Journal of Clinical Neuroscience xxx (2017) xxx–xxx

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Journal of Clinical Neuroscience

journal homepage: www.elsevier.com/locate/jocn

Review article

Depression and cardiovascular disease in elderly: Current understanding

Yaxin Zhang a, Yujing Chen b, Lina Ma a,⇑
a
Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing Institute of Geriatrics, China National Clinical Research Center for Geriatric Disorders, Beijing
100053, China
b
Department of Traditional Chinese Medicine, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China

a r t i c l e i n f o a b s t r a c t

Article history: Geriatric depression is a major public health problem and has an especially large effect on health when
Received 14 August 2016 comorbid with a chronic medical condition. Hypertension, coronary heart disease, and diabetes are
Accepted 29 September 2017 accompanied by a high incidence of depression and can affect the treatment and prognosis. Depression
Available online xxxx
is a highly prevalent risk factor for incident of and is associated with morbidity and mortality of cardio-
vascular disease. In addition to the proactive and effective control of primary diseases, efforts should also
Keywords: be made to improve patients’ psychological and social function. Current evidence on antidepressive ther-
Depression
apy in patients with coronary diseases is limited. A better understanding of pathophysiological mecha-
Cardiovascular disease
Elderly
nisms underpinning depression and cardiovascular disease as well as the complex biological crosstalk
of cardiovascular disease complicated with depression is particularly important for future therapeutic
strategies. The following review is on current understanding of geriatric depression and cardiovascular
disease.
Ó 2017 Elsevier Ltd. All rights reserved.

1. Introduction
As the number of old people throughout the world increases,
senescence-related issues become increasingly important. A major
current challenge is maintaining mobility and quality of life into
old age. Hypertension, coronary heart disease, diabetes and other
cardiovascular diseases (CVD) are psychosomatic diseases, and
psychological factors play an important role in the occurrence
and development [1–3]. Geriatric depression is a major public
health problem and has an especially large effect on health when
comorbid with a chronic medical condition [4,5]. With the rapid
aging of the population, the prevalence rate of geriatric depression
increases fast. The prevalence rate of depression is up to 50% in
patients with chronic disease [6]. Depression leads to a variety of
functional somatic disorders, and seriously affects the attitude of
treatment in patients with diseases, so that reduce the quality of
life [7]. Depressive frequently occurs due to comorbid medical con-
ditions such as thyroid disease, diabetes, cardiac disease, and other
chronic medical conditions [8–11], and can predict CVD and
all-cause mortality independently of a wide range of potential
confounders [11]. But at present, most patients with geriatric
depression are clinically undiagnosed and lack sufficient support
⇑ Corresponding author at: Department of Geriatrics, Xuan Wu Hospital, Capital
Medical University, China National Clinical Research Center for Geriatric Disorders,
#45 Changchun Street, Xicheng, Beijing 100053, China.
E-mail address: malina0883@126.com (L. Ma).
from their family members and the community. As two of the most
leading causes of death and disability, however, little is known
regarding the link between the geriatric depression and CVD as
well as the secondary prevention. A few clinical trials focusing on
the prevention of depression were found to decrease the risk of
cardiac events, while further clinical trials are needed to test
well-defined mental health interventions [1,12]. Therefore, a better
understanding of comorbid CVDs and depression is particularly
important for improving CVD management in older adults and thus
achieving a healthy aging of society.
2. Epidemiology
Depression is a mood disorder characterized by listlessness and
slow thinking, which can be accompanied by psychomotor retarda-
tion symptoms including a loss of interest in normal activities.
Along with aging, the physiological and psychological functions
of older adults become weakened; in particular, the sensory organs
and nervous system involved in psychological activities can expe-
rience degenerative changes. The metabolism of the nervous sys-
tem and changes in some neurotransmitters are the
pathophysiological basis of geriatric depression. In addition, the
changes in social roles, social environment, and family circum-
stances, as well as life events such as somatic illness and death
of a spouse, can render older adults more susceptible to geriatric
depression. Because of differences in screening tools and survey

https://doi.org/10.1016/j.jocn.2017.09.022
0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Zhang Y et al. Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci (2017), https://
doi.org/10.1016/j.jocn.2017.09.022
2 Y. Zhang et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
samples, the prevalence of depression dramatically differs world-
wide [13–15], for example, community-based studies in older
adults have shown that the prevalence of depression was 33.5%
in Japan but 17.6% and 14.6%–17.2% in the United Kingdom and
the United States, respectively [13–15].
The prevalence of depression is 15–20% in CVD [16,17]. Major
depression was present in 19.8% in patients with acute myocardial
infarction, and 31.1% of these patients with previous myocardial
infarction had clinically significant depression [18]. The prevalence
of depression in hypertensive patients was 40.1% [19]. According to
Bensenor et al., the incidence of depression was as high as 63.4% in
hypertensive women and 36.6% in hypertensive men [20]. The inci-
dence of depression increases remarkably in hypertensive patients.
Using the general Quality of Life Scale, Jonas et al. found that
depression symptoms were associated with an increased incidence
of hypertension [21]. Depression not only is a contributor to hyper-
tension but also may affect the outcomes and prognosis of hyper-
tension and the efficacy of drugs.
3. Relationship between CVDs and depression in the elderly
Chronic diseases such as CVDs can affect older people’s self-
rated health and cognitive functions and thus cause somatic dys-
function, which can trigger and exacerbate the occurrence and
development of geriatric depression. Also, depression can induce
or worsen chronic diseases and affect prognosis. A large (60% to
80%) increased the risk of coronary heart disease was found to be
associated with depression [2]. CVDs have a long disease course
and require long-term medications, during which persistent com-
plications, decline in physical functions, heavy financial burden,
and increased dependence on other people will remarkably
increase depression symptoms in older adults [22]. However,
research has also suggested that hypertension and diabetes are
not associated with an increased risk of depression [23].
3.1. Depression and hypertension
Depression was associated with hypertension [24]. A meta-
analysis found that depression increased the risk of hypertension
incidence, furthermore, the risk was significantly correlated with
the prevalence of depression at baseline [25]. Clinical and epidemi-
ological studies have shown that the presence of depression and its
severity were closely related to the prognosis of hypertensive
patients. The morbidity and mortality rates of myocardial infarc-
tion, stroke, sudden death, and other severe cardiovascular events
increase in patients with depression [26,27]. Adamis et al. found
that the incidence of hypertension increased in patients with
depression, and the depressive mood was associated with
increased blood pressure levels [28]. However, some other studies
did not find any link between depression and high blood pressure
[29]. Insufficient recognition of different pathways linking depres-
sive symptoms with blood pressure, hypertension and related
medications may lead to the disparity [30].
3.2. Depression and coronary heart disease
In healthy populations, depression increases the risk of coro-
nary artery disease by 1.5–2.0 times; in patients with coronary
artery disease, depression increases the risk of myocardial infarc-
tion by 1.5–4.5 times [31–33]. Depression is associated with a
higher incidence of coronary heart disease [34], and a greater num-
ber of recent stressful life events elevate the risk of new-onset CVD
[15]. Furthermore, psychometric evaluation of depression is
related to the frequency of chest pain in patients with or without
coronary artery disease in a prospective cohort study [35].
Please cite this article in press as: Zhang Y et al. Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci (2017), https://
doi.org/10.1016/j.jocn.2017.09.022
Recently, some global studies have found that positive emotions
can reduce the 10-year incidence of coronary heart disease [36].
A study in the United States found that low blood pressure was
associated with high scores of positive emotions [37].
3.3. Depression and diabetes
The incidence of depression has been reported to reach 8.5–
27.3% in diabetic patients [38,39]. A prospective study has indi-
cated that diabetes increased the risk of depression by 1 time; fur-
ther analysis showed that psychological disorders and diabetes
may exacerbate each other. Depression can inhibit the secretion
of pancreatic islet cells, thus reducing the glucose metabolism-
regulating capability in diabetic patients [40], thus leading to a
high mortality risk [41].
3.4. The clinical screening tool for geriatric depression
Most studies have confirmed the positive relationship between
CVDs and depression. However, comparison among these studies is
often difficult because of the following reasons: lack of uniform/s-
tandardized screening tools; lack of nationwide large-scale sur-
veys; some studies were based on self-rated hypertension; lack
of systematic adjustment of the underlying confounding factors;
and lack of standardized diagnostic criteria for mental disorders
[42]. Currently, no internationally recognized screening tool has
been available for assessing depression. The commonly used clini-
cal scales for screening for early geriatric depression include the
Geriatric Depression Scale (GDS), Center for Epidemiologic Studies
Depression Scale (CES-D), and Beck Depression Inventory (BDI).
The GDS is mainly designed for older adult populations, whereas
the CES-D is more suitable for large-scale epidemiological surveys
across a range of age groups. A recent study found that CES-D in
useful to screen for both depression and anxiety disorders in
patients with coronary heart disease [43]. In addition, the Hamil-
ton Rating Scale for Depression, Self-Rating Depression Scale, and
Depression Questionnaires are often used for clinical diagnosis
and assessment [44].
4. Potential mechanisms governing the impact of depression on
CVDs
The impact of depression on CVDs in older adults may be
related to the following four factors: impaired heart rate variabil-
ity, systemic chronic inflammation, Hypothalamic–pituitary–adre
nal (HPA) axis dysfunction and endothelial dysfunction. Such
mechanisms are not only associated with complications in the
advanced stages of the disease but also may speed up the connec-
tion between depression and CVDs in the initial stages [45].
4.1. Impaired heart rate variability
Heart rate variability was considered as a marker of vagal activ-
ity [46]. Some studies observed the relationship between impaired
autonomic function and severity of coronary artery disease, which
indicated that abnormal heart rate variability-related depression
might trigger early atherosclerosis and/or speed up its progression
via platelet aggregation, irritable inflammation, and changes in
lipid metabolism [47]. In addition, imbalanced heart rate variabil-
ity may increase coronary heart disease mortality and accelerate
coronary atherosclerosis in depressive patients by inducing
myocardial ischemia, ventricular dysrhythmias, and sudden death,
and is associated with post-infarct mortality [48–50].
 Y. Zhang et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
4.2. Systemic chronic inflammation
The activation of inflammation can increase the resetting of the
autonomous systems and the endothelium-dependent responses
in human blood vessels in depressive patients [51]. Depression
was independently associated with low-grade inflammation onset
among healthy individuals [52]. Interleukin-6 (IL-6) and C-reactive
protein (CRP) were the two important biomarkers of systematic
inflammation, and they might be mechanisms contribute to CVD
[53]. Furthermore, research has found that IL-6 and CRP are indica-
tive of atherosclerosis, and probably predictive for atherosclerosis
[54]. The inflammatory cytokines, chemokines, and acute phase
proteins were found to be elevated in the peripheral blood, central
nervous system and cerebrospinal fluid in patients with depression
[55].
4.3. HPA axis dysfunction
Several studies have found that the levels of cortisol were ele-
vated in patients with depression, which indicates HPA axis is a
very important cause of depression induced by psychological stress
[56–59]. It has been suggested that the dysfunction of the HPA axis
may also contribute to the pathogenesis of depression and comor-
bid CVD [60,61]. As one of the most consistent biological findings
in major depression [62], it was observed that in depressed
patients, HPA axis dysregulation not only reduces hippocampal
volumes and prefrontal cortex activity but also disrupts homeosta-
sis within the neurocircuit of depression [63]. Furthermore, the
high level of cortisol is also considered to be associated with an
increased risk of glucose intolerance, hyperlipidemia, which were
risk factors for hypertension, coronary heart disease and so on
[64–66]. From this aspect, the potential therapeutic benefits of
antiglucocorticoids should be considered, as the current pharma-
cological treatment of depression is far from perfect [62].
4.4. Endothelial dysfunction
Endothelial dysfunction can be detected in the earliest stages of
the atherosclerotic, and it is associated with many cardiac risk fac-
tors [67], thus, the endothelium is a crucial element for vascular
health [68] and can be detected before the occurrence of CVD
[68]. Evidence indicates that depression is associated with
endothelial dysfunction, even in the absence of other cardiac risk
factors [69–71]. A recent study used flow-mediated dilatation
(FMD), von Willebrand factor, soluble intercellular adhesion mole-
cule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble
thrombomodulin and soluble endothelial selectin (sE-Selectin) as
biomarkers of endothelial dysfunction, and found that the
endothelial dysfunction plays an important role in the pathobiol-
ogy of depression [72].
4.5. A complex biological crosstalk
The underlying mechanism linking depression and CVD are
multifactorial. There may be a complex biological crosstalk among
the impaired heart rate variability, systemic chronic inflammation,
HPA axis dysfunction and endothelial dysfunction. The dysfunction
of HPA axis is deduced to be reciprocally regulated by altered
expression of pro-inflammatory cytokines and is also related to
endothelial dysfunction [73,74] and pro-inflammatory cytokines
[75–77]. Dysregulation of the HPA axis may also lead to sympa-
thoadrenal hyperactivity, thus an increase in heart rate and plate-
let activation which drive the disease to CVD [61,78]. Another
study found that inflammation biomarkers such as hsCRP, tumour
necrosis factor-a (TNF-a), serum amyloid A, sICAM-1 and endothe-
lial dysfunction biomarkers sICAM-1, sE-Selectin were univariately
Please cite this article in press as: Zhang Y et al. Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci (2017), https://
doi.org/10.1016/j.jocn.2017.09.022
3
associated with depressive symptoms and depressive disorder,
independent of lifestyle factors [79], which indicates inflammation
and endothelial dysfunction are both associated with depression. A
recent critical review summarized the relevant markers of depres-
sion in patients with CVD, including TNF-a, FMD, endothelin-1,
endothelial progenitor cells, brain-derived neurotrophic factor,
and docosahexaenoic acid [80]. Interestingly, depressive symp-
toms were only associated with CVD mortality in men adjusted
for other factors [81], which indicates that there might be gender
differences in depression biomarkers [79].
5. Impact of clinical antidepressant treatment on older patients
with CVDs
An international study with a large sample size showed that
depression was not only an independent risk factor for CVD deaths
and suicide but also a risk factor for deaths from all serious dis-
eases [82]. An analysis of a sample of nurses’ health showed that
depression was linked to morbidity and mortality of CVDs in
female subjects without a history of coronary heart disease, and
the depression symptoms were directly associated with the risk
of coronary events. In addition, the depression symptoms had the
strongest association with fatal coronary heart disease, and such
an association persisted even after other risk factors for coronary
heart disease were controlled [83]. Depression symptoms were
associated with surrogate indicators of fatal coronary heart disease
and clinical depression, and the use of antidepressant drugs signif-
icantly increased the incidence of sudden cardiac death. The
impact of psychological factors on CVD patients is becoming
increasingly recognized. Many interventions have been adopted
in this regard. In addition to health education and psychological
support/treatment, anti-depression therapy can facilitate treat-
ment [84]. In hypertensive patients complicated with depression,
the combination of antihypertensive drugs and antidepressants
not only alleviates the depression symptoms but also changes
the patients’ attitudes towards treatment; thus improving medica-
tion compliance and increasing blood pressure control rate.
Data from the REGARDS study suggested that antidepressant
use was associated with a small increase in all-cause mortality,
after adjusting for covariates [85]. According to Almeida OP et al.
[86], the risk of death was higher in male patients with CVDs than
those without CVDs, and the mortality rate remarkably increased
in patients with depression than in those without depression.
The interaction between depression and CVDs had no significant
effect on mortality, indicating that the successful management of
a CVD may not necessarily reduce the risk of death due to depres-
sion, and vice versa.
Recent research has shown that the application of conventional
antidepressant drugs can increase all-cause mortality, which may
be explained by the adverse reactions of the antidepressant drugs.
A cohort study with a large sample size found that, compared with
healthy controls, depressed patients had significantly lower sys-
tolic blood pressure and were less susceptible to isolated systolic
hypertension. Compared with healthy controls and treatment-
naive patients, patients who had been treated with tricyclic antide-
pressants (TCA) had higher systolic and diastolic blood pressure
and were more likely to develop clinical hypertension (grade 1 or
2). Such effects are partially achieved by controlling cardiac stimu-
lation by the vagus nerve. During the treatment of patients with
anxiety or depression, especially in patients with concomitant
CVDs, selective serotonin reuptake inhibitors (SSRIs) may be the
preferred option [87]. If no such clinical efficacy is achieved, TCA
as well as adrenergic and serotonergic drugs may be administered
under close blood pressure monitoring [87]. Two cohort studies
have found that the relationship between cardiac vagal inhibition
4 Y. Zhang et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
and depression/anxiety was affected by the use of antidepressants
[88,89]. The cardiac vagal inhibition remarkably decreased in
patients who had used TCA, SSRIs, and/or serotonergic drugs. Par-
ticularly, the heart rate increased in patients who had been treated
with TCA [89,90]. Recent studies have found that the administra-
tion of TCA was associated with higher risk of CVDs, whereas no
such association was found for SSRIs [91]. The increased risk of
CVDs after the use of TCA cannot be explained by the known men-
tal disorders, suggesting the antidepressant treatment with TCA
created extra disease burden. However, on one hand, little evi-
dence indicates that treatment for depression is less effective in
patients with coronary heart disease [92], on the other hand, the
few clinical trials which focused on the cardiac outcomes of
depression treatment lacks positive results, hence, whether
depression might be an appropriate therapeutic target for these
patients was rather controversial [93] and further clinical trials
are needed.
6. Conclusion
In summary, depression emerges as a relevant cardiovascular
risk factor and the combination of depression and CVDs leads to
worse health outcomes and has a large impact on public health.
Hypertension, coronary heart disease, and/or diabetes are accom-
panied by a high incidence of depression, at the mean while, there
is a strong association between depression and cardiovascular risk.
Unfortunately, such a situation has not been well recognized in
clinical settings, which may affect the treatment and prognosis of
CVDs. Current evidence on antidepressive therapy in patients with
coronary diseases is limited, which indicates new high-quality tri-
als should be carried out to decrease the morbidity and mortality
of CVDs [12]. A better understanding of pathophysiological mech-
anisms underpinning depression and CVD as well as the complex
biological crosstalk of CVDs complicated with depression is partic-
ularly important for future therapeutic strategies. In addition to
the proactive and effective control of primary diseases, efforts
should also be made to improve patients’ psychological and social
functioning. Under the biopsychosocial model, early identification
and rational intervention of depression will help to improve qual-
ity of life, increase life expectancy, and lower medical costs.
Conflict of interest
None declared.
Acknowledgements:
This work was supported by the following grants: Beijing Nat-
ural Science Foundation (7174310), Beijing Municipal Administra-
tion of Hospitals’ Youth Programme (QML20160804,
QML20160805), and Beijing Municipal Administration of Hospitals
Clinical Medicine Development of Special Funding Support
(ZYLX201706).
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