol than their
daytime colleagues (58). Regarding triglycerides, higher
values were found among shift workers in 4 of 12 studies
(1). Similarly, more recent studies have shown variable
results [no difference (59) or elevated (60)].
Shift work may also influence weight gain through
reduced sleep. A meta-analysis of 26 cross-sectional
studies indicated an increased obesity among those with
shorter sleep times (mostly ≤5 hours (61). However,
in their critical review (62), Marshall and colleagues
concluded that it was unclear from the available adult
epidemiological literature if short sleep and obesity or
weight gain are associated. Some studies have indicated
that starting shift work may be related to gains in body
weight (3). Suwazono et al (63) reported a significantly
increased risk (1.14) of ≥5% weight gain among shift
compared to daytime workers. Similarly, Morikawa et
al (56) found a significant increase in body mass index
(around 1 kg/m2) among those working continuously in
shifts and those changing from daytime to shift work.
In the aforementioned Italian male cohort with repeated
health examinations, night workers had significantly
higher body mass index than daytime workers (58).
Other behavioral aspects
There are no consistent results on differences in alcohol
consumption or exercise between shift workers and the
general population (1). Recent studies have shown no
significant difference in either case among men (7, 49);
among women, a significant decrease in physical activ-
ity and a non-significant decrease in alcohol consump-
tion have been reported (7).
Physiological stress and reactions as a pathway
In order to establish a causal relation between shift work
and CVD, we need to point out the specific underlying
physiological and biological mechanisms that influence
the disease process at different phases. We have summed
up the results of studies using established independent
biochemical or physiological risk factors of CVD but
also incorporated studies using other suggested markers.
By doing this, we have provided a more comprehensive
picture of the evidence and can point to the need for
further research. The examined mechanisms and risk
factors of CVD range from inflammation, blood coagu-
lation, physiological and biological stress mediators
(autonomic nervous system and hypothalamic-pituitary-
adrenal axis, which control the body’s levels of cortisol
and catecholamine), and blood pressure to disease condi-
tions such as hypertension and type II diabetes.
Inflammation plays a critical role in the atherosclerotic
process, all stages of atheroma formation, and CHD
(64). Several markers of inflammation have been associ-
ated with CVD risk. However, only a small number of
studies have tested whether the mechanism is active in
the observed shift work–CVD association. High sensi-
tive C-reactive protein, leucosyte count, lymphosyte,
and NK-cell activity have received some interest in shift
work studies. Sookoian et al (60) and Nishitani et al (65)
reported an increased leucocyte count among rotating
shift compared to daytime workers. In addition, 3-shift
work has been associated with reduced T-lymphosyte
function (66, 67). In more recent studies, NK-cell activ-
ity was lower among shift compared to daytime workers;
among shift workers, activity was also lower during
night as compared to day shifts (68, 69).
Homocysteiene and blood coagulation
Plasma homocysteine is an independent risk factor for
atherosclerosis and CVD (70) and potentially influences
several risk mechanisms of CVD, including endothelial
dysfunction, oxidative stress, and atherogenic inflam-
mation (71). At least three cross-sectional studies have
examined the association between homocysteine and
shift work. Homocysteine levels have been reported
to be increased in shift work, but no difference has
been found in the prevalence of hyperhomocystein-
emia [defined as levels exceeding the normal value
(>15 mmol/l)] (72, 73). The level of homocysteine was
found to be almost twice as high among male shift com-
pared to day workers (73), while another study reported
significantly increased levels only for older shift work-
ing men with sleep complaints (74). The current evi-
dence suggests that there may be some association
between shift work and homocysteine, but the evidence
is thin and far from conclusive. The same holds true for
microalbuminuria, which is a risk marker for arterial
thromboembolism (75) and a predictor of CVD mortality
and cardiac events (76). The association between shift
work and albumin excretion has been examined in one
study, suggesting that shift workers may have increased
excretion compared to day workers (77). Similar levels
of fibrinogen among day and shift workers have been
reported (78), while another study on plasminogen acti-
vator and tissue plasminogen activator inhibitor showed
lower fluctuations among those working shifts both dur-
ing the day and night, suggesting some deficiency in the
diurnal variation of blood coagulability (79).
Cardiac autonomic function
Shift work may influence acutely autonomic function,
increasing cardiac sympathetic and decreasing para-
sympathetic activity during work and sleep following
a work period. Over 15 studies using field measures
have reported lower levels of parasympathetic modula-
tion of heart rate variability or increased sympathetic
activity in shift work (for example 68, 80–84). Others
have reported that nighttime work is associated with
reduced cardiac sympathetic modulation (81). Shift
work may predispose individuals also to prolongation
of QT intervals corrected for heart rate (QTc) (85),
indicating a possible pro-arrhythmic potential of shift
work. Indeed, a follow-up study of employees starting
their work indicated that shift workers had increased
frequency of ventricular extrasystoles, which correlated
with the number of nights worked (86).
Cortisol and catecholamine
There is relatively little evidence supporting the hypoth-
esis that cortisol would be directly associated with the
development of CVD. However, cortisol and catechol-
amines may influence stress-induced heart disease (87).
Studies have demonstrated that shift work may acutely
alter the regulation of cortisol (83, 88–91). Typically,
studies have explored how cortisol secretion alters dur-
ing shift work and cortisol measures have been used as
an indicator of adaptation to shift work, rather than as
a possible health risk factor as such. We could not find
any studies on the possible enduring effects of shift work
on cortisol secretion. Disturbed cortisol secretion and/or
altered timing may influence health risk factors such as
the development of central obesity.
Little is known about the relation between shift work
and catecholamines. The simulated shift work study of
Boucsein et al (92) found that adrenalin and noradrena-
lin excretion rates were significantly higher under day
compared to night shifts, and lower during sleep com-
pared to work. In the study of Theorell et al (93), clear
fluctuations in the diurnal pattern of catecholamine
excretion during and after night work were observed.
Catecholamine secretion shows a distinct circadian
variation and the timing of sample collection is critical
in shift work studies. Therefore, it is possible that the
observed changes in catecholamine levels may reflect
the circadian phase differences, which makes it difficult
to interpret the findings in many cases.
Atherosclerosis and other preceding disease conditions
Atherosclerosis. Up to now, two studies have explored
the association of shift work with the atherosclerotic
process. These studies have used ultrasonic measures to
estimate the level of subclinical atherosclerosis of the
carotid intima media. Haupt and colleagues (6) reported
an increased risk among shift workers in a sample of
participants ≥45 years. A similar positive association for
males was found in a study focusing on younger day and
shift workers (24–39 years old) (7).
Endothelial dysfunction is an early finding and
marker in the development of atherosclerosis. Brachial
artery endothelial function was acutely reduced after a
24-hour shift (94). The greatest decrease in flow-medi-
ated dilation was observed among participants with a
longer history of night shift duty.
Type II diabetes. At least six studies have looked at the
association between shift work and diabetes (95–100).
Five of them have been cohort studies of type II diabetes
incidence with follow-up periods ranging from 4–10
years; one study is on the mortality risk due to diabetes.
Two reports of the nurses’ health study (95, 96), with
partially overlapping data, concluded that shift work
predicts a higher incidence of type II diabetes, with an
increasing risk as a function of exposure to irregular
working hours; the study also found that obesity may
mediate the effect of shift work on diabetes risk. A
Swedish study with male participants found a positive
association between the number of years worked in shifts
and mortality due to diabetes (97), while Kawakami et al
(98) did not find any significant excess risk of incidence
of diabetes in shift work. Two studies that used glycated
hemoglobin and/or medication as the indicator of diabe-
tes status, reported both a non-significant trend towards
an increased risk (99) and an increased multivariate risk
of diabetes in shift work (100).
Metabolic syndrome (MetS). MetS, a risk factor of CVD,
is a clustering of cardiac health risk factors such as
insulin resistance, hypertension, cholesterol abnormali-
ties, and central obesity (101). Existing cross-sectional
studies have either looked at the association between
shift work and components of the MetS (58, 59, 102,
103) or the prevalence of MetS according to a standard
formulation of the syndrome (60, 104). A general con-
clusion of the studies is that shift work has relatively
consistent associations with individual risk factors of
MetS and perhaps a more consistent association when
the syndrome is considered as a whole. In addition,
recent prospective cohort studies that used international
formulations of the MetS have added to this evidence by
showing that shift work increases the risk of incidence of
MetS. In these studies, the relative risk in shift work has
varied from 1.5–5.0 (105, 106, 107) suggesting a causal
relationship between night shift work and the develop-
ment of MetS. International formulations – such as those
of the National Cholesterol Education Program’s Adult National Cholesterol Education Program’s Adult
Treatment Panel III (NCEP-ATP III), the International (NCEP-ATP III), the International
Diabetes Federation (IDF), and the European �roup for
the study of Insulin Resistance (E�IR) – use different
criteria for defining MetS. This may also have some
impact on the findings. For example, Esquirol et al
(104) used both the NCEP-ATPIII and IDF criteria and
reported that shift work was associated with NCEP-
ATPIII MetS but not with IDF MetS, a formulation
which emphasizes more abdominal obesity. The compa-
rability between studies would be facilitated if standard
and multiple definitions of MetS were used.
European �roup for
(E�IR) – use different
Blood pressure and hypertension. Studies have examined
the role of shift work in resting blood pressure levels and
daily blood pressure in field circumstances, and whether
shift work may influence the circadian profile of blood
pressure. Cross-sectional epidemiological studies do
not suggest a significant association between shift work
and blood pressure. Studies have reported similar levels
of blood pressure in shift and day workers (58, 59, 85,
104, 108), while in some studies the former have had
significantly higher blood pressure levels than day work-
ers (60, 109). When changes in blood pressure levels
are considered, a fairly similar picture emerges: some
longitudinal studies have suggested that rotating shift
work is a risk factor for an increase in blood pressure
(110, 111), while others have found no effect of shift
work on blood pressure increment (56, 112, 113).
Hypertension has been found to be more prevalent
among shift compared to day workers (114) or among
shift workers only in a certain age group (40–49 years
old) (103). In the study by Morikawa et al (115), a higher
risk of incident hypertension among shift workers was
evident only in younger participants, while among the
older participants a high risk of hypertension was found
for those who changed from shift to day work during the
follow-up. Furthermore, longer exposure to shift work
has been reported to predict the onset of hypertension
among males >30 years old (102); in the same study,
shift work was suggested to be associated inversely with
hypertension among young women <30 years of age.
Finally, shift work has been shown to predict the onset
of hypertension among male workers (116) as well as the
progression from mild-to-severe hypertension (117).
Shift work may exert transient and long-term effects
on circadian blood pressure control seen as the change
from a “dipping” to “non-dipping” pattern in which the
normally observed nocturnal decrease in blood pressure
during sleep is impaired. In a study by Yamasaki et al
(118), shift workers had a smaller drop in the systolic
blood pressure during sleep than day workers, and they
were more often categorized as “non-dippers”. Shift
work has also been associated with higher 24-hour blood
pressure levels (119, 120), while the risk of non-dipper
status yielded mixed results. The mean systolic blood
pressure during a 24-hour measurement has been found
to be higher among shift than day workers (110). In a
24-hour monitoring study (121), blood pressure was
higher during daytime sleep than sleep that occurred at
night, a finding that may point to non-dipping phenom-
ena but may also reflect the circadian variation of blood
pressure. Kitamura et al (122) reported a transient effect
of shift work on dipping at the beginning of night shift
work. This was reversed to a dipping pattern after four
days of work.
The reviewed data showed mixed results for blood
pressure levels and longitudinal increases in blood pres-
sure in shift work. There appears to be limited evidence
suggesting that shift work may acutely increase 24-hour
blood pressure and have transient and long-term effects
on dipper-status. In addition, whether shift work can
increase the risk of hypertension needs to clarifed in
additional follow-up studies. If shift workers, however,
develop higher systolic blood pressure levels than day
workers, it entails a high CHD risk (113). In the future,
the role of treatment of hypertension should also be
better taken into account. We do not know, for example,
about the possible effects of blood pressure medica-
tion in many of the previous studies. Moreover, it is
recommended to treat the use of such medication as an
outcome measure in shift work studies, as is currently
being done in studies of MetS risk.
During the last two decades, a high number of epide-
miologic studies have investigated the evidence on the
relationship between shift work and CVD. Although
epidemiologic data have grown, the lack of evidence-
based mechanisms from shift work to CVD has made
the interpretation and analysis of such data difficult. The
present evidence points to several possible pathways
from shift work to CVD. Although evidence on the
strength of any individual mechanism is still limited,
the number of studies on different pathways has been
increasing relatively fast during the last ten years. Also,
studies on essential mechanisms such as atheroscle-
rotic process have gained support (6, 7). Several of the
biomarkers related to shift work are also related to the
atherosclerotic process: inflammation, increased blood
cholesterol, homocystein, and albumin levels, in addi-
tion to the possible deficiencies in endothelial function
and blood coagulation.
The mechanisms by which shift work could be a
risk factor for CVD range from the effect of varying
working hours to the circadian body functions, but
shift work also interferes with the social and domestic
life. Besides changing the rhythm of work, shift work
changes simultaneously the behavioral rhythms in
sleep, activity, and nutrition. We therefore conclude
that there is sufficient evidence for possible disease
mechanisms from shift work to CVD, but strong evi-
dence on any specific plausible mechanism is missing.
Shift work could increase the risk of CVD by several
psychosocial, behavioral, and physiological mecha-
nisms. The different pathways are interrelated and may
also lead to other metabolic diseases by increasing the
risk for atherosclerosis, metabolic syndrome, and type
There are several reasons for preferring a narrative as
opposed to systematic review. First, the area covered by
our review is large and the relevant mechanisms include
dozens of variables to be evaluated. Second, many of
the variables have been little studied and methodologi-
cally good studies are quite scarce (eg, long follow-up
studies with large populations and adequate control
of confounders). Third, probably largely because of
variable methodology, the results of different studies
are often contradictory. Consequently, we have chosen
the narrative form and tried to emphasize the results of
methodologically strong studies.
We conclude that there is evidence that shift work can
induce psychosocial circadian stress due to a lack of
control over working hours, problems in the work–life
balance, and decreases in perceived recovery. It is obvi-
ous that shift systems vary according to their psychoso-
cial effects, with some shift systems suiting even better
to personal time constraints than others. Job control is
a key element of work stress in several stress concepts.
Since both job control and the perception of sufficient
recovery after work are independently related with CVD
(12–14, 31), it is quite possible that shift work could
increase the risk for CVD through its psychosocial stress
Poor job control, work–life imbalance, and insuffi-
cient recovery can further induce behavioral and physi-
ological stress reactions. Due to psychosocial stress
factors, shift workers may sleep less, start smoking,
and develop unhealthy eating habits. Psychosocial and
behavioral stress could trigger the physiological stress
reactions linking the psychosocial stress to the patho-
physiological mechanisms of CVD.
Both short sleep and insomnia have been reported to
increase the risk for CVD (123, 124). Although sleep-
ing <7 hours is related to the risk of total mortality, this
does not seem to be mediated through CVD (35). It is
possible that the mean sleep length of shift workers is
not significantly reduced over a longer period. The sleep
problems among shift workers also seem to be milder
than among insomniacs (36, 125). �enerally, sleep qual-
ity is not an independent risk factor of a health outcome
(risk of mortality) if sleep length is taken into account
(126). So far, there is limited evidence to support the
view that reduced quantity or quality of sleep (per se)
would be a major pathway to affect the risk of CVD in
shift work, but they might contribute to adverse physi-
ologic changes via intermittent excessive sleepiness.
There is evidence to suggest that smoking is more
prevalent among shift than daytime workers, and if this
is confirmed in future studies this could be one possible
pathway affecting CVD risk. The situation is similar
regarding serum lipids. There is more evidence on the
risk of weight gain among shift workers, and at present
this seems to be the most verified of the possible behav-
ioral pathways from shift work to CVD.
Physiological stress reactions
CVD develops over a long period with physical changes
beginning decades before the disease manifests itself;
some of the health hazards of shift work may remain
undetected when a disease condition is used as an end-
point, as employees may, for example, change to day
work when the first symptoms of CVD occur. Therefore
it is important to focus on the mechanisms of the sub-
When summing up the evidence on the findings of
biological and physiological risk factors in the shift
work–CVD association, several conclusions arise. Look-
ing at studies using the reviewed individual biological
or physiological risk factors of CVD, it is clear that
none of these possible mechanisms receive strong sup-
port at the moment. This is partially due to the fact that
biological markers of immune function, blood coagula-
tion, and oxidative stress have been rarely studied. One
reason for the low number of epidemiologic studies is
that the data have been obtained from regular physical
health check-ups with standard sets of measures. There
are, however, studies (usually with smaller numbers
of participants) providing important additional knowl-
edge on new biological and physiological risk factors.
Regarding individual factors, there is some evidence
suggesting that inflammation may serve as a pathophysi-
ological pathway. Also homocysteine has received some
evidence. The main stress mediators, hypothalamic-
pituitary-adrenal axis and autonomic nervous system,
have been widely studied with regard to shift work.
These studies have concluded that shift work has acute
effects on the stress mediators’ levels and diurnal varia-
tion, thus potentially increasing harmful allostatic load.
However, this evidence is only indirect, and we could
not find any studies on longitudinal effects. In future,
it would be important to study the effects of shift work
on, for example, cortisol and heart rate variability in
Several cross-sectional and longitudinal studies have
tested whether blood pressure and hypertension would
serve as a mediating risk factor. The findings of cross-
sectional studies have yielded mixed results, which is
not very surprising considering the known problems in
shift work research. Follow-up studies suggest that there
may be some increment of risk related to shift work,
but whether this is a true effect remains to be clarified
in future studies. Subclinical atherosclerosis has been
studied in two large cohorts. These studies showing an
increased risk in shift workers did not have follow-up on
atherosclerosis and thus longitudinal studies are needed
to confirm the association. Recently a relatively high
number of shift work studies have focused on MetS
and type II diabetes, and the current data suggests that
shift work is a probable risk factor for both. Although a
number of longitudinal studies have been published, it
still is premature to make firm conclusions and future
studies should use established definitions of conditions
to ensure better comparability between studies.
Concluding remarks and need for further research
This narrative review has examined the psychosocial,
behavioral, and physiological mechanisms by which
shift work could be a risk factor for CVD and concludes
that there is sufficient evidence for possible disease
pathways – although strong evidence on any specific
plausible mechanism is so far missing. These pathways
are interrelated and may lead to other cardiovascular and
metabolic diseases by increasing the risk for atheroscle-
rosis, metabolic syndrome, and type II diabetes.
In general, there are numerous methodological chal-
lenges in studying the possible mechanisms of the shift
work–CVD relationship. First, there are aspects related
to shift work, such as how to define it? Which shift
characteristics or ways to organize working hours are
essential to health effects, and how can exposure to these
be reliably measured? Second, there are problems in the
assessment of the possible effects of selection (“healthy
worker effect”): are those starting shift work and espe-
cially those staying in it for longer times healthier and/or
do they have a higher tolerance for factors affecting
health? It would also be important to have information
on workers who change the working time model during
follow-up. �ood shift work research faces new chal-
lenges resulting from the transition from traditional,
lifelong, shift work jobs (mainly related to industrial
processes) to flexible, often temporary employment
that has grown increasingly during the last decades. In
such settings, it is difficult to maintain control over large
populations for sufficiently long periods of follow-up to
gain accurate exposure data (ie, years of shift work).
Changes in shift systems may thus modify the con-
clusions on the relevance of different CVD mechanisms.
In a systematic review, Driscoll et al (127) found support
for the use of forward-rotating shift systems for physi-
ological functions. Changing the backward-rotating shift
system to rapidly forward-rotating has been shown to
have a favorable effect on blood pressure (128), sug-
gesting that certain features of the shift systems can
be critical regarding their health effects. Similarly,
increased ergonomic scheduling with a more regular and
predictable shift schedule was found to be associated
with favorable changes in triglyceride and high-density
lipoprotein cholesterol levels (129).
As concluded by Frost et al (3), there is still limited
evidence for a causal relationship between shift work
and ischemic heart disease. To demonstrate causality,
we also need studies on mechanisms. We need more
prospective studies with large representative popula-
tions, good descriptions of the working hours used, long
follow-ups, and reliable measurements of the psychoso-
cial and behavioral stress factors and health outcomes,
as well the use of new physiological biomarkers. In an
ideal study setting, the participant would be recruited to
the study before entering irregular work. This is seldom
possible, but research could focus on the “natural inter-
vention” and study the physiological and behavioral
effects of entering and leaving irregular work. The role
of shift work sleep disturbance in the pathway from shift
work to CVD should be investigated. In order to evalu-
ate the role and extent of sleep disturbance, objective
measures of sleep in addition to the objective measures
of other biomarkers of shift work are needed.
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Received for publication: 5 November 2009