The emotional stress and risk of ischemic stroke

Abstract

Stroke is the second leading cause of death worldwide, and the leading cause of acquired disability in adults in most regions. There have been distinguished modifiable and non-modifiable risk factors of stroke. Among them the emotional stress was presented as a risk factor. The aim of this review was to present available data regarding the influence of acute and chronic mental stress on the risk of ischemic stroke as well as discussing the potential pathomechanisms of such relationship. There is an evident association between both acute and chronic emotional stress and risk of stroke. Several potential mechanisms are discussed to be the cause. Stress can increase the cerebrovascular disease risk by modulating symphaticomimetic activity, affecting the blood pressure reactivity, cerebral endothelium, coagulation or heart rhythm. The emotional stress seems to be still underestimated risk factor in neurological practice and research. Further studies and analyses should be provided for better understanding of this complex, not fully known epidemiological problem.

Full text

Review
article
The
emotional
stress
and
risk
of
ischemic
stroke
Dariusz
Kotlęga
a,
*,
Monika
Gołąb-Janowska
a
,
Marta
Masztalewicz
a
,
Sylwester
Ciećwież
b
,
Przemysław
Nowacki
a
a
Department
of
Neurology,
Pomeranian
Medical
University
in
Szczecin,
Szczecin,
Poland
b
Department
of
Gynaecology
and
Urogynaecology,
Pomeranian
Medical
University,
Szczecin,
Poland
1.
Introduction
Stroke
is
the
second
(after
ischemic
heart
disease)
leading
cause
of
death
worldwide,
and
the
leading
cause
of
acquired
disability
in
adults
in
most
regions.
There
have
been
distinguished
modifiable
and
non-modifiable
risk
factors
of
stroke.
Among
them
the
emotional
stress
was
presented
as
a
risk
factor.
The
aim
of
this
review
was
to
present
available
data
regarding
the
influence
of
mental
stress
on
the
risk
of
ischemic
stroke
including
the
potential
pathomechanisms.
The
modifiable
risk
factors
of
stroke
account
for
88.1–
90.3%
of
the
population-attributable
risks
(PAR)
for
the
association
of
all
strokes.
The
most
important
risk
factors
of
ischemic
stroke
described
as
PAR
are
the
hypertension,
lack
of
regular
physical
activity,
ratio
of
ApoB
to
ApoA1
apolipoproteins
and
waist-to-hip
ratio.
As
presented
in
the
INTERSTROKE
multicenter
study,
the
psychosocial
factors
also
may
increase
the
risk
of
ischemic
stroke.
The
psycho-
social
stress
described
as
a
combined
measure
of
general
stress
at
home
and
in
the
workplace
(permanent
or
several
periods
of
stress
vs.
no
or
some
periods
of
stress
in
the
past
year)
was
responsible
for
ischemic
stroke
risk
increase
(OR
1.3,
99%
CI:
1.04–1.62),
PAR
value
was
calculated
as
4.7%.
Depression
defined
as
feeling
sad,
blue,
or
depressed
for
two
or
more
consecutive
weeks
during
the
past
12
months
also
modified
the
risk
(OR
1.47,
99%
CI:
1.19–1.83),
PAR
value
was
6.8%
[1].
n
e
u
r
o
l
o
g
i
a
i
n
e
u
r
o
c
h
i
r
u
r
g
i
a
p
o
l
s
k
a
5
0
(
2
0
1
6
)
2
6
5
–
2
7
0
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
29
December
2015
Accepted
14
March
2016
Available
online
23
March
2016
Keywords:
Risk
factor
Emotional
stress
Cerebral
stroke
a
b
s
t
r
a
c
t
Stroke
is
the
second
leading
cause
of
death
worldwide,
and
the
leading
cause
of
acquired
disability
in
adults
in
most
regions.
There
have
been
distinguished
modifiable
and
non-
modifiable
risk
factors
of
stroke.
Among
them
the
emotional
stress
was
presented
as
a
risk
factor.
The
aim
of
this
review
was
to
present
available
data
regarding
the
influence
of
acute
and
chronic
mental
stress
on
the
risk
of
ischemic
stroke
as
well
as
discussing
the
potential
pathomechanisms
of
such
relationship.
There
is
an
evident
association
between
both
acute
and
chronic
emotional
stress
and
risk
of
stroke.
Several
potential
mechanisms
are
discussed
to
be
the
cause.
Stress
can
increase
the
cerebrovascular
disease
risk
by
modulating
sym-
phaticomimetic
activity,
affecting
the
blood
pressure
reactivity,
cerebral
endothelium,
coagulation
or
heart
rhythm.
The
emotional
stress
seems
to
be
still
underestimated
risk
factor
in
neurological
practice
and
research.
Further
studies
and
analyses
should
be
provid-
ed
for
better
understanding
of
this
complex,
not
fully
known
epidemiological
problem.
#
2016
Polish
Neurological
Society.
Published
by
Elsevier
Sp.
z
o.o.
All
rights
reserved.
*
Corresponding
author
at:
Department
of
Neurology,
Pomeranian
Medical
University,
Unii
Lubelskiej
1,
71-252
Szczecin,
Poland.
Tel.:
+48
914253251;
fax:
+48
914253260.
E-mail
address:
dkotlega@poczta.onet.pl
(D.
Kotlęga).
Available
online
at
www.sciencedirect.com
ScienceDirect
journal
homepage:
http://www.elsevier.com/locate/pjnns
http://dx.doi.org/10.1016/j.pjnns.2016.03.006
0028-3843/#
2016
Polish
Neurological
Society.
Published
by
Elsevier
Sp.
z
o.o.
All
rights
reserved.

2.
Chronic
emotional
stress
First
report
of
chronic
psychological
stress
affecting
the
risk
of
ischemic
stroke
was
revealed
in
a
year
1990,
where
during
11.8
years
of
follow-up
in
9998
men
the
grade
of
psychological
stress
in
the
last
5
years
increased
the
risk
of
stroke
(OR
2.0,
95%
CI:
1.3–3.2,
adjusted
for
significant
risk
factors
only)
[2].
The
protocol
of
this
report
included
the
5-years-lasting
period
of
experienced
stress
(never
or
permanent)
with
definition
of
stress
as
a
feeling
of
tension,
anxiety
and
irritability.
The
answers
were
marked
in
a
postal
questionnaire
by
participants
that
might
have
led
to
not
fully
objective
conclusions.
The
association
between
self-reported
stress
frequency
and
intensity
and
risk
of
stroke
was
evaluated
in
a
13
years-
lasting
follow-up
of
12,574
patients.
Subjects
with
high
stress
intensity
had
almost
a
doubled
risk
of
fatal
stroke
compared
with
subjects
who
were
not
stressed
(relative
risk
1.89,
95%
CI:
1.11–3.21).
Weekly
stress
was
associated
with
an
RR
of
1.49
(95%
CI:
1.00–2.23).
There
was
no
significant
effect
of
stress
in
analyses
of
nonfatal
strokes
[3].
The
definition
of
stress
was
partially
different
from
the
latter,
i.e.
tension,
impatience,
anxiety,
sleeplessness.
The
presence
of
chronic
stress
in
a
8.5-
years
follow-up
was
not
related
to
increased
risk
of
ischemic
stroke,
but
a
relationship
was
observed
when
highest-scoring
group
was
compared
to
a
lowest-scoring
one
(HR
1.59,
95%
CI:
1.11–2.27)
[4].
Another
cohort
study
of
93,676
postmenopausal
women
in
a
follow-up
to
18
years
analyzed
the
score
of
stressful
life
events
and
their
impact
on
the
mood,
additionally
the
social
strain
was
evaluated
as
the
measure
of
negative
aspects
of
social
relationships.
The
high
social
strain
group
was
at
higher
risk
of
incident
ischemic
stroke
when
compared
to
low-risk
group
(HR
1.15,
95%
CI:
1.02–1.28).
On
the
other
hand
there
was
no
association
between
risk
of
ischemic
stroke
and
stressful
life
events
[5].
In
a
follow-up
of
6019
participants
lasting
for
16
years
it
has
been
shown
that
higher
levels
of
anxiety
symptoms
were
associated
with
higher
risk
of
stroke
(both
ischemic
and
intracerebral
hemorrhage).
Findings
suggested
a
dose–response
relation,
with
every
1
SD
increase
in
anxiety
associated
with
a
17%
increase
in
stroke
risk
when
adjusting
for
demographic
factors
[6].
The
investigation
of
only
one
factor
such
as
anxiety
indicates
on
the
mental
health
well-
being
as
the
significant
factor
in
the
stroke
pathogenesis,
but
should
be
distinguished
from
the
stress
as
a
general
term.
On
the
other
hand
anxiety
may
be
more
precisely
defined
and
compared
between
researches
with
the
use
of
neuropsycho-
logical
tests.
The
high
score
of
life
events
questionnaire
and
stressful
habits
were
connected
with
higher
risk
of
stroke
in
a
case–control
study
on
150
stroke
patients
[7].
Even
though
there
was
relatively
small
sample
size
presented
in
this
study,
it
should
be
noted
that
precise
and
clearly
described
methods
were
used
in
the
research
protocol
such
as
Holmes
&
Rahe
questionnaire
of
life
events,
recall
scale
of
type
A
behavior
(ERCTA),
Quality
of
Life
scale
(SF12)
and
general
health
questionnaire
(GHQ28).
There
is
an
association
between
psychological
distress
and
risk
of
death
due
to
cardiovascular
disease
(ischemic
heart
disease
and
cerebrovascular
disorders).
In
a
total
number
of
68,652
participants,
relative
to
those
with
no
symptoms
of
psychological
distress
at
baseline,
people
with
psychological
distress
had
an
increased
risk
of
death
from
cerebrovascular
disease
(HR
1.66,
95%
CI:
1.32–2.08)
[8].
In
a
cohort
study
of
237,879
males
the
association
of
stress
resilience
in
adoles-
cence
with
subsequent
stroke
risk
was
investigated.
Lowest
stress
resilience
compared
with
the
highest
was
associated
with
increased
stroke
risk,
producing
unadjusted
HR
of
1.54
(95%
CI:
1.40–1.70).
The
results
were
consistent
when
stroke
was
subdivided
into
fatal,
ischemic
and
hemorrhagic,
with
higher
magnitude
associations
for
fatal
rather
than
non-fatal,
and
for
hemorrhagic
rather
than
ischemic
stroke
[9].
In
a
population-based
study
conducted
on
4120
aged
65
and
older
participants
the
psychosocial
distress
was
investigated
in
relation
to
stroke
mortality
and
incident
stroke
over
6
years
of
follow-up.
Psychosocial
distress
was
an
analytically
derived
composite
measure
of
depressive
symptoms,
perceived
stress,
neuroticism,
and
life
dissatisfaction.
Adjusting
for
age,
race,
and
sex,
the
hazard
ratio
(HR)
for
each
1
SD
increase
in
distress
was
1.47
(95%
CI:
1.28–1.70)
for
stroke
mortality
and
1.18
(95%
CI:
1.07–1.30)
for
incident
stroke.
Associations
were
reduced
after
adjustment
for
stroke
risk
factors
and
remained
signifi-
cant
for
stroke
mortality
(HR
1.29,
95%
CI:
1.10–1.52)
but
not
for
incident
stroke
(HR
1.09;
95%
CI:
0.98–1.21).
Secondary
analyses
of
stroke
subtypes
showed
that
distress
was
strongly
related
only
to
incident
hemorrhagic
strokes,
but
not
ischemic
strokes
in
fully
adjusted
models
[10].
The
variability
of
results
in
the
sub-types
of
strokes
may
result
from
different
pathogenetic
background
in
the
particular
types
of
cerebrovascular
epi-
sodes,
thus
we
concentrate
on
the
ischemic
stroke.
In
the
preceding
year
before
stroke
only
the
long-term
severely
threatening
events
were
more
often
in
113
stroke
patients
compared
to
controls
(26%
vs.
13%,
OR
2.3,
95%
CI
1.1–4.9).
Non-
threatening
events,
events
with
only
a
short-term
threat
and
difficulties
were
not
increasing
the
risk
of
stroke
[11].
Not
only
the
stress
assessed
in
a
longer
period,
but
also
the
neighborhood
may
affect
the
risk
of
stroke
as
shown
in
a
study
of
5789
participants.
Neighborhood-level
social
cohesion
measured
by
using
the
self-assessment
protocol
describing
the
selected
aspects
of
neighborhood
interactions.
A
higher
score
of
calculated
cohesion
level
was
an
independent
factor
reducing
the
stroke
mortality.
Each
point
of
this
calculated
score
was
responsible
for
53%
reduction
of
stroke
mortality
(HR
0.47,
95%
CI:
0.26–0.86).
On
the
other
hand
there
was
no
such
an
effect
in
relation
to
stroke
incidence
[12].
The
socioeconomic
status
affects
the
risk
of
ischemic
stroke
by
increasing
the
risk
of
incident
ischemic
stroke
in
the
most
disadvantaged
neighborhoods
among
whites,
but
not
among
blacks
[13].
There
are
also
differences
in
stroke
mortality
rates
depending
on
the
level
of
poverty,
education,
population
density,
population
mobility
and
race/ethnicity
pattern
[14].
Such
observations
may
be
connected
with
stress,
but
what
is
more
likely
–
with
the
lifestyle,
medication
use
and
access
to
healthcare
providers.
This
example
indicates
on
a
complex
impact
of
the
stress
in
the
stroke
pathogenesis
and
possibility
of
both
direct
and
indirect
impact
on
the
risk
of
stroke.
Supporting
such
a
thesis
it
may
be
mentioned
that
the
grade
of
socioeconomic
status
is
associated
with
the
major
risk
factors
of
stroke
[15].
We
presented
different
aspects
of
chronic
stress
affecting
the
risk
of
stroke.
Another
type
of
stressful
factor
is
the
workplace
environment
as
a
growing
number
of
population
n
e
u
r
o
l
o
g
i
a
i
n
e
u
r
o
c
h
i
r
u
r
g
i
a
p
o
l
s
k
a
5
0
(
2
0
1
6
)
2
6
5
–
2
7
0266

spend
long
time
at
work.
As
a
secondary
consequence
it
may
lead
to
a
burnout
syndrome
which
adds
to
a
chronic
stress
level
in
individuals.
In
a
meta-analysis
of
2023
stroke
events
investigating
the
association
between
a
job
strain
and
risk
of
ischemic
stroke,
the
psychosocial
stress
at
work
increased
the
risk
of
ischemic
stroke
(HR
1.24,
95%
CI:
1.05–1.47)
[16].
It
also
should
be
noted
that
such
an
aspect
of
chronic
stress
has
presumably
huge
impact
on
everyday
level
of
stress.
If
concerned
to
a
general
level
of
stress,
presented
result
might
be
different.
Dependency
between
particular
chronic
stress
aspects
was
examined
in
small
number
of
studies.
Taking
into
consideration
several
aspects
of
chronic
stress
together,
such
as
the
workplace,
general
stress
and
stressful
life
events,
there
has
been
demonstrated
only
a
tendency
in
increasing
the
risk
of
ischemic
stroke
in
a
recent
meta-analysis
(HR
1.4,
95%
CI:
1.00–1.97;
p
=
0.05)
[17].
This
result
may
raise
some
doubts
as
a
definite
conclusion,
because
it
has
some
limitations.
It
is
difficult
to
compare
particular
studies
as
there
are
rarely
similar,
easily
comparable
methodological
solutions
used.
3.
Acute
emotional
stress
Presented
results
indicate
on
relation
between
chronic
stress
and
increased
risk
of
stroke,
but
there
are
also
data
regarding
the
acute
stressful
situations
and
incident
stroke.
First
observations
of
such
patients
were
presented
in
a
year
1956
[18].
There
is
a
study
where
247
ischemic
stroke
patients
were
interviewed
into
exposition
of
stressful
life
events
within
one
week
and
one
month
before
stroke
compared
to
such
periods
in
the
past.
Patients
were
exposed
to
≥1
life
events
more
often
during
the
first
month
preceding
stroke
onset
than
during
the
five
control
periods
(OR
2.96,
95%
CI:
2.19–4.00).
Over
the
four-
week
period,
97
patients
were
exposed
to
≥1
life
events.
Patients
were
exposed
to
≥1
life
events
more
often
during
the
first
week
preceding
stroke
onset
than
during
the
three
control
periods
(OR
2.10,
95%
CI:
1.40–3.17).
Such
observations
may
lead
to
a
conclusion
that
recent
life
events
exposure
is
associated
with
an
increased
risk
of
ischemic
stroke
[19].
In
a
hospital-based
observational
cross-sectional
study
including
224
ischemic
stroke
patients,
11
well-established
and
potential
trigger
factors
were
present
prior
to
stroke
onset
in
46.4%
patients
(analyzed
in
predefined
hazard
periods).
Psychological
stress
within
1
month
before
the
onset
was
the
most
common
and
was
present
in
16.5%
of
all
stroke
patients
[20].
During
the
2-h
hazard
period
as
much
as
38%
ischemic
stroke
patients
reported
potential
triggers
including
the
negative
and
positive
emotions
[21].
On
the
other
hand
in
a
case–control
study
of
37
ischemic
stroke
patients
there
was
no
connection
between
incident
ischemic
stroke
and
potentially
major
stressful
experience
within
the
past
month
[22].
In
a
study
of
24,315
ischemic
stroke
and
16,088
TIA
patients
it
was
observed
that
number
of
vascular
events
during
the
birthday
was
higher
than
the
expected
daily
number.
Multivariate
logistic
regression
showed
that
birthday
vascular
events
(stroke,
TIA,
acute
myocardial
infarction)
were
more
likely
to
occur
in
patients
with
a
history
of
hypertension
(OR
1.88,
95%
CI:
1.09–3.24)
[23].
In
opposition
to
the
chronic
stress
topic,
in
this
part
of
paper
the
methods
were
more
precisely
described,
but
still
there
may
be
difficulties
in
comparing
particular
studies
as
different
definitions
were
used.
A
lack
of
unified
methods
limits
the
statistical
and
practical
values
of
presented
studies.
That
is
why
we
discuss
potential
role
of
stress
in
the
risk
of
stroke
in
relation
to
the
pathogenetic
interactions.
4.
Potential
pathomechanisms
There
is
evident
association
between
emotional
stress
and
risk
of
stroke,
but
several
mechanisms
may
be
involved.
Stress
can
either
produce
neurovegetative
effects
that
predispose
to
psychosomatic
diseases
or
such
stress
can
directly
relate
to
an
increase
of
cerebrovascular
disease
risk
by
increasing
excessive
symphaticomimetic
activity.
Although
its
role
as
a
risk
factor
for
stroke
seems
plausible,
the
mechanism
by
which
psychosocial
stress
affects
the
vascular
system,
such
as
the
cerebral
endothelium,
coagulation,
or
heart
rhythm,
has
not
yet
been
established
[24].
The
physiological
reaction
in
response
to
stress
may
be
presented
as
a
multidirectional
reaction
including
the
activation
of
sympathetic
nervous
system,
hypothalamic–
pituitary–adrenal
axis
and
vagal
nerve
withdrawal.
These
processes
induce
hemoconcentration,
endothelial
dysfunction
and
inflammatory
state
respectively
[25].
Similarly,
the
exaggerated
sympathetic
stimulation
is
discussed
as
the
cause
of
the
fact
that
emotional
stress
can
precipitate
severe,
reversible
left
ventricular
dysfunction
in
patients
without
coronary
disease
[26].
During
acute
stress
atherosclerotic
vessels
are
characterized
by
endothelial
dysfunction
with
decreased
nitric
oxide
production,
resulting
in
loss
of
anticoagulant
and
profibrinolytic
properties
of
endothelial
cells
that
lead
to
exaggerated
hypercoagulability.
Acute
mental
stress
induces
qualitative
changes
in
several
procoagulant
molecules
such
as
fibrinogen,
factor
XII:C,
factor
VII:C,
factor
VIII:C,
von
Willebrand
factor
antigen,
platelet
activity,
thrombin–antithrombin
complex,
fibrin
D-dimer
as
well
as
profibrinolytic
tissue-type
plasminogen
activator.
The
impact
of
procoagulant
activity
is
stronger
than
profibrinolytic
resulting
in
hypercoagulation.
The
chronic
emotional
stress
and
psychiatric
disorders
in
a
similar
way
lead
to
a
hypercoagulation
by
promoting
the
procoagulant
molecules
and
reducing
the
fibrinolytic
activity.
An
important
factor
in
this
process
is
the
catecholamines
release
that
shows
multidirectional
activity.
Laboratory
results
may
also
be
modified
by
the
acute
stress,
i.e.
prothrombin
time
and
activated
partial
thromboplastin
time.
Exaggerated
hyperco-
agulability
in
the
response
to
acute
mental
stress
may
occur
in
the
presence
of
modulators
such
as:
older
age,
male
sex,
low
socioeconomic
status,
cardiovascular
disease,
chronic
psy-
chosocial
stress,
negative
affect,
perceived
threat
and
chal-
lenge
[27,28].
In
the
healthy
individuals
the
acute
stress
and
subsequent
increased
coagulation
does
not
have
to
be
harmful
for
vessels
leading
to
a
vascular
episode.
The
hypercoagulable
state
may
be
more
important
in
provoking
such
disease
in
individuals
with
previously
existing
disorders.
Such
a
patho-
mechanism
may
play
a
role
in
the
atherosclerotic
patients
with
stable
coronary
heart
disease
transformed
to
acute
coronary
syndrome
[29].
n
e
u
r
o
l
o
g
i
a
i
n
e
u
r
o
c
h
i
r
u
r
g
i
a
p
o
l
s
k
a
5
0
(
2
0
1
6
)
2
6
5
–
2
7
0
267

Similar
interaction
between
prothrombotic
condition
(inherited
or
acquired)
and
precipitating
factor
contribute
to
the
development
of
an
acute
venous
thromboembolism
[30].
These
findings
are
consistent
with
the
result
of
a
study
in
which
noted
a
lower
risk
of
a
myocardial
infarct
triggered
by
an
anger
in
patients
that
had
been
using
aspirin
before
compared
to
non-users
(relative
risk
1.4
vs.
2.9,
p
<
0.05).
Aspirin
users
were
more
prone
to
alleviate
the
initial
hypercoagulable
state
[31].
According
to
the
mentioned
observations
an
ischemic
stroke
can
be
provoked
by
an
acute
stress
in
individuals
with
previous
traditional,
in
majority
the
vascular
risk
factors.
A
special
group
of
stroke
patients
are
those
with
the
history
of
a
cancer
that
constitutes
approximately
7%
of
all
ischemic
stroke
patients.
A
previous
malignancy
increases
a
risk
of
stroke,
recurrent
stroke
and
cardiovascular
mortality.
The
acute
stress
may
trigger
an
ischemic
stroke
in
such
patients
due
to
the
present
significant
hypercoagulation
in
the
course
of
a
cancer
or
its
previous
treatment.
Such
a
relationship
has
not
been
studied
yet
[32].
Another
potential
pathomechanism
linking
the
acute
stress
and
cerebrovascular
episode
may
be
an
altering
of
the
immune
system.
In
an
experimental
study
of
bungee
jumping
it
has
been
shown
that
such
a
stressful
situation
significantly
increases
leukocyte
counts,
chemokine
interleukin-8,
proin-
flammatory
cytokine
Tumor
Necrosis
Factor-alpha
(TNF-
alpha)
with
unaltered
induction
of
the
anti-inflammatory
cytokine
Il-10
[33].
On
the
other
hand
an
increased
level
of
cortisol,
an
immunosuppressive
hormone,
is
observed
as
a
response
to
stress
[34].
There
is
also
a
report
of
interactions
between
inflammation
and
coagulation
in
response
to
an
acute
mental
stress.
The
D-dimer
reactivity
is
associated
with
fibrinogen,
Il-6
and
cortisol
induction
to
stress.
Fibrin
forma-
tion
is
related
to
the
stress-induced
activity
of
fibrinogen,
Il-6
and
activity
of
hypothalamo-pituitary-adrenal
axis
[35].
The
link
between
inflammation
measured
in
relation
to
the
C-reactive
protein
level
and
response
to
stress
is
observed
also
in
the
chronic
psychosocial
stress
as
presented
in
a
systematic
review
[36].
Silent
cerebrovascular
disease
which
is
pathogenetically
linked
to
a
hypertension
and
stroke
may
also
be
of
importance
in
this
discussion.
The
silent
cerebrovascular
disease
by
means
of
the
periventricular
white
matter
hyperintensities
(WMH)
is
commonly
observed
in
the
generally
healthy
adults.
It
was
found
in
83%
of
elderly
adults
(>65
years
old)
without
previous
stroke.
Its
role
was
proved
to
be
significant
in
the
development
of
atherosclerosis,
dementia
and
stroke.
The
severity
of
WMH
lesions
is
associated
with
the
risk
of
cognitive
decline
and
hypertension.
The
higher
values
of
the
blood
pressure
in
the
24-h
record
and
left
ventricular
hypertrophy
are
related
to
greater
severity
of
WMH
in
the
hypertensive
patients.
Moreover,
the
stress-induced
reactivity
of
blood
pressure
is
associated
with
the
presence
of
the
silent
infarcts
and
WMH
[37,38].
In
a
group
of
apparently
healthy
elderly
adults,
the
values
of
blood
pressure
including
the
additional
characteristics
such
as
the
casual,
awake
and
sleep
blood
pressure,
nocturnal
fall
and
sleep
variability
–
were
associated
with
the
enhanced
presence
of
WMH
[39].
The
variability
of
blood
pressure
in
response
to
an
acute
stress
is
reflecting
the
sympathetic
reactivity
and
may
exaggerate
the
development
of
atherosclerosis,
coronary
heart
disease,
carotid
intima-
media
complex
thickening
and
stroke
incidence.
When
compared
high
reactivity
to
low
reactivity
individuals,
the
risk
of
any
stroke
incidence
was
increased
by
72%
in
the
11
years
of
follow-up
period
(relative
risk
1.72,
95%
CI:
1.17–2.540)
and
87%
for
ischemic
stroke
only
(relative
risk
1.87,
95%
CI:
1.20–2.89)
[40].
The
carotid
intima-media
complex
thickness
(IMT)
is
used
as
a
systemic
atherosclerosis
marker
and
predicts
future
cardiovascular
episodes.
It
has
been
noted
that
mean
and
maximum
IMT
correlates
with
the
blood
pressure
reactivity
to
an
acute
mental
stress.
The
same
results
were
obtained
regarding
the
average
carotid
atherosclerotic
plaque
[41].
The
IMT
and
plaque
severity
may
be
connected
not
only
with
the
blood
pressure
reactivity,
but
also
the
heart
rhythm
reactivity
in
response
to
an
acute
stress
[42].
The
psychological
distress
could
also
result
in
arterial
endothelial
injury.
Studies
show
that
posttraumatic
stress
disorder
(PTSD)
victims
have
higher
circulating
catecholamines
and
other
sympathoadrenal-neuroendocrine
bioactive
agents
implicated
in
arterial
damage.
There
were
atrioventricular
conduction
defects
detected
more
often
in
the
PTSD
patients,
while
depression
was
associated
with
arrhythmias
[43].
Mental
stress
produces
significant
effects
on
the
electro-
physiologic
properties
of
the
heart
[44].
Atrial
fibrillation
is
an
important
pathogenic
factor
and
cause
of
stroke,
it
is
of
importance
that
the
acute
life
stress
during
30
days
before
the
occurrence
of
first
episode
of
atrial
fibrillation
was
more
often
than
compared
to
controls
[45].
In
a
long
term
follow-up
the
high
job-strain
was
related
to
increased
risk
for
AF
(HR
1.32,
95%
CI:
1.003–1.75)
[46].
Taking
into
consideration
these
observations,
both
direct
and
indirect
links
may
be
responsible
for
modulating
the
risk
of
ischemic
stroke
in
case
of
the
acute
stress.
Discussing
the
atrial
fibrillation
effect,
it
may
lead
to
stroke
and
acute
stress
may
only
be
the
trigger
factor
as
mentioned
above
or
part
of
the
multidirectional
effect
of
several
risk
factors.
It
would
be
of
interest
to
investigate
particular
factors
independently.
It
is
not
clear
whether
there
is
the
separate
impact
of
particular
aspects
of
mental
stress
on
the
risk
of
stroke.
This
statement
concerns
both
chronic
and
acute
stress.
On
the
other
hand
it
is
very
likely
that
complex
interaction
plays
role
in
the
stroke
pathogenesis
between
most
of
the
presented
neuropsycho-
logical
aspects.
Presumably,
common
background
such
as
personality,
childhood
and
attitude
to
chronic
stress
also
predispose
to
the
harmful
effect
of
an
acute
stress.
5.
Conclusions
The
emotional
stress,
both
acute
and
chronic
are
not
often
discussed
risk
factors
of
ischemic
stroke.
In
this
review
we
described
the
present
state
of
knowledge
within
this
field
and
potential
pathogenetic
background.
Both
acute
and
chronic
stress
is
significant
and
multidirectionaly
connected
with
the
risk
of
ischemic
stroke.
This
risk
factor
seems
to
be
still
underestimated
in
neurological
practice
and
research.
On
the
other
hand
there
is
also
a
possibility
that
stress
is
over-
estimated
risk
factor
of
stroke
as
there
have
not
been
demonstrated
in
a
satisfactory
extent
consistent,
clear
tools
for
precise,
objective
measurements
and
validated
methods.
n
e
u
r
o
l
o
g
i
a
i
n
e
u
r
o
c
h
i
r
u
r
g
i
a
p
o
l
s
k
a
5
0
(
2
0
1
6
)
2
6
5
–
2
7
0268

Further
studies
and
analyses
should
be
provided
for
better
understanding
of
this
complex,
not
fully
known
epidemiologi-
cal
problem.
Unified
examination
methods
and
definitions
are
suggested
for
the
future
studies.
Conflict
of
interest
None
declared.
Acknowledgement
and
financial
support
None
declared.
Ethics
The
work
described
in
this
article
has
been
carried
out
in
accordance
with
The
Code
of
Ethics
of
the
World
Medical
Association
(Declaration
of
Helsinki)
for
experiments
involv-
ing
humans;
Uniform
Requirements
for
manuscripts
submit-
ted
to
Biomedical
journals.
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e
f
e
r
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