CONTEMPORARY REVIEW

Association Between Work-Related Stress and Coronary Heart

Disease: A Review of Prospective Studies Through the Job Strain,
Effort-Reward Balance, and Organizational Justice Models
Jaskanwal D. Sara, MBChB; Megha Prasad, MD; Mackram F. Eleid, MD; Ming Zhang, MD; R. Jay Widmer, MD, PhD; Amir Lerman, MD

W ork-related stress is an example of a psychosocial risk

factor that has become of interest in today’s ever-
demanding, fast-paced, and globalized society, although its
cornerstone of successful management, and can be achieved
using multivariable risk-prediction algorithms,6–9 of which the
most widely used in clinical practice are the Framingham-
link to adverse health and in particular coronary heart disease based models. These scores assign weights to different levels
(CHD) is incompletely understood. In this review, we will of traditional risk factors, such as age, total cholesterol, and
outline the need to identify novel risk factors for cardiovas- systolic blood pressure, which are combined to generate an
cular disease (CVD) and the potential role of psychosocial risk absolute probability of developing CHD within a specified time
factors, such as work stress; describe the theoretical frame. Framingham-based risk prediction models are well
frameworks by which work stress may influence health; established, practical, and easy to use, supported by large
review evidence provided by observational studies for the link amounts of data and in most cohorts discriminate risk well,
between work stress and CHD; and explore potential mech- after calibration, where necessary.10 Nevertheless, Framing-
anisms that may play a role in this relationship and evaluate ham-based scores are limited by incorporating a limited
the evidence for potential therapeutic interventions in this number of risk factors, such as age, hypertension, diabetes
area. mellitus, dyslipidemia, and smoking, which have been iden-
tified from historically based population studies.11 Alternative
tools to assist in risk prevention have been developed,
The Need to Identify Novel Risk Factors for including the American Heart Association’s Life’s Simple 7,
CVD which identifies a construct of ideal cardiovascular health
characterized by ideal health behaviors: nonsmoking, body
CVDs are the leading cause of death in both men and women
mass index (BMI) <25 kg/m2, physical activity at goal levels,
of every major ethnic group in the United States, of which
pursuit of a diet consistent with current guideline recommen-
CHD is the most prevalent.1 In 2014, >600 000 Americans
dations, and ideal health factors (untreated total cholesterol
were estimated to have a new coronary event and 300 000
<200 mg/dL, untreated blood pressure <120/<80 mm Hg,
had a recurrent event.2 Between 2013 and 2030, medical
and fasting blood glucose <100 mg/dL).12 Although these
costs of CHD are projected to increase by 100%,3
individual concepts are well supported in the literature, the
highlighting a growing health and socioeconomic problem.
Life’s Simple 7 focuses exclusively on “conventional cardio-
Nevertheless, CHD may be preventable,4 and preventative
vascular risk factors,” which in themselves account for
strategies are cost-effective.5 Identification of at-risk groups
between 58% and 72% of all incident cases of CHD.13
and appropriately addressing risk factors form the
Alternative nonconventional risk factors may account for
some of this gap and are becoming increasingly important,
particularly as the effects of previously implemented attempts
From the Division of Cardiovascular Diseases, Mayo College of Medicine, at managing conventional risk factors are being seen. For
Rochester, MN.
example, a recent time trend analysis showed that patients
Correspondence to: Jaskanwal D. Sara, MBChB, Division of Cardiovascular
Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail:
presenting to the catheterization laboratory with CHD had
[email protected] better blood pressure and lipid profiles between 2006 and
J Am Heart Assoc. 2018;7:e008073. DOI: 10.1161/JAHA.117.008073. 2010, compared with between 1994 and 1999,14 which may
ª 2018 The Authors. Published on behalf of the American Heart Association, reflect improved uptake of primary and secondary preventa-
Inc., by Wiley. This is an open access article under the terms of the Creative tive strategies, such as smoking cessation.15 There was also a
Commons Attribution-NonCommercial License, which permits use, distribu-
tion and reproduction in any medium, provided the original work is properly higher proportion of patients taking risk-modifying cardiovas-
cited and is not used for commercial purposes. cular medication.16 Furthermore, in one study of young adults

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hospitalized with their first myocardial infarction, <25% would decision authority, skill discretion, and learning opportunities
have qualified for lipid-lowering therapy based on guidelines is associated with high job strain27 and, in turn, high work
available at the time,17 further demonstrating the limitation of stress. Several studies that have demonstrated an association
current risk-based algorithms. Thus, there is a need to identify between high job strain and an increased risk of CVD have
and account for novel risk factors not currently accounted for shown that both high demands and low control are required to
in traditional risk prevention models. The increasing aware- convey increased risk,27–29 whereas others have shown that
ness of social and psychological determinants of health18 has low job control was more important than high job demand and
opened up novel avenues in which the contribution of these is itself an independent predictor of CVD risk.30–32 There
risk factors to the cause, development, and outcome of remains much controversy in the literature as to whether the
CHD19–21 is becoming increasingly understood. relationship between job demand and control is additive or
One review concluded “there is strong and consistent multiplicative, or if there is a buffering effect. In the latter,
evidence of an independent causal association between once levels of job control reach or exceed a certain threshold,
depression, social isolation and lack of quality social support the deleterious effects of demands are supposedly negated,
and the causes and prognosis of CHD” and that the although to date the precise relationship has not yet been
“increased risk contributed by these psychosocial factors is clarified.33–35 Furthermore, a third component of the job
of similar order to more conventional CHD risk factors such as strain model has been suggested (namely, social support in
smoking, dyslipidemia and hypertension.”22 Similarly, in their the workplace),36 which evaluates the contribution of support
review of the literature, Krantz and McCeney found compelling provided by one’s colleagues and supervisors in the work-
evidence to suggest an association between acute and place. Once again, the buffer theory postulates that social
chronic stress, depression, social support, and socioeconomic support above a certain threshold level protects against the
status with the development of CHD,23 which was in keeping adverse effects of high job strain.34,37
with the findings of Strike and Steptoe in their review of The effort-reward imbalance model (Figure 1) centers on
epidemiologic data.24 the idea that the balance between one’s perceived or actual
Evidence linking work stress and the development of CHD effort into a particular job with one’s actual or perceived
remains unclear however. Of the workforce, 10% to 40% rewards in terms of salary, recognition, and opportunities for
struggle with work-related stress, and at least one third of career progression will influence one’s risks for adverse
these experience severe chronic psychosocial stress.25 In one health outcomes.38,39 Although studies have shown an
national study performed in France, up to 2% of a working association between job strain and CVD mortality,40 evidence
population were affected by illnesses attributable to work- linking job effort-reward imbalance to CVD mortality has been
related stress, which cost society up to 1975 million Euros.26 more sparse. Furthermore, studies that have been able to
It is, therefore, important to examine this potential associa- show an association have typically shown that, of the 2
tion in greater depth, particularly because work-related stress constituent parts, low reward is the more important predictor
is potentially modifiable. of events.31 Another component of this model, personality
traits, such as overcommitment, are seldom evaluated in work
stress related studies, nor is their precise role, interactive or
Theoretical Frameworks Linking Work Stress otherwise, clearly defined in the literature.41
to CHD Further research into work stress has led to the develop-
Evaluating “work stress” as a potential risk factor for CHD is ment of a third framework, known as the organizational justice
challenging, given its subjectivity and the difficulty associated model42 (Figure 1). This model operates under the precept
with synthesizing its significant components into comparable that justice is a fundamental value to the organization of
metrics. Social scientists have tackled this issue by con- society and to individual social interactions,43 and enduring
structing simplified frameworks by which a seemingly abstract perceived unfairness within the workplace can contribute to
concept, such as work stress, can be appreciated in an work stress.44 The model consists of 3 separate entities:
objective way. Investigators have since adopted these frame- distributive justice, which refers to the fairness associated
works in their studies and in doing so have been able to with decision outcomes and the distribution of resources that
generate useful comparisons that help determine the role may be tangible, such as pay, or intangible, such as praise;
work stress plays in CHD. In one of these frameworks, work procedural justice, which is linked to distributive justice in
stress can be characterized from the perspective of “job that it relates to the fairness of the processes that lead to
strain,” as per the job strain model, also known as the outcomes, such that when individuals believe they have a
demand-control model27,28 (Figure 1). This states that work voice in the process or that these processes are consistent,
associated with high psychological demands, such as intense accurate, and without bias, procedural justice is enhanced;
and time-critical tasks, and low control in areas such as and interactional justice, which, in turn, is linked to procedural

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Organizational Justice

Distributive Justice Procedural Justice Interactional Justice

Fairness of Decision Fairness of Decision Making Fairness of Treatment in
Outcomes Processes Communication Processes

Job Strain Effort Reward Imbalance

Job Demands
Rewards
Low High - Salary
Effort
- Esteem
- Demands
- Security
Decision Latitude

Low Job Mediating Factors - Obligation

High

Active - Promotion
Strain

- High Cholesterol
- Hypertension
Low

High Job - ↑ Body Mass Index

Passive
Strain - Maladaptive Behaviors

Coronary
Heart Disease

Figure 1. Outline of the “Job Strain,” “Effort-Reward Imbalance,” and “Organizational Justice” psychosocial models underlying the potential
relationship between work-related stress and coronary heart disease. Individuals with high job strain, effort-reward imbalance, or organizational
injustice may be at an increased risk of coronary heart disease directly or through mediating factors, such as hypertension, high cholesterol, or
maladaptive behaviors.

justice and relates to informational justice, which focuses on as important or potentially even more so than that of the 3
explanations provided to people as to why certain procedures models evaluated.
were used, and interpersonal justice, which reflects the
degree to which people are treated with politeness, dignity,
and respect by those performing procedures. The organiza- Work Stress and CHD
tional justice model was developed later, and it is, therefore, We searched PubMed for potentially relevant articles pub-
less well established than the job strain and effort-reward lished from January 1, 1970, through December 31, 2017,
imbalance models; it has been examined in fewer studies. using the following key search terms: work stress, occupa-
Although these models integrate and combine multiple tional stress, job stress, coronary artery disease, ischemic
different facets of working life, they remain limited in that heart disease, and CVD. Searches were enhanced by scanning
they cannot account for all possible psychosocial and bibliographies of identified articles, and relevant articles were
biological factors that may coexist and contribute to work selected for review. Studies included for selection in this
stress and its relationship with CHD and adverse health in review required the following criteria: characterization of work
general. The precise interplay of extraneous psychosocial and stress using at least 1 of the 3 aforementioned established
biological factors with work stress and CHD is challenging to and validated work-stress models (namely, the job strain,
encapsulate in the form of descriptive models, which are effort-reward imbalance, and organizational justice models);
designed to help simplify seemingly abstract and potentially defined outcomes of incident CHD/ischemic heart disease,
subjective concepts into understandable and comparable characterized by angina or myocardial infarction, or of
constructs. Further investigation is required to better delin- mortality related to CHD; provided a quantitative estimate
eate these relationships. This review focuses on the 3 and confidence interval (CI) of relative risk for incident CHD or
aforementioned models of work stress and does not evaluate CHD mortality and used a prospective causative cohort study
the individual role of other work-related factors, such as design, because randomized controlled trials are not practical
working shift patterns, whose relationship with CHD may be for this study question and prospective cohort studies

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represent the next best level of evidence and can allow combining data from different populations as part of a meta-
inference of causality. Cross-sectional and case-control analysis can become challenging. This is highlighted in a
studies were excluded, as were studies that evaluated the review by Szerencsi et al, in which the authors showed that
impact of multiple individual isolated facets of the work studies undertaken in the United States yielded  26% lower
environment, such as emotional demands, role clarity, career estimates compared with studies conducted in Scandinavian
possibilities, and working overtime. Although they relate to countries when determining the relative risk of CVD using the
adverse psychosocial elements of the working environment, job strain model.54
and some have been shown to be associated with an Figure 2 highlights the countries from which the 23
increased risk of CHD,45 they do not encapsulate work-related prospective cohort studies31,39,40,55–74 that satisfied our
stress per se as a wider construct in the same ways that the 3 inclusion criteria were performed and summarizes the
models selected for this review do. Indeed, work stress can be estimate of risk (relative risk and CI) for incident CHD/CVD
linked to a wide variety of psychosocial risk factors, some of death associated with work stress in each study. Where
which may coexist with work stress, but may not necessarily studies provided a multivariable adjusted estimate of risk, this
correlate with work-related stress incurred on a day-to-day was preferentially included over an unadjusted estimate. All
basis, or form an acceptable measurable synthesis of its studies identified were undertaken in industrialized econom-
relevant constituent parts. Working long hours, for example, ically developed nations from North America, Western Europe,
has been shown to be associated with CHD,46 but individuals Scandinavia, and Japan. These nations would likely lend
working long hours, or shift work, may not necessarily have themselves to broad similarities in the types of jobs their
work stress. Similarly, the authors of the job strain model populations do and have democratic political systems that
stated that “cardiovascular risk results not from a single would likely result in greater oversight and regulation of
factor, but from the joint effects of the psychological working environments and individual worker rights. As such,
demands of the work situation and the range of decision- the results generated by these studies are likely to represent
making freedom with respect to task organization and skill select populations in which working life is relatively more
usage,”27 suggesting an understanding that work stress homogeneous compared with that found in nations with
cannot be usefully characterized by focusing on individual developing economies and alternative political systems. Thus,
work- related factors. The purpose of the current review was the results obtained from the studies included in this review
to examine the relationship between work stress in of itself, may not necessarily be generalizable to workers in other
as a broad construct, synthesizing multiple relevant, yet nations, highlighting the need for further studies to be
unique, aspects of working life and CHD and not to investigate performed in different regions of the world. In addition, the
all individual psychosocial elements related to the working lack of studies performed in developing nations with emerging
environment. economies and distinct social and cultural norms skews our
Often, separate articles were identified that presented data understanding of work stress and its implications on CHD and
from the same study cohort (eg, with different periods of adverse health. Studies performed in developing nations
follow-up or event rates). In these cases, unless the indepen- would enrich our understanding of this question and may
dent or dependent variables were significantly different, only allow the development of newer frameworks that factor in
the study presenting the most comprehensive data was other aspects of working life and society not included in
included. Articles containing no original data, including established models. Furthermore, studies from developing
reviews and meta-analyses, were also excluded to avoid nations may uncover unique methods that local populations
redundancy, particularly because those identified47–52 use to help mitigate work stress that could, in turn, help in the
included cohort studies that were individually selected for development of novel interventions that may be useful in
this review. A further issue with meta-analyses for work stress managing work stress and its adverse health consequences.
is that concepts, such as job strain, effort-reward imbalance, Among the 23 studies identified, 17 evaluated work stress
and organizational injustice, are typically characterized in a through the “job strain” framework only, 2 made use of the
median or quartile split across the population investigated. As “effort-reward imbalance” framework only, 2 evaluated both
Burr et al outlined in their Letter to the Editor, whether certain models separately, and 2 evaluated the organizational injus-
individuals are identified as having job strain, and therefore tice model. Fourteen studies evaluated incident CHD or
have work stress, depends on who else is in the sample.53 ischemic heart disease as their primary outcome, whereas the
This is problematic when work demand, control, and other remaining 9 evaluated the incidence of CVD events or death.
work environment related characteristics vary between jobs Eleven studies found no significant association between work
and across countries. If the prevalence of job strain varies stress and incident CHD/CVD. Among the 12 that did find an
between populations and is inherently dependent on the association, the relative risk (95% CI) for the association
distribution of demands and control within that population, between work stress and incident CHD varied between 1.22

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Figure 2. Illustration of the global distribution of prospective cohort studies evaluating the potential association between work-related stress
and coronary heart disease (CHD) or cardiovascular disease (CVD) mortality. Twenty-three prospective cohort studies were identified up until
December 2017. Studies that provided a quantitative estimate of the association between work stress and incident CHD or CVD events/
mortality and characterized work stress using the job strain, effort-reward imbalance, or organizational injustice model were included. CI
indicates confidence interval; IHD, ischemic heart disease; JACE, Job Stress, Absenteeism and Coronary Heart Disease In Europe study; MONICA,
Multinational Monitoring of Trends and Determinants in Cardiovascular Disease; NHANES, National Health and Nutrition Examination Survey;
and RR, relative risk.

(1.01–1.46) and 4.53 (1.43–14.3), whereas that for the exposures and outcomes. Several of these studies used CVD
association between work stress and CVD events and death as the outcome of interest, which includes non–CHD-related
varied between 1.53 (1.08–1.97) and 1.92 (1.15–3.21). Both pathological conditions, such as cerebral vascular disease,
studies evaluating the organizational justice model found a which makes direct comparisons between studies difficult.
significant association between work stress and incident CHD Along the same lines, studies that evaluated CVD or CHD
or CVD death, as did all 4 studies using the effort-reward events and death look at “hard” outcomes that are easier to
balance model, whereas of the 19 studies using the job strain define accurately than more subjective definitions of CHD,
model, 8 found a positive relationship. Thus, almost as many such as a history of new-onset chest pain consistent with
studies found an association between work stress and CHD as angina, with the former definition likely to generate more
those that did not, and although one study demonstrated a conservative estimates of risk. Using different outcome
>4-fold increase in risk of incident CHD in patients experi- variables defined in different ways raises difficulties when
encing work stress, the great variability in the results from the trying to compare and/or combine results from individual
studies reflects differences in study design, number of studies. Furthermore, the absence of randomization of the
patients included, follow-up duration, and definitions of the exposure variable in all the studies leads to problems with

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confounding and makes it difficult to derive a causal this study included a relatively large sample size (it was
relationship between work stress and CHD with certainty. In overall the sixth largest study included in this review; the
addition, the studies included in this review represent a largest study included 35 471 subjects, whereas 6 studies
relatively homogeneous group and share many similarities in included <1000 subjects) and used a prospective design, one
study design, in part because they are all prospective of its major limitations relates to the generalizability of the
causative studies, but also because the nature of this results. The British civil servants included in this study
particular study question is limited in the number of study comprise “white collar” workers and are not comparable to
designs it can lend itself to. Important differences in sample manual laborers working in “blue collar” jobs. Moreover, the
size, demography, length of follow-up, and which exposure outcomes used in this study were subjectively determined by
and outcome variables were used are highlighted in Figure 2. each employee and may correlate poorly to actual CHD, a
Herein, we outline some additional key issues related to study problem encountered in other studies using a survey-based
design that we believe are best illustrated through critiquing approach to quantify outcomes. Studies relying on objective
the 2 studies by Kuper et al61 and Kivimaki et al,31 which determinants of the outcome variable, such as myocardial
both included an assessment of the job strain and effort- infarction, identified from clinical records may arrive at more
reward imbalance model, and are therefore more accurate conclusions, particularly because subjects who
comprehensive studies that collectively highlight important report experiencing job strain may have an inherent disposi-
methodological considerations common to all studies tion making them more likely to report physical symptoms,
included in this review. such as chest pain/tightness, that may have organic causes
The Whitehall Study was one of the earlier cohorts to be but could also represent a psychosomatic process. All studies
evaluated for the relationship between work stress and CHD, included in Figure 2 also made use of written surveys and/or
and in one study, Kuper et al examined this association direct in-person interviews with employees and sometimes
among 10 308 (67% men, aged 35–55 years) civil servants in managers as well when characterizing work stress as the
London, England.61 This study followed a prospective cohort exposure variable. This poses another problem because not
design in which subjects completed questionnaires at base- only does this method involve a subjective component that
line (1985–1988) and on 2 subsequent follow-up visits may be influenced by the interpretation of each question and
(1989–1990 and 1991–1993) consisting of questions asking the interviewing style of the questioner, among other factors,
about job control, job demand, and social support at work. In but there is also a possibility of responder bias. Those
addition, questions derived from the previously validated Rose subjects who choose to participate in studies by responding
Questionnaire75 were used to assess for new angina or severe to surveys, taking part in interviews, and then engaging with
pain across the chest, a new diagnosis of ischemic heart follow-up are likely to be systematically different to those who
disease, or any coronary event. The subjects’ managers also do not respond or follow up, who may in general be less
completed a questionnaire at baseline, providing an indepen- health conscious or too “stressed” at work to find time to
dent assessment of employee job strain. The investigators participate in studies. A unique quality of this study was that
demonstrated that men and women with low job control had a the investigators evaluated the cumulative effect of job stress
higher risk for newly reported CHD at follow-up compared with an independent assessment of the impact that work
with those with high control and that the odds ratio (95% CI) stress had on CHD at multiple follow-up points. There was
between men and women did not vary significantly (1.55 also an independent assessment of job strain provided by
[1.20–2.01] versus 1.74 [1.15–2.64]). Furthermore, the questionnaires answered by managers as well as a subjective
investigators found that low job control had a cumulative assessment of job strain completed by employees. Although
effect on newly reported CHD rates, with subjects with low these correlated poorly with each other (correlation coeffi-
control on both follow-up occasions having the highest odds cient, 0.41), both measures were associated with newly
of new CHD (odds ratio, 1.93 [95% CI, 1.34–2.77]). This reported CHD, demonstrating that objective measures of work
association could not be explained away by employment strain may be as important as those reported by the individual
grade or conventional CVD risk factors. A dose-response workers.
relationship between job strain and the relative risk for acute Other problems related to the studies included in Figure 2
myocardial infarction has been demonstrated in other relate to the fact that previous studies have shown that
studies.31,76 Last, there was no significant association psychosocial stressors have a tendency to coexist and cluster
between job demand and social support in the work such that individuals from lower socioeconomic status
environment with newly reported CHD. backgrounds tend to also have poorer social support and
The previously described study highlights some of the education levels as well as a higher prevalence of conven-
design characteristics and methodological issues commonly tional CVD risk factors and certain “maladaptive” psycholog-
encountered by other studies included in Figure 2. Although ical traits24 compared with their counterparts from higher

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socioeconomic status backgrounds. Thus, when one social and high effort-reward imbalance had a relative risk (95% CI)
factor, such as higher socioeconomic status, is shown to be of 2.20 (1.16–4.17) and 2.36 (1.26–4.42) for CVD mortality,
associated with lower rates of CHD,77 it can be challenging to compared with those with low job strain and low effort-reward
determine if any coexisting variable is, in fact, playing a role, imbalance, respectively. These ratios remained significant
and if so, to what extent. Randomization is a useful technique after adjusting for occupational grade and behavioral risk
in experimental studies that can balance covariates between factors, including negative affectivity, defined as a predispo-
groups exposed and not exposed to the variable of interest, sition to respond to questionnaires negatively, which may
although to date no randomized trial has been published erroneously inflate any observed associations. Low job control
evaluating the relationship between work stress and CHD, predicted CVD mortality before, but not after, adjustment, and
likely because of the practical difficulty of “assigning” a group neither high job demand nor high job effort predicted CVD
to work stress. As such, a significant problem with the studies mortality. This latter finding highlights the previously stated
included in this review is discriminating whether work stress contention put forth by the conceivers of the job strain model
itself is responsible for the identified effect on CHD. Part of that “cardiovascular risk results not from a single factor, but
the increased risk of CHD in individuals from lower socioe- from the joint effects of the psychological demands of the
conomic status backgrounds has been attributed to low work situation,”27 underscoring the fact that work stress, and
control in the workplace.78 In another study that included in turn CHD, cannot be usefully predicted by focusing on its
>2000 Finnish men, those in the lowest socioeconomic status individual factors but rather the sum of its consistent parts.
quintile, determined by income, had an age-adjusted hazard A unique facet of the study by Kivimaki et al31 was the fact
ratio (95% CI) for cardiovascular mortality of 2.66 (1.25–5.66) that blood pressure and serum cholesterol were measured at
compared with those in the highest socioeconomic status follow-up after 5 years and BMI was measured after 10 years.
quintile.79 This reduced to a hazard ratio of 1.71 (95% CI, High job strain was associated with increased serum choles-
0.76–3.86) when depression and psychosocial factors, such terol at 5 years’ follow-up, and high effort-reward imbalance
as social support, were controlled for, suggesting that was associated with increased BMI at 10 years’ follow-up.
clustered psychosocial risk factors incrementally influence These results suggest a potential, and plausible, mechanism
risk of disease and, in their absence, socioeconomic status in for the relationship between work stress and CHD and thus
itself may not be associated with CVD. Adjusting for conventional CVD risk factors, such as high cholesterol and
covariables can be a useful way to unpick these associations. hypertension, could be integrated into a partial mediation
This was illustrated in another study by Johnson et al,59 in model (Figure 1). These findings could also support the
which the authors evaluated the relationship between job incorporation of work-stress models into conventional CHD
strain and CVD death and controlled for confounding biolog- risk prediction algorithms by linking work-related stress with
ical variables, such as known CVD risk factors, and psy- our knowledge about biological risk factors and their
chosocial risk factors, such as social isolation, and were still associations with inflammation80,81 and endothelial
able to demonstrate a significant association. Although dysfunction82–85 that form the pathological basis of CHD.
adjusting for covariates can seem helpful in proving or In addition to the study by Kivimaki et al,31 others have
disproving an independent risk factor–disease association, it also shown an association between effort-reward imbalance
can mask the true role of some factors that may, in fact, have and the incidence of CHD,38,56,78 but compared with studies
mediating roles or act synergistically with other factors, the evaluating job strain, these remain few. A potential explana-
studying of which may provide greater insight into the precise tion for this is that the job strain model has been longer
mechanisms underpinning the relationship between work established, is given more weight, and is thus investigated
stress and CHD. more frequently. Also, high job effort and high job demand,
In our second study, Kivimaki et al31 examined the impact each of which individually contribute to the synthesis of work
of work stress on CHD among 812 (67% men) Finnish stress in their respective models, may be viewed as similar
industrial employees, including managers, other office staff, constructs, and indeed in the study by Kivimaki et al,31 some
skilled workers, and semiskilled workers, all of whom were of the questions relating to job effort were identical to those
free of CVD at baseline. A major strength of this study was the relating to job demand. Some investigators may, therefore,
inclusion of a wide diversity of occupational groups enhancing not perceive these 2 work models to be distinct and would not
the generalizability of the findings, unlike the Whitehall study, want to reduce the sensitivity of detecting an effect between
which included a homogeneous group of “white collar” civil work stress and CHD by duplicating or reusing potential
servants. The outcome assessed was CVD mortality anytime survey questions in an attempt to capture a measure of both
between 1973 and 2001, and it was determined from Finnish models. Instead, they may choose to only study one model
National Mortality Registries. The authors found that, after and choose the more well-established and frequently studied
adjustment for age and sex, employees with high job strain job strain model. Only 2 studies included in Figure 2

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evaluated the organizational injustice model, one of which the female population and may also contribute to how work
was based from the Whitehall Cohort.74 This study also used stress may be a less important psychosocial risk factor
surveys to characterize organizational injustice and used among women. There is also some evidence suggesting that
medical records to identify new definite angina and myocar- there are sex-based differences in the experiences of stress
dial infarction as well as CHD death. The study showed a that could lead to differences in the response to surveys.87
significant association with level of justice at work and
incident CHD, even after adjusting for conventional CVD risk
factors. Similarly, significant results were obtained in the Potential Mechanisms for a Link Between
study of Elovainio et al,72 which also evaluated justice at Work Stress and CHD
work, this time using a national mortality register to identify There are several mechanisms by which it is plausible that
cases of CVD death, suggesting that the organizational work stress can contribute to the development of CHD
injustice model, as an independent index of work stress, may (Figure 3). Biological pathways implicated in the development
also be used to predict CHD. of CHD may be influenced by psychosocial factors. Under
Of the 23 studies included in this review, 11 evaluated normal physiological conditions, cortisol secretion is
samples consisting of 100% men, whereas 1 study evaluated increased in response to psychological stress and elevated
90% men and a further 4 studies evaluated 67% men. Among levels have been documented in states of depression and
these 16 studies, 11 found a significant association between hostility as well as work stress.20,88,89 Although cortisol
work stress and CHD, whereas among the 11 studies normally reduces inflammation, oversecretion may result in
consisting of 100% men, 7 showed a significant relationship. resistance to its anti-inflammatory properties, rendering the
The strongest relationship was demonstrated in the study by body vulnerable to inflammatory disorders, such as
Siegrist et al, in which effort-reward imbalance was associ- atherosclerosis.80,81 For example, high job demand has
ated with a relative risk of 4.53 (95% CI, 1.43–14.3) for been associated with more rapid progression of carotid
incident CHD,39 although this was one of the smaller studies atherosclerosis.90 Excessive cortisol may also result in
included in this review, with 416 participants. Although there dysregulation to the negative feedback system of the
are studies that fail to show a significant relationship between hypothalamic-pituitary-adrenal axis, further perpetuating ele-
work stress and CHD, overall there seems to be a trend vations in cortisol. Increased inflammatory markers, such as
favoring an association and the strength of this relationship C-reactive protein and interleukin-6, have prospectively pre-
appears to be in the region of an increased risk of 30% to 50%, dicted coronary events in healthy asymptomatic populations,
although there is some variability. Among the 3 studies and elevated levels of C-reactive protein and other proinflam-
including 100% women, only 1 demonstrated a significant matory cytokines have been noted in individuals with
relationship between work stress and CHD, with job strain depression.91 This, however, has not been demonstrated in
being associated with a relative risk of 1.63 (95% CI, 1.28– subjects with high work stress. It may be that elevated
2.08) for CVD events,66 which also included stroke. The 2 inflammatory cytokines, such as tumor necrosis factor-a,
studies that did not show a relationship between work stress noted in depression, are responsible for this condition’s
and CHD were the 2 largest studies included in this review, physical symptoms of anorexia and sleep disturbance in the
both of which had sample sizes >35 000 and focused same way as for malignant diseases but may not have a direct
specifically on incident CHD, as opposed to non-CHD CVD role in linking psychosocial stressors to CHD.
outcomes as well. Thus, the link between work stress and Work stress has also been associated with increased levels
CHD among women has not been consistently demonstrated, of epinephrine and long-term sympathetic activation,20 which
although there is likely insufficient evidence in this area and may have a role in activating platelets and macrophages,
further studies evaluating the relationship between work upregulating the expression of inflammatory cytokines,92 and,
stress and CHD in women are required. The discordance in as with cortisol, contributing to the development of high blood
results between men and women may be related to the fact pressure, glucose intolerance, and dyslipidemia, all compo-
that CVD affects women later in life, possibly even after they nents of the metabolic syndrome. In fact, work stress
have completed their “working lives.” Also, Orth-Gomer et al has been shown to be an independent risk factor for
demonstrated that psychosocial risk factor burden and hypertension,93,94 and job strain, in particular, results in
resources at home may have a stronger contribution to higher ambulatory blood pressure levels in a dose-response
health in women compared with men,86 and as such work relationship, even beyond working hours.94 Although hyper-
stress may have a comparatively lesser role in determining tension is a conventional cardiovascular risk factor associated
health outcomes in women. There was also sparse informa- with increased rates of CHD, cardiovascular reactivity is a
tion provided on the engagement in part-time work in the novel risk factor that may promote atherogenesis and lead to
studies included in this review, which may be more frequent in CVD events. In one study, greater cardiovascular reactivity

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Work Stress and Coronary Heart Disease Sara et al

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Mechanisms Underlying the Relationship between Work Stress and
Coronary Heart Disease

COAGULATION INFLAMMATION MALADAPATIVE AUTONOMIC ENDOCRINOLOGIC

BEHAVIOURS NERVOUS SYSTEM

Thrombophilia Pro-Inflammatory Smoking ↑ Cardiovascular Hypothalamic-

Cytokines Reactivity pituitary-adrenal
Impaired Alcohol Excess axis dysregulation
Fibrinolysis Upregulation of Hypersecretion of
Inflammatory Binge Eating Epinephrine Hypercortisolism
↑ Concentration Cells
of Clotting Physical
Factors Inactivity

Obesity Glucose
Intolerance

Hypertension

Endothelial Dysfunction
and Atherosclerosis

Figure 3. Potential mechanisms by which work-related stress may lead to coronary heart disease.

was demonstrated in subjects with work stress.95 Similarly, younger men.100 In another study among Korean blue collar
low socioeconomic status and mental stress have both been workers, who worked in jobs such as shipbuilding and
linked to pathological lipid profiles.96,97 Although one study manufacturing industry, effort-reward imbalance was associ-
suggested that work stress does not influence serum lipid or ated with metabolic syndrome, characterized as the presence
glucose levels,98 several other studies have shown a link of all 5 components of the syndrome, in both men and
between components of the metabolic syndrome and work women.101 Although these studies are limited by their cross-
stress. For example, in one French cross-sectional study sectional design, several prospective studies have shown
consisting of 43 593 men and women, work stress, charac- similar findings. In one study that followed up 290 police
terized by the effort-reward imbalance model, was associated officers over a 5-year period, work stress, characterized as job
with significantly lower levels of high-density lipoprotein strain or effort-reward imbalance, was associated with
cholesterol among men and a higher BMI in both men and metabolic syndrome as well as hypertriglyceridemia, even
women, even after adjusting for covariables, such as age, after adjusting for numerous sociodemographic variables
socioeconomic status, health-related behaviors, and symp- (namely, age, rank, education, geographic origin, marital
toms of depression.99 In another study from Germany, work status, housing, presence of offspring, smoking, and sleep
stress, also characterized by the effort-reward imbalance habits). The authors also found that job demand and work
model, was associated with the metabolic syndrome, which effort were independent predictors of metabolic syndrome.102
was defined as the presence of at least 3 of the following 5 In a further prospective study that included an unselected
components: increased blood pressure, elevated triglycerides, population-based cohort, job strain as well as low-decision
low high-density lipoprotein, increased fasting glucose, and latitude in isolation were significantly associated with new-
central obesity. This relationship was strongest among onset type 2 diabetes mellitus among women. Interestingly,

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Work Stress and Coronary Heart Disease Sara et al

CONTEMPORARY REVIEW
high job strain and high work demand in isolation decreased physical activity on the job, interpersonal stress, job control,
the risk of new-onset type 2 diabetes mellitus among men. and job demands were not significantly associated with
Further studies will be required to better understand the carotid intima-media thickness at baseline or with its
relationship between work stress and the various components progression over time. Among men, the only significant
of metabolic syndrome as well as the potential effect predictor of increased carotid intima-media thickness over
modification of sex. time was occupational position, such that those in roles such
The stress associated with increased workload is associ- as farming, fishing, construction, extraction, and transporta-
ated with increased platelet count and aggregation as well as tion had more significant disease progression compared with
elevated levels of factors VII and VIII,103 resulting in a those in professional roles. Among women, the only predictor
prothrombotic state. In addition, work stress has been shown of carotid intima-media thickness progression was physical
to lead to impaired fibrinolysis through decreased levels of hazards on the job.118 Further study of this and other novel
tissue plasminogen activator and increased levels of plas- risk factors for CVD would be useful. The aforementioned
minogen activator inhibitor antigen.104 The relationship description of potential biological mechanisms that may
between work stress and fibrinogen levels, however, remains underlie the relationship between work stress and CHD
more uncertain. Although several large studies have found represents a simplified view that does not factor in the
that increased levels of work stress are associated with potential roles of other occupational and social factors that
elevated fibrinogen levels,105–107 other studies have failed to could contribute to work stress and its effect on CHD. Further
show any association.104,108 One study, in particular, demon- studies are required to clarify the role of these and additional
strated that in the setting of mental stress, subjects with low psychosocial and environmental factors in mediating the
job control had an exaggerated fibrinogen response compared relationship between work stress and CHD and adverse health
with those with high job control.109 Elevated fibrinogen levels in general and to determine what pathophysiological conse-
are a powerful predictor for myocardial infarction110,111 and quences they may have.
are associated with several cardiovascular risk factors,112–114 In addition to intrinsic markers becoming deranged with
thus providing a potential mechanistic explanation for an increased work stress, the work environment can contribute
increased risk of coronary events among those experiencing to the adoption of high-risk behaviors among individuals,
increased work stress. Increased job strain among both men further increasing the risk of CHD. Increased job strain has
and women was associated with elevated levels of fibrinogen, been linked to unhealthy behaviors, such as smoking, physical
which, in turn, were associated with increased age, BMI, and inactivity, and poor diet,119 an association that has also been
total cholesterol as well as the presence of hypertension, noted with other psychosocial stressors, like social isolation,
smoking, and diabetes mellitus.115 and conditions, such as depression. Moreover, workplaces
Endothelial dysfunction is characterized by reduced coro- that focus on healthy living and the overall physical and
nary blood flow secondary to impaired vasoreactivity of the mental wellbeing of their employees are more likely to provide
coronary microcirculation and/or epicardial vessels. It can a favorable work environment, with decreased job strain, in
precede atherosclerosis and may independently lead to part through the promotion of physical exercise and making
adverse CVD events.83 Short-term episodes of mental stress use of gyms and “wellness centers.”120
have been shown to cause reversible endothelial dysfunction
in healthy individuals.85 Although depression has been
associated with endothelial dysfunction,116 the precise role Management of Work Stress
work stress plays on endothelial function remains uncertain. Because work-related stress may contribute to an increased
Given its central role to several potential mechanisms related incidence of CHD, it is important to explore possible
to both work stress and CHD, including inflammation, and interventions that may help alleviate work-related stress.
modifiable cardiovascular risk factors (Figure 3), endothelial van der Klink and colleagues studied the effectiveness of
dysfunction may play a pivotal role in the link between work occupational stress-reducing interventions in a meta-analysis
stress and cardiovascular health and could potentially offer an that included 48 studies (n=3736) and reported that
integrated index of risk. However this remains an understud- individual-directed interventions were more effective than
ied area and requires further investigation. The relationship occupational-based interventions and that, of these, cognitive-
between other novel risk factors for CVD and work stress has behavioral therapy based interventions were most effective
also been sparsely studied, an example of which is carotid (Cohen’s d, 0.68; P<0.05).121 Previous studies have also
intima-media thickness, which, like endothelial dysfunction, is supported this finding.122 Cognitive-behavioral therapy had
a marker of subclinical atherosclerosis and is associated with the most positive effect on outcomes, such as psychologic
an increased risk of CVD events.117 In one prospective study responses and resources to stress and complaints of anxiety-
following up 3109 workers over a period of 9.4 years, related symptoms and had the added benefit of having an

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Work Stress and Coronary Heart Disease Sara et al

CONTEMPORARY REVIEW
inverse relationship between effect size and number of distress, blood pressure, heart rate, and serum cholesterol.
required sessions. Relaxation therapy was the next most Half of the included studies evaluated the impact on morbidity
effective intervention (Cohen’s d, 0.35; P<0.05) and was the and mortality and found that patients not receiving psychoso-
best intervention for modifying psychophysiologic outcomes. cial treatments had higher mortality and adverse cardiac
The authors also concluded that stress-related interventions event rates compared with those receiving these
worked best in employees who have greatest job control at treatments.127 Thus, these interventions were able to posi-
baseline. Conversely, in another systematic review, Lamon- tively influence both biological and psychosocial symptoms
tagne et al evaluated 90 studies assessing work-stress and, in doing so, yielded improvements to patient outcomes.
interventions between 1990 and 2005 and concluded that Subsequent meta-analyses demonstrated mixed results, with
the best interventions were those that included both individ- 1 demonstrating a positive effect of psychosocial treatments
ual and organizational focused interventions, and where only on cardiac morbidity,128 2 demonstrating no effect of these
one was present, organizational interventions were more treatments on cardiac morbidity,129,130 and a final review,
important.123 This may be because the effects of a single which evaluated 14 psychosocial intervention trials, demon-
intervention affect more people but does not take into strating a mixture of positive and equivocal influences of
consideration the cost and time that may be required to psychological treatments on cardiac morbidity.20 These
implement an occupational-based intervention. Although studies further implicate a psychosocial component contribut-
occupational-based interventions tend to enhance an employ- ing to the cause of CHD and suggest that symptoms related to
ee’s level of job control, individualized interventions improve stress may form important targets for psychosocial interven-
perceptions and coping skills.124 The most effective interven- tions. In addition, although many studies fail to show an
tions, therefore, seem to be individualized cognitive-behavior improvement in cardiac events, some have shown improve-
therapy–based interventions in subjects with preexisting high ments in more modest, but nevertheless relevant, end points.
levels of job control, which may be achieved by influencing One study, for example, found psychosocial intervention
perception of work environment and enhancing psychological programs to improve markers of CVD risk, such as endothelial
resources. For those with low job control, occupational dysfunction.131 Further interventional trials evaluating larger
interventions that provide greater variety in daily tasks with sample sizes are necessary to elucidate which treatments are
increased decision-making capacity may enhance job control. most effective and which individual characteristics respond
This can be demonstrated using social cognitive theory, which best to them. Although contemporary primary and secondary
highlights the importance of improved self-efficacy, positive preventative pharmacotherapy and behavioral modifications
reenforcement of newly developed constructive behaviors, have been implemented and yield results on the population
higher levels of self-determinism, and ultimately reciprocal level, psychosocial interventions may require a greater degree
determinism through positive influence on the behavior of of individualization, depending on patient demographics,
oneself, one’s colleagues, and one’s environment.125 Workers psychosocial characteristics, and symptoms.
with enhanced control may then benefit more from cognitive- The vast majority of the interventions to improve work
based therapy interventions, where appropriate. Where stress that have been trialed in the workplace and studied
neither method works, passive strategies to enhance coping have focused on individual-based measures. This overempha-
and address symptoms with relaxation therapy may be sis of individual-based interventions, as opposed to wider
suitable, which could be available to employees in their modifications to the work environment, does not necessarily
workplace. How organizations actually enact some of these mean that individual-based interventions are more effective,
changes is challenging. One systematic review by Narvaez but may reflect the fact that these interventions are easier to
et al outlined the importance and effectiveness of using implement and study. Workplace-based interventions are
measures supported by information technology to help inevitably more costly, take more time to implement, and
prevent and treat work-related stress.126 However, these require the relevant workplace management to commit to the
interventions have been infrequently used to date, and what workplace-based changes. This in itself introduces further
exactly is the role of information technology in the manage- potential bias because management willing to modify work-
ment of work stress remains unclear. place environments to help improve work stress may belong
A meta-analysis looking at 20 randomized controlled trials to a group of managers who acknowledge the importance of
evaluating the utility of several psychosocial treatment workers’ wellness and have already implemented other
strategies, including relaxation training, cognitive-behavioral workplace measures to help mitigate workplace-related
therapy, meditation, group emotional support, and the stress. Management willing to make significant changes to
provision of home nursing interventions, to reduce stress a work environment to combat stress may also have spent
found that patients receiving psychosocial treatments showed time previously in cultivating a workplace culture of lower
greater reductions compared with controls in psychological levels of stress and greater emphasis on employee wellness.

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These systematic differences between managers willing to and CHD. Work stress is likely to remain a significant facet
implement workplace environment changes to help alleviate of the 21st century lifestyle and, with this, further work is
stress and those unwilling or unable to implement changes required to determine its precise role in the pathological
make it difficult to determine if modifying the workplace features of CHD and which interventions can be best used
environment per se is responsible for improvements in work to modify it.
stress and, in turn, CHD and adverse health or if the
preexisting factors were more relevant. Investigating modifi-
cations to the workplace environment on their own as part of Acknowledgments
a randomized controlled trial would be a costly and time- All authors contributed significantly to this article and have read and
consuming undertaking and, as yet, studies of this nature are approved of the final version.
sparse. Furthermore, although individual-based therapies are
easier to implement, are simpler to evaluate as part of a
controlled study, and are likely to be less costly, the Disclosures
effectiveness of individual-based therapy in one individual or None.
group does not necessarily translate into effectiveness in all
individuals or groups. Individuals are different and bring with
them a unique mixture of psychosocial attributes, personality References
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