Associations between life stress and subclinical cardiovascular disease are partly

mediated by depressive and anxiety symptoms

Stress experienced during childhood or adulthood has been associated with

cardiovascular disease (CVD), but it is not clear whether associations are
already prevalent on a subclinical cardiovascular level.
This study investigates associations between indicators of life stress and
subclinical CVD, and whether these are mediated by depression and anxiety.
Life stress included childhood trauma, negative life events and recently
experienced daily hassles or job strain. Subclinical CVD was measured as 1)
carotid atherosclerosis (intimamedia thickness and the presence of plaques)
using B-mode ultrasonography, and 2) central arterial stiffness (heart rate
normalized augmentation index) using calibrated radial applanation
tonometry.
Increased central arterial stiffness was shown in subjects who had
experienced childhood trauma (per SD increase: = .07; p = .01), or
reported recently experienced daily hassles (per SD increase: = .06; p = .
02), negative life events (per SD increase: = .05; p = .03), or job strain
(high versus low: = .09; p = .01). Associations between life stress and
arterial stiffness appeared to be partly mediated by severity of depressive
and anxiety symptoms. No significant associations were found for childhood
life events, nor between indicators of life stress and carotid atherosclerosis
Childhood trauma and recent life stress were associated with increased
central arterial stiffness. This suggests that life stress partly via depression
and anxiety might enhance the development and progression of CVD.
Stressful circumstances during childhood and adulthood may also play a role,
although their precise contribution is unknown
Significant associations between life stress and arterial stiffness were partly
mediated by depression and anxiety.
Our finding that job stress was associated with increased arterial stiffness is
in line with one study in which demanding work was found to be positively
associated with stiffness. Also meta-analytic data have demonstrated that job
strain predicts higher CHD incidence
This might indicate that life stress leads to arterial stiffness through the
development of depressive and anxiety disorders. A possible explanation for
the strong direct effect between job strain and arterial stiffness, which is
independent of lifestyle and psychopathology, is an altered autonomic tone
with more sympathetic and less parasympathetic activity. This may lead to
metabolic dysregulations in general [53] and accentuated inflammation of
the arterial wall and as a consequence to the formation of thrombosis
We found no significant associations between either childhood or recent life
stress and carotid atherosclerosis. This is consistent with previous research in
this sample [42], in which no significant associations were found between
depressive and anxiety disorders and carotid atherosclerosis.
Increased fibrinogen responses to psychophysiological stress predict future
endothelial dysfunction implications for cardiovascular disease?

Acute mental stress can induce both low-grade inflammation and endothelial
dysfunction. The relationship between inflammatory responses to stress and
future endothelial function is unexplored.
We investigated the relationship between inflammatory responses to an
acute mental stress challenge and endothelial function plus the influence of
dyslipidaemia on the associations.
there was an interaction between the presence of dyslipidaemia and
immediate change in fibrinogen with stress which was associated with FMD.
Those participants with dyslipidaemia who had a greater change in fibrinogen
had lower FMD. We conclude that elevated fibrinogen responses to stress are
associated with future endothelial dysfunction which may reflect increased
cardiovascular risk
The main finding of this study is that those participants who had a higher
fibrinogen response to a psychophysiological stress challenge had less well
preserved endothelial function when assessed 3 years later following
adjustment for key relevant cardiovascular risk factors

Associations of chronic stress burden, perceived stress, and traumatic stress with
cardiovascular disease prevalence and risk factors in the HCHS/SOL Sociocultural
Ancillary Study

The current study examined multiple stress indicators (chronic, perceived,

traumatic) in relation to prevalent coronary heart disease (CHD), stroke, and
major cardiovascular disease (CVD) risk factors (i.e., diabetes, dyslipidemia,
hypertension, current smoking) in the multi-site Hispanic Community Health
Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study
Chronic stress burden was related to a higher prevalence of CHD after
adjusting for sociodemographic, behavioral and biological risk factors [OR
(95% CI) = 1.22, (1.101.36)] and related to stroke prevalence in the model
adjusted for demographic and behavioral factors [OR (95% CI) = 1.26, (1.03
1.55)]. Chronic stress was also related to a higher prevalence of diabetes
[OR=1.20, (1.111.31)] and hypertension [OR=1.10 (1.021.19)] in
individuals free from CVD (N=4926). Perceived stress [OR=1.03 (1.011.05)]
and traumatic stress [OR=1.15 (1.051.26)] were associated with a higher
prevalence of smoking. Participants who reported a greater number of
lifetime traumatic events also unexpectedly showed a lower prevalence of
diabetes [OR=.89 (. 83.97)] and hypertension [OR=.88 (.82.93)]. Effects
were largely consistent across age and sex groups.
stress is a complex multi-dimensional construct that is challenging to
operationalize
 In models that adjusted for demographic and behavioral indicators, each
additional chronic stressor reported was associated with increased odds of
diabetes and hypertension of 20% and 14%, respectively
Perceived stress was associated with a small increase in odds of current
smoking (3%), but did not relate to other CVD risk factors
For traumatic stress, the expected positive association was found with
smoking, so that each additional traumatic stressor reported was associated
with a 15% increased odds of current smoking

State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease

Recently, large prospective epidemiologic studies and smaller basic science studies
have firmly established a connection between CVD and several psycho -logical
conditions, including depression, chronic psychological stress, posttraumatic stress
disorder (PTSD), and anxiety
In terms of common, daily stressors that may be experienced over prolonged
periods, meta-analyses of prospective observational studies found that social
isolation and loneliness were associated with a 50% increased risk of incident
CVD events (pooled relative risk = 1.5, 95% CI: 1.21.9).39 The increased risk
associated with work-related stress was similar at 40% (pooled relative
risk = 1.4, 95% CI: 1.21.8).3
. In a study of 281 Vietnam-era veteran twin pairs, Vaccarino et al.48 found
patients with PTSD had over twice the risk of increased incident CHD events
during an average of 13 years of follow-up and that this association was
independent of traditional CVD risk factors, depression, and substance abuse
or dependence. Importantly, the authors also found those with PTSD had
decreased myocardial blood flow on cardiac positron emission tomography
scans
Another study of 637 veterans without known coronary artery disease found
those with PTSD had higher levels of coronary artery calcium, a marker of
atherosclerosis, on computed tomography scans.

Stress and Atherosclerotic Cardiovascular Disease 391

Among these factors, stress is thought to be pivotal. Several types of stress

are involved in the development of cardiovascu- lar disease, including
oxidative stress, mental stress, hemodynamic stress and social stress.
Oxidative stress is implicated in the pathogenesis of endothelial dysfunction,
atherogenesis, hypertension and remodel- ing of blood vessels.
The cardiovascular system is constantly exposed to hemodynamic stress by
the blood flow and/or pulsation, and hemodynamic stress exerts profound
effects on the biology of vascular cells and cardiomyocytes.
 Stress - a noxious stimulus, such as the threat of a physical attack, chronic
discomfort or excessive physical activity.
a wide variety of stressors can induce similar processes, regardless of the
type of stimuli; he referred to this phenomenon as general adaptation
syndrome
There are three phases of general adaptation syndrome. The first is the alarm
or fight or flight response, which prepares the organism for the challenge of
the stressful stimuli. The second phase involves the chronic adaptation to a
stressful stimulus, while the final phase constitutes a state of fatigue, in
which the adaptive system begins to fail. More importantly, he reported that
the final stage of general adaptation syn- drome, wherein the adaptive
system is exhausted, results in nonspecific illness.
A large number of in vitro and in vivo investigations have provided evidence
that major atherosclerotic risk factors, such as diabetes, smoking,
hypertension and dyslipidemia, induce oxidative stress in the vascula- ture. In
fact, the generation of superoxide is enhanced in atherosclerotic vessels in
patients with unstable angina pectoris and atherosclerotic aortic aneurysms
In the vasculature, endothelial cells are constantly exposed to three kinds of
hemodynamic stress; shear stress, stretch forces and pressure.
It is known that stress responses resulting from hemodynamic forces exert
profound effects on the biology of vascular cells. In that study, the
relationship between mental stress and/or social factors and the incidence of
myocardial infarction was evaluated among 11,119 patients with a history of
acute myo- cardial infarction compared to 13,648 control sub- jects. The
results showed that the patients with a his- tory of myocardial infarction had
a higher prevalence of all types of mental and social stress, regardless of
ethnicity and gender. The odds ratio for depression was 1.38 (99% CI 1.19-
1.61), adjusted for age, gen- der, geographic region and the smoking status
Iso et al. analyzed the results of the Japan Collaborative Cohort Study for
Evaluation of Cancer Risk (JACC Study) Sponsored by the Min- istry of
Education, a large-scale cohort investigation, and clearly demonstrated that
perceived mental stress is associated with increased mortality due to stroke
and coronary heart disease)The results demonstrated that women with high
levels of stress have a two-fold higher age-adjusted risk of mortality due to
stroke and/or coronary heart disease than those who report low stress levels.
The mechanisms by which mental stress and/or depression induce or
exacerbate cardiovascular disease remain to be clarified. However, it is
necessary to con- sider such mechanisms from two different viewpoints, that
is, physiological and behavioral responses
In terms of physiological responses, two major systems are activated: the
sympathetic nervous system and the HPA axis. In addition to these two
systems, a wide variety of stress-responsive humoral factors, including
neurotrophins (NTs) and urocortin, have been reported to be dynamically
regulated.
 Lambert et al. evaluated the pattern of sym- pathetic nervous firing in
patients with metabolic syndrome and hypertension in relation to underlying
psy- chological stress and found that a higher incidence of multiple firing of
sympathetic nerves is associated with a higher level of affective depressive
symptoms
Activation of the sympathetic nervous system induces an increase in blood
vessel tone, myocardial oxygen consumption and platelet activation, followed
by acti- vation of the renin-angiotensin system (RAS)
The cortex of the brain perceives mental stress and then transmits signals to
the hypothalamus, where corticotropin- releasing factor (CRF) is released,
which binds to pitu- itary receptors, ultimately resulting in the release of
cortisol from the adrenal glands into the systemic cir- culation. Lipid and/or
glucose metabolism may be exacerbated due to the increased production of
corti- cal hormones induced by activation of the HPA axis

Work Stress as a Risk Factor for Cardiovascular Disease

This review of evidence from over 600,000 men and women from 27 cohort
studies in Europe, the USA and Japan suggests that work stressors, such as
job strain and long working hours, are associated with amoderately elevated
risk of incident coronary heart disease and stroke.
However, the obligation of minimizing excessive stress at workplaces is a
moral principle which is not dependent on the effects of work stress on
cardiovascular health.

Job Strain and Ambulatory Blood Pressure: A Meta-Analysis and Systematic Review

Single exposure to job strain in cross-sectional stud- ies was associated with
higher work systolic and diastolic ABP. Associations were stronger in men
than women and in studies of broad-based populations than those with
limited oc- cupational variance. Biases toward the null were com- mon,
suggesting that our summary results underesti- mated
Job strain is a risk factor for blood pressure eleva- tion. Workplace
surveillance programs are needed to assess the prevalence of job strain and
high ABP and to facilitate workplace cardiovascular risk reduc- tion
interventions.
Two major neuroendocrine systems are central to the stress response: the
sympathoadrenal medullary system and the hypo- thalamic---pituitary---
adrenal corti- cal system.

Platelet reactivity in prolonged stress disorders A link with cardiovascular

disease?

The impact of psychological disorders on cardiovascular health is

multifactorial, mediated by the dysregulation of the hypothalamicpituitary
 adrenal axis, sympathetic system and inflammation processes. Nonethe-
less, precise causality of stress-induced perturbations of cardiac and vascular
function is still poorly understood.
Increasing attention has been directed towards the role of platelets in the
chain of stress-related processes. Platelets possess a1- and a2-
catecholamines receptors, the stimulation of which leads to platelet
aggregation and thrombosis but inflammation and atherogenesis (e.g., via
CD40CD40 ligand pathway) are also promoted. Thus, excessive
sympathetic system activation may result in atherogenic effects. through
platelet activation, accompanied by P-selectin expression and direct
catecholamine-induced injury of the vascular wall. Thus, platelet dysfunction,
regulated in part by adrenaline, can influence the pathogenesis of CVD, as
has been extensively described in stress states

Relationship of Cardiovascular Disease to Stress and Vital Exhaustion in an Urban,

Midwestern Police Department

This study explored risk factors for cardiovascular disease (CVD) among 336
officers of a Midwestern police force. Instruments
The average vital exhaustion score was higher for female officers than male
officers (p < .05).
Compared to their civilian peers in the general population, police officers are
up to 1.7 times more likely to develop CVD
However, the difference in rates for hypercholesterolemia was statistically
significant by gender (46% for male vs. 23% for female officers; p < .01). The
relative risk of hypercholesterolemia for male officers, compared to female
officers, was 1.98 (95% confidence interval [CI], 1.10 to 3.56)

Occupational stress and hypertension

Occupational stress, or job strain, resulting from a lack of balance between

job demands and job control, is considered one of the frequent factors in the
etiology of hypertension in modern society.
It has been suggested that the formulations defining job strain, decision
latitude, and demands could influence the results: adding organizational
influence to the task-level decision latitude variables invariably produced a
stronger association between hypertension and job strain
Lucini99 reported reduction of job strain when an anti-stress program was
introduced at the workplace that reversed autonomic symptoms. Others have
emphasized the importance of managers stating clear goals, objectives and
lines of authority, in addition to providing proper training for the workers.25
Rosenthal et al100 reported a method of relaxation based on slow breathing
exercises that reduces BPa potentially useful tool at the work site and at
home.