Annals of Physical and Rehabilitation Medicine 60 (2017) 6–12

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Original article

Stress, anxiety and depression in heart disease patients:

A major challenge for cardiac rehabilitation
Jean-Christophe Chauvet-Gelinier a,b,*, Bernard Bonin a,b
a
Service de Psychiatrie et d’Addictologie, Centre Hospitalier Universitaire, 14, rue Gaffarel, bâtiment Marion, 21000 Dijon, France
b
Laboratoire de Psychopathologie et Psychologie Médicale, EA 4452, IFR Santé STIC 100, Université de Bourgogne-Franche-Comté, France

A R T I C L E I N F O A B S T R A C T

Article history: Cardiovascular events and emotional disorders share a common epidemiology, thus suggesting
Received 18 September 2016 fundamental pathways linking these different diseases. Growing evidence in the literature highlights
Accepted 25 September 2016 the influence of psychological determinants in somatic diseases. A patient’s socio-economic aspects,
personality traits, health behavior and even biological pathways may contribute to the course of
Keywords: cardiovascular disease. Cardiac events often occur suddenly and the episode can be traumatic for people not
Cardiac rehabilitation prepared for such an event. In this review of the literature, the authors tackle the question of
Chronic stress
psychobiological mechanisms of stress, in a pathophysiological approach to fundamental pathways linking
Anxiety disorder
Depression
the brain to the heart. Various psychological, biological and genetic arguments are presented in support of
the hypothesis that various etiological mechanisms may be involved. The authors finally deal with
biological and psychological strategies in a context of cardiovascular disease. Indeed, in this context, cardiac
rehabilitation, with its global approach, seems to be a good time to diagnose emotional disorders like
anxiety and depression, and to help people to cope with stressful events. In this field, cardiac rehabilitation
seems to be a crucial step in order to improve patients’ outcomes, by helping them to understand the
influence of psychobiological risk factors, and to build strategies in order to manage daily stress.
ß 2016 Elsevier Masson SAS. All rights reserved.

1. Introduction – epidemiological features
There is a substantial amount of evidence in the literature
underlining the impact of psychological determinants on the onset
of heart disease. Depression, a disease with a very high
psychosocial burden, also has a detrimental effect in terms of
cardiovascular disease. Indeed, people suffering from depression
are as twice as likely as the general population to develop
myocardial infarction [1] and this cardiovascular comorbidity
increases mortality in people with depression, even more than
death by suicide [2]. Although the precise nature of the links
between depression and coronary heart disease (CHD) have not yet
been clearly established, these links are being highlighted more
and more frequently, first of all from an epidemiological point of
view and then with regard to the etiological and clinical aspects in
patients with this worrying comorbidity. Quite recently, Eichstaedt
et al. showed in a US county a robust positive relationship between
negative emotions (anger, hostility, boredom) expressed in twitter
messages and cardiovascular deaths, thus strengthening the link
between negative thinking and cardio-metabolic disorders [3]. A
few years ago, the Interheart study reported the impact of psychic
disease on coronary artery disease and the importance of
psychosocial stress (a notion that includes depression), which
was put in third place in the league table of risk factors (with an
odds ratio of 2.67) for developing cardiovascular disease [4], after
the apolipoprotein B/apolipoprotein A1 ratio and smoking but in
front of diabetes, arterial hypertension and abdominal obesity.
Negative emotional states therefore appear to be strongly
associated with cardiovascular events. Because of these psycho-
logical, behavioral and biological relationships between the brain
and heart, it seems important to consider the reality of these
deleterious links before including specific strategies in rehabilita-
tion programs in order to reduce adverse consequences in patients
with cardiovascular disease.

* Corresponding author at: Service de Psychiatrie et d’Addictologie, Centre
Hospitalier Universitaire, 14, rue Gaffarel, bâtiment Marion, 21000 Dijon, France.
E-mail address: jean-christophe.chauvet-gelinier@chu-dijon.fr
(J.-C. Chauvet-Gelinier).
2. Methods
In this review, relevant studies from 2000 to 2016 were selected
and analyzed (Fig. 1). Medical subject heading (MeSH) terms

http://dx.doi.org/10.1016/j.rehab.2016.09.002
1877-0657/ß 2016 Elsevier Masson SAS. All rights reserved.
 J.-C. Chauvet-Gelinier, B. Bonin / Annals of Physical and Rehabilitation Medicine 60 (2017) 6–12
‘‘stress’’, ‘‘anxiety’’, ‘‘depression’’, ‘‘personality’’, ‘‘cardiovascular
disease’’ and ‘‘rehabilitation’’ were used to perform key word
searches of the PubMed database.
3. Results
Fig. 1 shows studies and results of the selection and screening
process. In total, 201 papers were founded through PubMed
database searches. After removing duplicates, 145 remained. Of
these, 70 papers were reviewed and 31 were not related to
research designs and were excluded. Thirty-nine studies remained
and 11 articles were excluded because of methodological bias (e.g.
inclusion/exclusion criteria, etc.). Then, 28 studies appeared to be
suitable, in relation to stress, anxiety and depression in people with
heart disease. Studies included showed the cardiovascular impact
of either usual psychological stress or emotional disturbances like
anxiety and depression. In addition, several studies illustrated the
scientific rationale for anxiety/depression diagnosis in people with
heart disease and the dramatical interest of stress management
especially in cardiac rehabilitation.
3.1. The cardiovascular impact of stress in usual conditions
There is more and more evidence of the impact of psychological
factors on the onset of somatic diseases in general and
cardiovascular disease in particular. In the field of psychobiological
theory, which tries to explain the link between the brain, cognition,
emotion and body, stress theory is a credible way to model this
psychosomatic enigma. The stress response appears to play a
Fig. 1. Flow diagram of results of selection process.
7
central role in the interface between the brain, feelings, behavior
and biological effects. The old concept of stress by Hans Selye has
moved forward, because of progress in medical sciences and
psychology. Indeed, as Hans Selye used to say, stress is life, and the
brain and body must constantly adapt in order to respond to
various stimuli [5]. The effect of multiple stimulations makes the
body respond in biological, cognitive and emotional ways. The
stress response involves the central activation of brain systems
responsible for the analysis of the environment. This response is
important and appears not to be deleterious, as it promotes a
physiological balance in response to classic and normal environ-
mental stressors. However, in the case of chronic and mainly
psychosocial stressors, the allostatic system may be overwhelmed
with hyperactivation of the hypothalamic–pituitary–adrenal axis
and the autonomic nervous system with dysregulation of blood
pressure and cortisol levels [6]. In addition, an immuno-
inflammatory response occurs with the production of inflamma-
tory cytokines [7]. If this phenomenon lasts for a long time because
of chronic adversity (work or social stress, for instance), the
pathophysiological effects can lead to metabolic disturbances
(glucose and lipid dysregulation), metabolic syndrome and
cardiovascular disease [8] (Fig. 2). Then, psychological factors like
perceived stress, coping style, personality traits, or social support
might modulate the stress response.
3.1.1. Perceived stress
The reaction to stress is not an automatic process directly
associated with the environment or stressors, but stress occurs in a
transactional way between the environment and the subject
8 J.-C. Chauvet-Gelinier, B. Bonin / Annals of Physical and Rehabilitation Medicine 60 (2017) 6–12
Fig. 2. Simplified schema of neurobiological action of stress, adapted from Marik and Bellomo 2013 [6].
[9]. This is why perceived stress is a better approach to describe
stress reactions. Perceived stress is the subjective evaluation of
stressors, in a non-linear manner from the stressor to the stress
response, depending on personal properties like gender and
experience. What is important to note is that the same traumatic
event may be experienced quite differently by two different people
because of differences in perceived stress. Though the intensity of
the perceived stress may be associated with biological and
psychological consequences, other psychological dimensions, such
as coping strategies or personality traits, are involved in the stress
reaction.
3.1.2. Coping style
Coping is defined as all the cognitive and behavioral efforts
made in order to manage internal or external stimuli potentially
exceeding personal resources. The use of one or another coping
strategy is determined by the stress event (type, severity, length,
controllability, etc.) and by the subject’s profile (cognition,
personality, personal history, etc.) [9]. Two main coping strategies
are described, a problem-focused coping style and an emotion-
focused coping strategy. A problem-focused coping strategy is an
active strategy that relies on using active ways to directly tackle
the situation that caused the stress. Emotion-focused strategies
aim to reduce and manage the intensity of the negative and
distressing emotions that a stressful situation has caused rather
than solving the problematic situation itself. Problem-focused
strategies seem to be more effective in manageable situations like
coronary heart disease where drug observance and balanced diet
are required to improve the disease outcome. However, in
situations of unsolvable situations (diseases with a bleak progno-
sis, for instance), emotion-focused strategies are useful to cope
with the situation, by escaping from the dark reality, etc. In
controllable diseases or in terms of diet or health behavior where
active strategies may be required to avoid dangerous behavior, a
problem-focused style is effective to solve problems and to reduce
the effects of stress.
3.1.3. Personality traits
In the history of the concept of stress and psychosomatics,
personality clusters used to be an important notion. Indeed, in
early reports, the Type A personality, defined by the combination of
several traits encompassing a sense of time urgency, high job
involvement, strong drive, a need for achievement, ambition and
competitiveness, was associated with coronary artery disease.
However, subsequent studies have dismissed this link and focused
on hostility as the ‘‘toxic’’ component [10,11]. Indeed, cardiovas-
cular mortality was found to be primarily due to cognitive hostility
(i.e. hostile thoughts rather than hostile behavior) but not to Type A
personality. In the context of chronic diseases, Type A personality
was even associated with increased survival, especially in coronary
heart disease and in diabetes [12,13]. Indeed, Type A people are
goal-oriented and often adhered to medical advice and treatments,
which may partially explain better outcomes observed in Type A
people suffering from cardiac disease [14,15]. Beside the Type A
 J.-C. Chauvet-Gelinier, B. Bonin / Annals of Physical and Rehabilitation Medicine 60 (2017) 6–12
concept, the Type D personality defined by Johan Denollet as a
personality associating negative affectivity and social inhibition was
linked to CHD [16]. Type D people experience extreme difficulty
going towards other people, in a manner of social phobia, with an
avoiding coping style. It is known that the lack of social support is
associated with cardiovascular disease, probably by aggravating the
stress response as reported by several studies (Type D stress
inflammation). It is now widely accepted that Type D personality is
associated with coronary heart disease, thus strengthening the
psychobiological links between behavior, stress reactions and the
somatic consequences [17]. In addition, the Five-Factor Model of
personality defined psychological variations of the normal person-
ality in the 1990s [18]. Thanks to clinical and statistical
measurements, a Five-Factor model of personality was obtained,
the following five independent factors: extraversion, agreeableness,
conscientiousness, openness and neuroticism. In terms of stress
reaction and management, the 5-Factor Model showed that
extraversion, openness and mainly conscientiousness were protec-
tive dimensions in terms of health that depended on direct and
indirect causality. Several prospective studies demonstrated, for
instance, that conscientiousness was directly associated with lower
systemic inflammation, which may explain the better health and the
lower frequency of metabolic syndrome and cardiovascular events
in such people [19,20]. Psychobiological mechanisms of stress might
be regulated in a protective way in some people with positive,
dynamic personalities, whereas negative coping strategies may
induce deleterious stress responses. In addition, personality traits,
such as conscientiousness, could be indirectly associated with better
somatic outcomes because of protective behavior. Indeed, consci-
entious people are good at formulating long-range goals, organizing
and planning routes to these goals, and working consistently to
achieve them despite difficulties. Then, conscientious people
generally listen to health advice, maintain a balanced diet and
comply with medical treatments, all of which could indirectly
explain better outcomes in such people. In addition, several studies
have shown that personality may be associated with health
behavior, for instance, conscientiousness was associated with less
dangerous behavior (smoking, unbalanced diet, etc.). Numerous
arguments thus support the notion that personality traits may
modulate psychobiological stress response and health behavior. In
this context, paying attention to patients’ personality traits may be
important in order to take advantage of motivated personalities to
tailor care or to stimulate under-motivated people.
3.2. Emotional psychiatric disturbances
Besides normal psychological variations of personality or
coping styles, emotional disturbances can adversely affect people
with cardiovascular diseases. Indeed, numerous authors have
described the deleterious relationship between anxiety or
depression and cardiovascular disease. From an epidemiological
viewpoint, between 20 to 30% of depressive people show
symptoms of CHD [21]. As previously discussed, direct and
indirect mechanisms may mediate the impact of mood disorders
on cardiovascular disease. Indeed, major depression is sometimes
the cause of psycho-behavioral disturbances such as a loss of
interest in carrying out simple tasks (preparing meals, physical
activity), which explains the poor lifestyle habits of depressed
patients, who cannot summon up enough energy or motivation to
consider stopping smoking or changing to a well-balanced diet or
maintaining regular physical activity. Depression may occur at any
time during a person’s history of heart disease, and is a behavioral
factor in the development or aggravation of heart disease as the
patient adopts a prolonged sedentary lifestyle, experiences a
decline in psychological and physical motivation and tends not to
respect the therapeutic regimen. From a biological viewpoint, the
9
stress response could be responsible for cardiac disturbances.
During an episode of characterized depression, which in itself is a
major factor of stress, the hypothalamic-pituitary-adrenal axis is
strongly activated; an increase in serum levels of cortisol and
cortisol urinary derivatives indicate the initiation of anti-inflam-
matory processes that try to restore the disturbed homeostasis
[21,22]. This chronic hypercortisolemia could correlate with the
development of atherosclerosis and reflect another biological
similarity between depression and heart disease. Indeed, inflam-
matory pathways may be involved in the association between
emotional disturbances and cardiac events via the stress reaction.
The inflammatory hypothesis is becoming more and more robust
as blood markers of inflammation [23,24] have been found in both
depression and heart disease. In parallel, a decrease in serum levels
of Omega-3-type polyunsaturated fatty acids, which has anti-
inflammatory properties, has also been observed in depression and
cardiovascular disease [25]. The powerful psychological stress
associated with mood disorders may cause chronic low-grade
inflammation, which is known to be associated with coronary
heart disease. Inflammatory processes involved in both mood
disorders and cardiovascular disease may be illustrated by lipid
dysregulation. For instance, low HDL-cholesterol has been
associated with depressive disorder [26]. In addition, molecular
and genetic factors linked to oxidative stress and cellular
senescence are implicated in anxiety and depression and may
exacerbate cardiac disturbances (Fig. 3) [27,28]. Moreover, genes
involved in protection against oxidative stress were up-regulated
in anxious and depressed people, thus demonstrating a link
between the intensity of anxiety/depression and cellular damage
[28]. Other authors have developed evolutionary theories showing
that the human genomic system of response to adversity is
effective in managing acute stress but not chronic social stress. As
this system is not adapted to dealing with contemporaneous stress,
the stress response fails and triggers chronic inflammatory
activation and metabolic disturbances [29].
There is an accumulation of robust scientific evidence showing
direct and indirect pathophysiological links between personality,
stress response, anxiety/depression and cardiovascular disease. In
this context, paying attention to psychological and psychiatric
aspects seems particularly important in order to improve
cardiovascular outcomes, and cardiac rehabilitation is probably
the right place and the right time to tackle psychological issues in
people with cardiac disease.
3.3. Diagnosis of emotional disturbances in patients with heart
disease
First, the diagnosis of psychiatric disorders such as anxiety or
depression appears to be crucial. For rehabilitation to be effective
in heart disease patients, they need to have a rather good
psychological status. The first task of the clinician is to detect
emotional troubles such as anxiety and depression. Many studies
have highlighted the fact that these psychiatric aspects are
underdiagnosed in patients with cardiovascular disease, even
though such problems are crucial. In order to optimize screening
for affective disorders, certain cardiology or cardiac rehabilitation
units routinely use standard self-questionnaires such as the Beck
Depression Inventory or the Hospital Anxiety and Depression scale
[30,31], which give an overall idea of the severity of the anxio-
depressive episodes sometimes found in patients suffering from
heart disease. However, these psychometric tools do not replace
the clinical interview and are not standardized automatic
providers of psychiatric diagnoses, but they do reveal certain
emotional disorders, and may confirm a clinical impression, or
they simply facilitate discussions between the doctor and the
patient.
10 J.-C. Chauvet-Gelinier, B. Bonin / Annals of Physical and Rehabilitation Medicine 60 (2017) 6–12
Fig. 3. Psychological stress, inflammation, oxidative stress, cellular senescence and cardio-metabolic diseases [20,23,26].
Concerning the pharmacological treatment of anxiety and
depression, tricyclic antidepressants, which cause potentially
dangerous adverse effects (rhythm disorders), are no longer the
molecules of choice in this context. Several studies have shown
that the new generation of antidepressants, in particular selective
serotonin reuptake inhibitors, are globally well tolerated, have a
satisfactory efficacy-tolerance profile and are easy to use in
patients suffering from cardiovascular disease [32]. In addition,
these molecules show clinical efficacy and act on pathophysiologi-
cal elements by improving endothelial function while reducing
levels of inflammation markers (CRP, IL-6) [33]. In the same way, a
meta-analysis by Mazza showed that selective serotonin reuptake
inhibitors used in the wake of an acute coronary syndrome led to
fewer re-hospitalizations [34]. It therefore appears important to
underline the recommendation that antidepressants should be
prescribed for a minimum of 6 months in the first episode of
depression, this period can be extended in cases of recurrent
episodes. Concerning the precautions of use, despite the remark-
able acceptability of this new generation of antidepressants,
particular attention must be paid to potential drug interactions
between antidepressants and cardiovascular drugs, without
forgetting to take account of the metabolic pathways involving
p450 cytochromes. It is also important to remember that certain
molecules may lengthen the QT interval [35]. As a complement to
the pharmacological treatment, any form of psychotherapy seems
beneficial in that it allows the patient to speak to an attentive
listener. However, in the scientific literature, only cognitivo-
behavioral-type therapies have been evaluated in a standardized
manner, and have been shown to be of interest in heart disease.
These pragmatic techniques for psychological support, which show
a beneficial effect rather quickly, provide relevant help in stress
management. On this subject, various studies have shown that a
reduction in psychosocial stress could increase life expectancy
after coronary artery bypass graft in victims of myocardial
infarction [36]. Whatever the method employed, considerate
empathy can certainly help the patient through possible reorgani-
zation of his/her existence and the frequent modifications in
lifestyle, which are sometimes radical and difficult to accept
(smoking cessation, diet changes, reconditioning to physical
effort). Strategies involve helping the patient to preserve the
positive dynamic traits of his/her functioning while modifying the
potentially dangerous negative aspects for the heart such as
hostility, excessive pessimism or any attitude likely to trigger a
harmful psychobiological response to different factors of stress. It
was thus shown that reducing inappropriate responses to factors of
stress led to beneficial effects for both the heart and the
psychological state [37]. Follow-up as an outpatient in a cardiac
rehabilitation unit is an excellent way for patients to recover
physical and psychic equilibrium by better understanding of their
heart function, progressive reconditioning to effort, gradually
learning the new rules for hygiene and diet, and by gaining access
to professionals in psychological care [38–40]. Finally, particular
attention should be paid to coronary patients suffering from
characterized depression who do not respond to medical
treatments and psychotherapy since several clinical trials have
shown that resistance to treatment for depression is a risk factor
for recurrent cardiovascular events and subsequent death [41,42].
3.4. Stress management, positive psychology and cardiac
rehabilitation
In a context where the response to stressful events plays a
dramatic role as a risk factor for heart disease any intervention that
aims to reduce stress may be interesting. However, recent data
concerning psychological interventions for people with heart
disease show that psychological interventions only moderately
improve emotional disturbances like anxiety or depression. And
the impact of stress management interventions on cardiac
morbidity or mortality appeared modest. Some studies, however,
have shown that psychological information and brief psychother-
apy concerning stress reduction, coping strategies and cognitive
and behavioral strategies can be useful in this field, mainly in the
short term just following the acute phase of the disease (i.e. in
cardiac rehabilitation programs). Indeed several studies demon-
strated that stress reduction was associated with improved cardiac
outcomes. In this field, positive psychology may be an interesting
cognitive and behavioral therapy for patients. Indeed, positive
affectivity was shown to be associated with better treatment
 J.-C. Chauvet-Gelinier, B. Bonin / Annals of Physical and Rehabilitation Medicine 60 (2017) 6–12
adherence and cardiac rehabilitation adherence [43]. Positive
psychological functioning, like positive affect and optimism,
stimulates goal-striving activities, which may sustain all cognitive
and behavioral strategies to cope with cardiovascular disease, to
adopt protective health behavior and to adhere to therapies.
Moreover, in depression associated with chronic heart failure,
positive affect could moderate the deleterious effects of depression
and anhedonia [44]. Cardiac rehabilitation could therefore be the
right moment to implement psychological interventions in order
to stimulate psychological well being and disease acceptation and
to reduce anxious or depressive symptoms. Now that there is
strong scientific evidence linking emotional disturbances with
heart dysfunction it is probably time to develop global approaches
to care in patients with cardiovascular disease so as to improve
psychological and cardiac outcomes [45].
4. Conclusion
Psychological determinants are now regarded as important
factors that influence health in general and cardio-metabolic
pathways in particular. Indeed, the biological, psychological and
cognitive response to chronic stress may play a role in heart
disease as a trigger or as an independent factor influencing cardiac
outcomes. There is now considerable robust scientific evidence in
support of this hypothesis, and it is now time to take account of this
psychobiological interplay. In this context, cardiac rehabilitation
appears to be the right time to manage psychological disorders in
heart disease patients, in order to help them reduce the deleterious
effects of stress on their minds and bodies. Further studies are
necessary to explore the impact of psychological therapy on
cardiac outcomes in patients with cardiac disease.
Funding sources
None.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgments
We are grateful to Philip Bastable for the English revision of the
manuscript.
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