Neurological Research

A Journal of Progress in Neurosurgery, Neurology and Neurosciences

ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20

Association between psychosocial stress and

hypertension: a systematic review and meta-
analysis

Mei-Yan Liu, Na Li, William A. Li & Hajra Khan

To cite this article: Mei-Yan Liu, Na Li, William A. Li & Hajra Khan (2017) Association between
psychosocial stress and hypertension: a systematic review and meta-analysis, Neurological
Research, 39:6, 573-580, DOI: 10.1080/01616412.2017.1317904

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Published online: 17 Apr 2017.

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Neurological Research, 2017
VOL. 39, NO. 6, 573–580
https://doi.org/10.1080/01616412.2017.1317904

Association between psychosocial stress and hypertension: a systematic

review and meta-analysis
Mei-Yan Liua, Na Lia, William A. Lib and Hajra Khanb
a
Department of Cardiology, Anzhen Hospital, Capital Medical University, Beijing, China; bDepartment of Neurosurgery, Wayne State
University School of Medicine, Detroit, MI, USA

ABSTRACT ARTICLE HISTORY

Aim: The etiology of hypertension is various and complex, involving both genetic and behavioral Received 19 December 2016
factors. The relationship between psychosocial stress and hypertension has been hypothesized. Accepted 23 March 2017
More and more people experience increased anxiety, depression, and chronic psychosocial
KEYWORDS
stress brought on by globalization, cultural changes, socioeconomic changes, and stress Psychological stress;
at the work place. Although a plethora of studies have investigated the interaction between hypertension; occupational
psychosocial stress and hypertension, this relationship is still contentious. The objective of this stress; anxiety; depression;
study is twofold. First, a review of recent advancements in our understanding of the relationship meta-analysis
between psychosocial stress and hypertension. Second, a meta-analysis aiming to assess the
relationship between chronic psychosocial stress and blood pressure.
Methods: We systematically searched and identified relevant studies from five databases,
including PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), CQVIP,
and the Wanfang Database until April 2016. Eleven studies encompassing 5696 participants
were included in the final analysis.
Results: Data showed that psychosocial stress was associated with an increased risk of
hypertension (OR = 2.40, 95% CI = 1.65–3.49), and hypertensive patients had a higher incidence
of psychosocial stress compared to normotension patients (OR  =  2.69, 95% CI  =  2.32–3.11).
Based on our meta-analysis, chronic psychosocial stress may be a risk factor for hypertension.
Conclusion: The few cohort and case-control studies on the association between psychosocial
stress and hypertension employed variable definition of stressors and the responses, making the
meta-analysis difficult. Although we found an association between chronic psychosocial stress
and hypertension, more studies are needed to confirm this relationship.

Introduction increases in blood pressure above 115/75 mm Hg; one

mmHg increase in systolic blood pressure increases
Hypertension constitutes an important public health
stroke mortality by 2% [8–12].
issue. Latest data predict that the number of hyperten-
Globalization and rapid social and cultural changes
sive adults will reach 1.5 billion – approximately 30%
have brought profound transformations to our social
of the world population – by 2025 [1]. The etiology of
organization, as well as new challenges that cause sig-
hypertension involves both genetic and behavioral fac-
nificant psychosocial stress. A large body of literature
tors, including age, race, positive family history, obe-
has accumulated evaluating the effect of psychologi-
sity, diet, sedentary lifestyle, and tobacco and alcohol
cal stress in several domains, including occupational
consumption [2,3]. Hypertension is notoriously diffi-
stress, economic/financial stress, stress associated with
cult to control and causes detrimental damage to the
racial discrimination, depression, and anxiety [13–17].
neuro- and cardio-vasculature. Frequent complications
A loose relationship between each of these aforemen-
of hypertension include atherosclerotic coronary artery
tioned domains and BP have been reported. However,
disease, congestive heart failure, stroke, intracerebral
the quality of the studies and the level of evidence varied.
hemorrhage, and chronic kidney disease. Hypertension
Numerous studies have been conducted investigating
is quantifiably the most significant risk factor for pre-
the association between psychosocial stress and hyper-
mature cardio- and neurovascular diseases, accounting
tension in recent years; however, variable definition of
for 47% of all ischemic heart disease events and 54%
stressors and responses were used from study to study,
of all strokes in the world [4,5]. Moreover, coronary
making generalization of the relationship between stress
disease in men and stroke in women are the primary
and hypertension difficult. For example, several stud-
causes of morbidity after hypertension onset [6,7]. The
ies showed that psychosocial stress influences blood
risk for stroke increases progressively with incremental

CONTACT  Mei-Yan Liu  china_lmy@hotmail.com

© 2017 Informa UK Limited, trading as Taylor & Francis Group
574   M.-Y. LIU ET AL.
pressure in women, but not in men [18]. The discrepancy
in the results are not clear, but one possible explanation
is the difference in the stressors that were being meas-
ured. Previous studies have shown that men are more
likely to cite poor work performance and job insecurity
as significant sources of stress, while women cite low sta-
tus at work as the most significant source of stress [19].
Additionally, other studies have concluded that there is
no significant relationship between stress and hyperten-
sion [20,21]. These studies are often plagued by cohort
selection and relatively small sample size. Therefore,
we believe it is imperative to evaluate the available data
and conduct a systematic review to determine whether
there is a relationship between psychosocial stress and
hypertension.
Various domains of stress defined
Occupational stress
Most adults spend a significant portion of time at work,
thus it is no surprise that occupational stress can have
a powerful impact on one’s health. Clinically, the most
commonly used model to measure job-related stress was
first proposed by Karasek et al. that encompasses two
major perimeters: workload and level of control. High
workload and low level of control leads to elevated occu-
pational stress [22]. Based on this model, a number of
longitudinal studies have concluded that high job strain
is associated with hypertension, including one demon-
strating job strain as associated with increased ambu-
latory blood pressure, sleep blood pressure, as well as
increased left ventricular mass [22–25]. Interestingly,
the effect of job strain on blood pressure is stronger
among men than women. Although the reason for this
difference is not clear, one possible explanation is that
men and women weigh different aspects of work stress
differently as mentioned earlier.
Socioeconomic status
Epidemiologic studies have consistently demonstrated a
negative linear correlation between occupational status,
income, and educational attainment with blood pres-
sure in low socioeconomic status cohorts. Low socio-
economic status is associated with chronically elevated
blood pressure, reduced nocturnal blood pressure dip-
ping, and delayed blood pressure recovery following
stress [26]. Strong evidence demonstrates the mecha-
nisms underlying the relationship between socioeco-
nomic status and high blood pressure include poorer
health behavior, financial stress, and fewer resources and
social safety net to cope with such stress.
Anxiety and depression
Anxiety and depression could be part of the maladap-
tive response to psychosocial stressors, and therefore
would be in the chain of causation of hypertension.
Patients with anxiety and/or depression represent a
particularly vulnerable cohort, as they are at increased
risk for developing hypertension. Anxiety is one of the
most pervasive psychiatric conditions in adults. Both
cross-sectional and longitudinal studies reveal a con-
nection between the risk of developing hypertension and
a spectrum of anxiety disorders, including generalized
anxiety, post-traumatic stress disorder and panic dis-
order [27]. Furthermore, the association between anx-
iety and hypertension seems to be bidirectional; those
with hypertension are more likely to have anxiety and
those with anxiety are at an increased risk to develop-
ing hypertension [28–32]. However, a few studies have
shown no association [21,33]. Nonetheless, coherent
mechanisms underlying anxiety-induced hypertension
have been elucidated and will be discussed in-depth in
the next section.
Depression and anxiety are closely linked. There is a
high prevalence of depression in hypertensive patients,
this prevalence was approximately nine times greater
than the general population per one study [34]. Similar
to anxiety, the association between depression and
hypertension is also bidirectional in nature. However,
the link between depression and hypertension is less
convincing compared to the association between anx-
iety and hypertension. One such study, Paterniti et al.
concluded that anxiety, but not depression, was inde-
pendently associated with an increased risk for high
blood pressure [35].
Mechanisms underlying psychosocial stress-
induced hypertension
The mechanisms underlying the relationship between
psychosocial stress and hypertension are various and
complex. Among them, behavioral response and patho-
physiological response are considered to play pivotal
roles. Maladaptive behavioral response consists of
smoking, alcohol consumption, inactivity, and poor
diet, and are often thought to lead to hypertension over
time. On the other hand, pathophysiological response
is mediated by physiological pathways, including the
hypothalamus-pituitary-adrenal (HPA) axis, sym-
pathetic activation, vagal withdraw, and immune
response.
The initial step in the HPA axis is the release of corti-
cotropin-releasing factor (CRF) from the paraventricular
nucleus of the hypothalamus. Binding of CRF to recep-
tors in the pituitary subsequently induces the release of
adrenocorticotropic hormone (ACTH) into the systemic
circulation. The principal target for circulating ACTH
is the adrenal cortex, where it stimulates glucocorticoid
synthesis and release. Glucocorticoid, ultimately, con-
tributes to the development of hypertension. The sympa-
thetic nervous system most likely plays a crucial role in
the pathophysio-response of the hypertension associated

with stress, which has been reviewed most recently by
Lambert et al. and by others [36–38].
More interesting is the concept of vagal withdraw.
Increasing evidence shows that changes in vagal tone
may be as important to psychosocial-induced blood
pressure increases as are sympathetic nerves and the HPA
systems [39]. Jagmeet et al. found that decreased vagal
tone is an independent predictor of new-onset hyper-
tension [40]. Because of the parasympathetic system’s
role in recovery and restoration, those who were under
chronic stress and could not relax were more likely to
develop premature coronary events [41]. These studies,
taken together, provide strong evidence that individu-
als with genetic predispositions, including hyperactive
HPA and sympathetic system and decreased vagal tone,
combined with chronic stress can lead to hypertension.
Recently, the effect of the immune system has been
implicated as a possible intermediary between psycho-
social stress and hypertension. At the center of this
pathway is angiotensin II [42–45]. Several studies have
shown chronic stress increases the circulating levels of
angiotensin II, as well as AT1 receptors in several brain
regions involved in emotional stress responses like the
amygdala [46]. Circulating angiotensin II bind angio-
tensin type 1 receptors, subsequently activating hypo-
thalamic neurons, leading to long-term activation of
the sympathetic system. This pathway has been eluci-
dated and validated both in animal and human studies
[47–50]. Furthermore, there is evidence to suggest the
CNS also activates the immune system. The spleen and
lymph nodes are innervated by the sympathetic nerv-
ous system and immune cells have adrenergic recep-
tors. Paton et al. showed that inflammatory cells and
cytokines are increased in the brain in animal hyper-
tension models and these inflammatory cells impair
central autonomic control of blood pressure regulation
[51]. In animal models, inhibition of brain AT1 receptor
activity with systemically administered Angiotensin II
receptor blockers reduced stress responses and anxiety,
and prevented stress-induced increase in cardiac events
and stroke [42]. Knockdown of the AT1 receptor in the
organum vasculosum laminae terminalis (OVLT) and
subfornical organ (SFO) regions of the brain attenuated
increase in blood pressure to stress in animal models
[52]. This data demonstrates the important role angio-
tensin II plays in stress-related hypertension.
Most recently, several studies have shown that IL-6
may also play a pivotal role in the association between
psychosocial stress and hypertension. Low socioeconomic
status, racism, and job strain – sources of chronic stress
– are associated with increased circulating levels of IL-6
[53–56]. In animal studies, knockdown of IL-6 attenuated
blood pressure increases when exposed to psychological
stress [57]. Furthermore, a clinical study measuring the
biochemical responses to laboratory stressors found that
stress-induced IL-6 elevation predicted the ambulatory
blood pressure measured three years later [58].
NEUROLOGICAL RESEARCH   575
Acute stress induces short-lasting rises in arterial
pressure and heart rate, impairs endothelial function,
and reduces the threshold for arrhythmias. However, it
is unclear whether acute stress results in sustained ele-
vation of blood pressure and hypertension [17,59]. The
association between chronic stress and hypertension, on
the other hand, is well established [60–62].
Methods
Search strategy, data extraction, and eligibility
criteria
We methodically searched the PubMed, Cochrane
Library, China National Knowledge Infrastructure
(CNKI), VIP China Science, and Wanfang databases
for the following search keywords: ‘psychosocial stress,’
‘life stress,’ ‘mental suffering,’ ‘anguish,’ ‘emotional stress,’
‘compassion fatigue,’ ‘work stress,’ ‘anxiety,’ ‘nervousness’
or ‘depression’ and ‘high blood pressure’ or ‘hyperten-
sion.’ The hyponym of ‘psychosocial stress, work stress,
anxiety, depression, hypertension’ were also retrieved.
Keyword searches were limited to English and Chinese
only. Data collection was completed by April 2016.
References of articles found with the initial search and
relevant reviews were further searched to find additional
eligible studies. The principal investigators of the stud-
ies were contacted to clarify published and unpublished
data when acquired.
The relevant articles were selected and evaluated
independently by two experienced investigators with
the following criteria: (1) assess stress using standard-
ized mental stress tests (e.g. The Trier Inventory for
the Assessment of Chronic Stress Screening Scale),
(2) utilize accepted methods to assess hypertension,
(3) evaluate the association between hypertension and
psychosocial stress, (4) design as a case-control study
or a cohort study, (5) provide sufficient information to
calculate odds ratio (OR), and (6) accessibility of the
complete text.
Appraisal of the quality of studies
All the included articles were reviewed in detail.
Research information was independently extracted
by two experienced investigators to reduce bias.
Discrepancies were resolved by discussion to reach a
consensus. When two or more articles used the same
original population data, only the article with the larger
sample size was included in this meta-­analysis. The
Newcastle Ottawa Quality Assessment Scale 24 was
used to assess article quality [63]. It has three parts:
selection, comparability, and exposure, with eight
items. The combined score ranges from zero to nine
stars. We assessed articles with seven to nine stars as
high quality, five to six stars as medium quality, and
zero to four stars as poor quality. Articles with poor
quality were excluded.
576   M.-Y. LIU ET AL.

Table 1. General information on and quality assessment of the 10 studies included in the meta-analysis.
Study (year) Study period Country Influence factor Diagnosis (hypertension/mental stress)
Ginty AT (2013) [28] 2002–2004 Netherland Hypertension Diagnosis by physician/Hospital Anxiety and Depression Scale (HADS)
Radi S (2005) [60] 1997–1998 France Hypertension Self-reported/The self-administrated questionnaire of Karasek5
Almas A (2014) [67] 2010/4–2011/3 Pakistan Hypertension Diagnosis by physician/Hospital Anxiety and Depression Scale (HADS)
Xu HH (2001) [69] 1998/1–1998/12 China Hypertension Diagnostic criteria of WHO/Eysenck Personality Questionnaire (EPQ)
Perez LH (2001) [70] 1993,1994 Columbia Hypertension SBP≥140 mm Hg or DBP ≥140 mm Hg or with antihypertensive
treatment/tension-anxiety scale
Hong YF (2014) [71] – China Hypertension Diagnosis by physician/SAS and SDS
Schutte AE (2015) [72] 2005/1–2005/12 South Africa Hypertension ≥140/90 mm Hg/Kessler Screening Scale for Psychological Distress
[K6]
Chen YH (2013) [73] 2009/1–2010/12 China Hypertension China Guideline for the Prevention and Treatment of Hypertension/
self-designed questionnaire
Meyer CM (2004) [74] 1981,1982,1993 East Baltimore Hypertension Self-reported/Diagnostic and Statistical Manual (DSM) III
Hayden B (2003) [13] – U.S.A. Depression Self-reported/Duke Depression Evaluation Schedule
Clays E (2007) [68] 2002–2003 Belgium Job strain Self-measurement/Job Content Questionnaire

Outcome Sample size(cases/noncases) Age Quality

Anxiety/depression 219/236 ≈58 High
Job constraints 61/114 41.8 ± 7.8 (man)/ High
43.5 ± 7.5 (woman)
Anxiety/depression 323/267 ≥18 High
Psychological distress 72/72 – Medium
Anxiety or tension 228/228 ≥15 High
Anxiety/depression 950/970 ≥40 High
Psychological distress 25/82 35–75 High
Work stress 89/89 18–40 Medium
Depression 148/901 ≥18 High
Hypertension 293/151 ≥58 High
Hypertension 89/89 40–64 High

Statistical analysis Search results n=5777

Data were assembled and analyzed using Review
Duplicates excluded (n=415)
Manager (RevMan) Version 5.3 (The Nordic Cochrane
Center, Copenhagen, Denmark). Odds ratio was used Articles screened according
to measure effect size with 95% confidence (95% to titles n=5362
CI). Heterogeneity was evaluated with the I2 statistic:
Excluded (n=5080)
I2 = 0–50% (insignificant to moderate heterogeneity), I2
more than 50% is considered substantial statistical heter- Articles screened based on
abstract (n=282) Excluded (n=266):
ogeneity. A random-effects model was used for calculat-
ing pooled effect size. Otherwise, the fixed-effects model Not related with mental stress or
hypertension (n=65)
was utilized. Due to discrepancies in the measurement
Not case-control or cohort studies
of mental stress across the studies, stratified analyses (n=137)
Full-text reviewed (n=16)
were performed in terms of stress types and methods of Review n=64 ;
assessing stress. Discrepancies in assessing mental stress
Excluded (n=5):
existed in different studies, but decreased markedly after
Low quality (n=2)
stratified analysis (Table 1). In addition, sensitive anal-
Incomplete data(n=3)
yses were performed by excluding studies one by one. Finally included (n=11)
Funnel plots were used to detect publication bias.
Figure 1. Flow diagram of literature search and study selection.
Results
Literature retrieval association between depression/anxiety and hyperten-
sion, two studies reported an association between psy-
In total, 5362 items from the literature were found after
chosocial distress and hypertension, and the other three
removing duplicates and reviews. After reading titles and
studies reported a relationship between work strain and
abstracts, 5080 articles were excluded. From the remain-
hypertension. Of the 11 studies, nine studies measured
ing 282 papers, 11 articles were considered for inclusion
mental stress as the primary outcome (two psycholog-
in our study after reviewing the full text (Figure 1).
ical distress, five depression/anxiety, two work stress)
while the other two studies measured hypertension
Study characteristics as the primary outcome. The eligible studies included
A total of 5696 participants were recruited in the 11 eli- cohorts spread across four continents, including Europe,
gible studies. Among the 11, six studies concluded an America, Asia, and Africa. Psychosocial stress-relevant
 NEUROLOGICAL RESEARCH   577

Figure 2. Forest plot of associations between mental stress and hypertension (OR and 95% CI indicate odds ratio and 95% confidence
internal).

Figure 3. Forest plot of associations between hypertension and mental stress (OR and 95% CI indicate odds ratio and 95% confidence
internal).

variables involved in the studies included work stress,

anxiety, depression, and life stress (Table 1).

Psychosocial stress and hypertension

The two studies using hypertension as the out-
comes showed that mental stress was associated with
an increased risk of hypertension (OR  =  2.40, 95%
CI  =  1.65–3.49, p  <  0.001), without heterogeneity
(I2 = 0%, p = 0.33). The other nine studies using mental
stress as outcomes showed that hypertension patients
had a higher incidence of mental stress than normoten-
sion patients (OR = 2.69, 95% CI = 2.32–3.11, p < 0.001), Figure 4. Funnel plot for publication bias in three studies on the
without heterogeneity (I2  =  0%, p  =  0.50) (Figures 2 association between mental stress and hypertension included
and  3). The funnel plot (Figures 4 and 5) showed no in the meta-analysis. Dashed lines indicate 95% confidence
asymmetry, indicating publication bias is not likely to intervals. OR = odds ratio; SE = standard error.
exist in the analysis.

chronic stress and long-term hypertension is still con-

Discussion
The influence of psychosocial stress on the human phys-
iology is a novel area of research. While the transient
decrease in immune response system with acute psy-
chosocial stress is well studied, the relationship between
troversial. Because hypertension is a fundamental risk
factor for cardiovascular, neurovascular, and renal dis-
eases, and places a great deal of burden on the health-
care system, the relationship between the two demands
special consideration for research [64–66].
578   M.-Y. LIU ET AL.
Figure 5.  Funnel plot of for publication bias in seven studies
on the association between hypertension and mental stress
included in the meta-analysis. Dashed lines indicate 95%
confidence intervals. OR = odds ratio; SE = standard error.
Previous studies have reported relationships between
mental stress and hypertension, but the level of evidence
varied, and the results at times contradictory. Almas et al.
reported that the relationship remained significant
even after adjusting for age and gender [67]. Clays et al.
reported that high job strain was an important inde-
pendent risk factor for higher ambulatory blood pressure
[68]. Xu et al. showed that mental stress had a higher
incidence in hypertension patients than normal indi-
viduals [69]. Conversely, the GHAIA study reported that
there was no significant relationship between psycho-
social stress and hypertension among Ghanaians [20].
Psychosocial stress promotes transient elevation in
blood pressure. Mechanistically, following the percep-
tion of an acute stress, there is cascade of changes in
the nervous, cardiovascular, endocrine, and renal sys-
tems. These changes constitute the stress response. Most
studies indicate acute stress-induced responses are short
lived and baseline is re-established shortly after the stress
is removed. However, acute stress response can become
maladaptive if it is sustained. Chronic SNS simulation
of the cardiovascular system can lead to persistent eleva-
tion in blood pressure, vascular hypertrophy, and plaque
formation. Others believe that behavior responses linked
to stress, including overeating, alcohol consumption,
and poor sleep, may augment the direct physiological
response of stress.
In this study, we found that mental stress was associ-
ated with an increased risk of hypertension (OR = 2.40,
95% CI  =  1.65–3.49, p  <  0.001). Mental stress had a
higher incidence in hypertension patients than in nor-
motension persons (OR  =  2.69, 95% CI  =  2.32–3.11,
p < 0.001). Although the meta-analysis showed a posi-
tive correlation between mental stress and hypertension,
several limitations temper the results of this meta-anal-
ysis, including a small number of studies that met our
inclusion criteria and heterogeneity between the studies
regarding to the definition of stress and the response.
Furthermore, we could not perform a stratified analysis
of the correlations between different sexes and age of
participants due to the small number of articles involved
in the review. Funnel plot did not suggest publication
bias. Shortcomings of each individual study could poten-
tially reduce the power of the study. For example, Clays
et al. relied heavily on questionnaires for job strain and
self-reported hypertension, making recall and reporting
bias a concern [68]. Nonetheless, based on our analysis,
we believe there is a robust correlation between psycho-
social stress and hypertension. However, whether psy-
chosocial stress is a risk factor for hypertension requires
further investigation.
Contributors
ML established the study’s orientation and the empha-
ses of this thesis. NL conducted literature retrieval, data
analysis, and statistical analysis. WAL and HK analyzed
data analysis and article writing.
Disclosure statement
No potential conflict of interest was reported by the authors.
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