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443
Changes
in
Blood
Pressure
Reactivity
and
24-Hour
Blood
Pressure
Profile
Occurring
at
Puberty
P.
A.
Modesti,
M.D.,
Ph.D.
I.
Pela,
M.D.
I.
Cecioni,
M.D.
G.
F.
Gensini,
M.D.
G.
G.
Neri
Serneri,
M.D.
and
G.
Bartolozzi,
M.D.
FLORENCE,
ITALY
From
the
Clinica
Medica
I
and
*Clinica
Pediatrica
I,
University
of
Florence,
Florence,
Italy.
ABSTRACT
To
evaluate
blood
pressure
reactivity
in
children
and
its
changes
in
adolescents,
the
acute
pressor
response
to
a
video-game
stress
test
and
the
noninvasive
ambulatory
blood
pressure
monitoring
were
evaluated
in
62
healthy
children
divided
into
three
age
groups.
Basal
blood
pressure
values
were
measured
according
to
the
NIH
Task
Force.
With
baseline
measures
and
body
mass
index
controlled
for,
analysis
of
covariance
showed
that
the
video
game
provoked
significant
and
incremental
cardiovascular
reac-
tivity
across
the
games
in
adolescents
when
compared
with
the
two
other
groups
of
children.
The
same
group
of
children
showed
also
a
significantly
higher
systolic
ambu-
latory
pressure
during
the
daytime,
whereas
no
significant
difference
was
observed
by
basal
BP
measurement.
In
conclusion
an
increased
reactivity
to
external
stimuli
was
observed
in
adolescents,
and
this
pattern
was
strictly
associated
with
a
higher
daily
blood
pressure.
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444
Introduction
Basal
blood
pressure
(BP)
progressively
rises
with
age,
and
this
increment
is
particularly
steep
during
the
early
years
of
life.l4
Moreover,
the
difference
in
blood
pressure
between
the
day
and
the
nighttime
increases
with
age.
This
dif-
ference,
which
is
very
small
in
children,5
be-
comes
remarkable
in
adulthood
when
a
circadi-
an
blood
pressure
rhythm
is
detectable
by
am-
bulatory
monitoring.
In
adulthood
the
external
stimuli
have
been
shown
to
influence
the
daily
pattern
of
BP,6
but
in
children
the
relevance
of
this
pattern
is
still
un-
clear.
In
particular,
at
adolescence,
children
un-
dergo
several
physical
and
psychological
changes
that
could
result
in
changes
in
BP
reactivity.
The
aim
of
the
present
work
was
to
investi-
gate
the
BP
changes
occurring
at
adolescence
and
in
particular
the
relationship
between
BP
reactiv-
ity
and
ambulatory
monitoring
BP
pattern.
Methods
Subjects
Investigated
Sixty-two
healthy
children,
aged
five
to
sixteen
years,
were
investigated
(Table
I).
All
the
children
investigated
were
randomly
selected
among
out-
patients
previously
examined
for
minor
diseases
at
our
outpatients
clinic.
Children
were
grouped
into
three
age
groups:
five
to
eight
years
(n
= 19),
nine
to
twelve
(n = 22),
and
thirteen
to
sixteen
(n = 21).
All
children
belonging
to
the
first
and
the
second
group
were
in
prepubertal
stage.
Children
belonging
to
the
third
group
were
all
in
postpubertal
stage.
No
subject
had
a
positive
fa-
milial
history
of
diabetes
or
hypertension.
Informed
consent
was
given
by
both
the
children
and
their
parents.
Quetelet
index
(QI
=
[weight/height2]
x 105)
and
the
Children
Body
Mass
Index’’
(CBMI
=
log
weight -
[0.0008 x height] )
were
considered
as
covariates
for
statistical
calculations.
Basal
BP
values
were
measured
by
a
standard
mercury
sphygmomanometer,
according
to
the
recom-
mendations
of the
NIH
Task
Force,4
on
at
least
three
occasions
over
a
period
of
one
month.
At
each
examination
at
least
three
measurements
were
taken
and
averaged.
The
children
underwent
a
twenty-four-hour
noninvasive
BP
monitoring
and
a
mental
stress
test
on
two
different
days.
Ambulatory
Monitoring
Ambulatory
monitoring
was
performed
by
a
portable
automatic
noninvasive
device.
At
the
beginning
and
at
the
end
of
the
twenty-four-
hour
monitoring
period
the
BP
measurements
automatically
obtained
were
compared
with
those
simultaneously
checked
by
standard
sphygmomanometer,
and
at
least
four
calibra-
Table
I
Subjects
Investigated
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445
tion
readings
were
taken
in
the
sitting
position.
Differences
of
less
than
5
mmHg
for
systolic
and
diastolic
BP
between
the
two
sets
of
readings
were
accepted
as
accurate.8
If
calibration
was
not
possible,
the
individual
was
removed
from
the
study.
The
BP
recorder
was
worn
by
the
children
for
a
twenty-four-hour
period
from
8:00
A.M.
to
8:00
A.M.
of
the
following
morning;
during
this
period
BP
measurements
were
preprogrammed
to
occur
every
fifteen
minutes.
To
prevent
arti-
factual
readings,
patients
were
requested
to
keep
their
upper
limb
as
motionless
as
possible
each
time
the
recorder
took
a
reading.
During
the
monitoring
period
all
the
subjects
attended
their
usual
activities.
They
had
breakfast
at
7:30
A.M.,
lunch
at
1:00
P.M.,
and
dinner
at
8:00
P.M.
and
went
to
sleep
at
10:00
P.M.
Systolic,
diastolic,
and
pulse
BP
lower
than
50,
30,
and
5
mmHg,
respectively,
were
arbitrar-
ily
deleted
from
each
twenty-four-hour
tracing
before
further
analysis.
Ambulatory
monitoring
was
considered
acceptable
when
less
than
8%
er-
rors
occurred;
otherwise
the
subject
was
removed
from
the
study.
For
each
subject
the
following
variables
were
obtained:
basal
measurements
recorded
at
the
be-
ginning
of
the
monitoring
period;
average
values
for
systolic
and
diastolic
ambulatory
pressure
dur-
ing
the
whole
twenty-four-hour
period;
average
systolic
and
diastolic
BP
during
the
daytime
(from
7:00
A.M.
to
10:00
P.M.)
and
during
the
nighttime
(from
10:00
P.M.
to
7:00
A.M.).
Mental
Stress
Test
A
video-game
challenge
was
administered
to
the
children
according
to
Murphy
et
a1.9
Upon
arrival
at
the
laboratory,
procedures
were
explained
to
the
child
and
parent.
Pilot
work
had
shown
that
the
instructions
were
readily
understood
by
all
children.
The
child
was
then
seated
in
the
exper-
imental
room
in
front
of
a
table
with
a
color
mon-
itor
of
a
personal
computer
and
a
game
paddle
control.
An
appropriately
sized
cuff
of
an
auto-
mated
BP
monitoring
device
was
applied
to
the
nondominant
upper
limb.
Before
starting
the
test,
the
child
was
told
to
sit
quietly
and
to
relax
so
that
the
equipment
could
be
checked.
A
baseline
period
of
ten
minutes
was
observed.
During
this
period
the
collection
of
BP
and
heart
rate
(HR)
measurements
(at
one
minute
intervals
after
the
end
of
each
pressure
check)
was
started.
The
child
was
then
asked
to
play
and
to
reach
the
best
score
he
could.
During
the
game
the
audio
volume
was
consistent
and
rather
loud
to
increase
the
child’s
involvement.
After
eight
min-
utes
the
monitor
was
turned
off
and
the
child
was
asked
to
relax
again
for
six
minutes.
After
this
recovery
period
the
child
was
told
to
try
harder
to
improve
his
score
in
an
addi-
tional
play.
The
test
was
then
repeated
for
the
same
time
period
(eight
minutes).
Then
the
child
was
asked
to
relax
again.
BP
and
HR
mon-
itoring
was
stopped
six
minutes
after
the
end
of
the
second
game.
Statistical
Analysis
Values
are
reported
as
mean
±SD.
The
BP
daily
curves
were
compared
by
multivariate
analysis
of
variance
(MANOVA) .
Average
ambulatory
pressure
values
were
compared
by
analysis
of
variance
(ANOVA)
with
Children
Body
Mass
Index
(CBMI)
and
Quetelet
Index
(QI)
as
co-
variates
to
exclude
the
effect
due
to
height
and
weight
increase.
Physiological
measurements
were
averaged
during
individual
tasks.
The
last
three
measure-
ments
during
the
postexperimental
rest
period
were
also
averaged
and
constituted
the
baseline
readings.
The
percent
BP
and
HR
increments
dur-
ing
the
test
in
the
subjects
from
the
three
groups
was
evaluated
by
analysis
of
variance
(ANOVA)
with
CBMI
and
QI
as
covariate.
Moreover,
the
curves
obtained
during
the
mental
stress
test
were
compared
by
multivariate
analysis
of
vari-
ance
(MANOVA) .
All
tests
were
performed
with
commercially
available
software.
Results
Basal
systolic
and
diastolic
pressure
and
mean
systolic
and
diastolic
pressure
readings
during
the
twenty-four
hours
for
children
belonging
to
the
five
to
eight
years
age
group
were
not
significant-
ly
different
from
those
of
children
belonging
to
the
second
group
(aged
nine
to
twelve)
(Table
II) .
The
pattern
of
the
daily
curve
of
systolic
(Figure
1)
and
diastolic
BP
(Figure
2)
of
the
first
group
was
not
statistically
different
from
that
of
the
sec-
ond
group
at
MANOVA
test
either
for
the
whole
curve
or
for
the
day
and
the
night
portions.
Children
belonging
to
the
third
group
showed
a
nonsignificant
increase
in
the
basal
systolic
and
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446
Table
II
BP
Values
Obtained
by
Basal
Measurement
and
Ambulatory
Monitoring
Day
Is
Considered
Between
7:00
A.Nr.
and
10:00
P.M.
The
Remaining
Period
(Between
10:00
P.M.
and
7:00
A.M.)
is
considered
as
Nighttime
*p
<
0.05
vs
9-12
years
group.
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447
diastolic
BP
values
when
compared
with
the
sec-
ond
group
(Table
II).
However,
their
systolic
am-
bulatory
pressure
was
significantly
different
from
that
of
the
second
group.
In
fact
the
mean
twen-
ty-four-hour
systolic
pressure
and
their
systolic
pressure
during
the
daytime
were
significantly
higher
(p
<
0.05,
for
both
values).
No
differences
were
observed
for
diastolic
values
(Table
II).
Daily
systolic
BP
curves
of
the
second
and
of
the
third
group
differed
from
each
other
during
the
daytime
between
7:00
A.M.
and
10:00
P.M.,
the
curves
of
the
oldest
children
being
significantly
higher
(p
<
0.04)
(Figure
1).
No
differences
were
observed
during
the
nighttime.
The
video-game
stress
test
induced
a
signifi-
cant
increase
of
the
systolic
blood
pressure
val-
ues
of children
aged
nine
to
twelve
in
compari-
son
with
children
aged
five
to
eight
(F = 1.98,
p
<
0.05).
However,
when
the
test
was
repeated
after
the
resting
period,
the
differences
were
no
more
observed
(F =1.53,
p = 0.16).
The
pattern
of
the
curve
obtained
during
the
first
test
in
the
third
age
group
was
slightly
but
nonsignificantly
higher
when
compared
with
the
second
group
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448
(F
= 1.70,
p
=
0.07) .
However,
during
the
second
test
the
difference
became
significant
(F
=
2.58,
p < 0.04)
(Figure 3).
The
patterns
of
diastolic
pressure
and
of
heart
rate
did
not
differ
in
the
three
age
groups.
The
analysis
of
variance
of
the
percent
incre-
ment
of
systolic
pressure
during
the
stress
test
in
the
three
groups,
with
CBMI
as
covariate,
re-
vealed
a
significant
age-related
effect
both
at
the
first
(F =
3.58,
p
<
0.027)
and
at
the
second
test
(F = 5.8,
p <
0.003).
In
particular
the
old-
est
boys
showed
a
larger
systolic
BP
increment
during
the
video-game
test
than
the
second
group
of
children
(F
=
3.56,
p
<
0.04
at
the
first
and
F
=
13.3,
p
<
0.0001
at
the
second
test
with
CBMI
as
covariate)
(Figure
4).
On
the
contrary,
no
differences
between
the
percent
systolic
in-
crement
in
the
first
and
in
the
second
group
were
found
either
in
the
first
or
in
the
second
test
(F = 2.25,
p=0.13
and
F=0.12,
p=0.88
respectively
at
the
first
and
at
the
second
test
with
CBMI
as
covariate)
(Figure
4).
No
differ-
ence
in
the
diastolic
pressure
and
heart
rate
in-
crement
was
observed
among
the
three
age
groups
(Table
III) .
Similar
results
were
obtained
when
QI
was
considered
as
covariate.
Discussion
According
to
the
present
findings,
not
only
pres-
sure
reactivity
but
also
the
persistence
of
the
ef-
fect
induced
on
blood
pressure
by
acute
external
stressful
stimuli
appear
to
be
related
to
the
age.
In
fact
in
children
in
immediately
prepubertal
stage
who
already
present
an
increased
acute
pressure
response
when
compared
with
younger
children,
this
response
gradually
extinguished
and
was
no
more
observed
at
repeated
test.
On
the
contrary,
in
adolescents,
the
increased
response
was
main-
tained.
Moreover,
ambulatory
values
recorded
during
the
daytime
rapidly
rose
in
adolescents
with
only
little
changes
of
nighttime
values.
As
a
consequence
the
height
of
the
daily
curve
became
more
pronounced.
The
psychological
stressor
employed
in
the
present
study
was
previously
shown
to
be
able
to
reliably
explore
the
acute
BP
reactivity
in
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449
Table
III
Absolute
Pressure
Values
Recorded
During
the
Stress
Test
children.7>9-11
However,
those
studies
evaluated
only
the
acute
response
to
the
stressor
stimuli
without
considering
the
persistence
of
the
effect.
Murphy
et
a19
sequentially
performed
three
video-game
tests,
but
each
game
was
considered
as
an
independent
procedure.
Harshfield
et
a1,6
who
reported
a
better
corre-
lation
of
absolute
pressure
values
recorded
during
mental
stress
than
on
physical
exercise
test
to
daytime
BP
at
ambulatory
monitoring,
failed
to
observe
any
relationship
between
the
acute
pressure
reactivity
and
the
amplitude
of
the
pressure
daily
pattern.
However,
they
defined
baseline
value
as
the
pretest
pressure
value
instead
of
the
posttest
value.
Moreover,
ambulatory
subjects
followed
their
standard
life
style
during
the
day
of
pressure
monitoring.6
On
the
contrary,
in
our
protocol,
the
challenge
was
the
same
in
the
sequential
tests,
so
that
the
results
could
be
analyzed
as
single
outcomes
with
a
repeated-measure
analysis
to
better
evaluate
the
persistence
of
higher
pressure
levels.
The
pattern
of
the
pressure
wave
response
was
similar,
but
a
persistence
of
higher
pressure
values
after
repeated
test
in
subjects
with
higher
ambulatory
waking
pressure
was
found.
The
persistence
of
increased
systolic
values
after
repeated
pressure
stimuli
could
be
relevant
in
determining
higher
ambulatory
values
observed
at
adolescence.
Large
epidemiologic
studies
showed
only
an
age-related
linear
BP
increase
from
infancy
to
adulthood4>5>12-15
with
no
significant
changes
oc-
curring
at
puberty.
The
difference
between
the
awake
and
the
sleep
pressure
is
very
small
in
the
neonatal
period
(5-7
mmHg),5
whereas
it
in-
creases
in
adults. 16
According
to
our
data
this
change
seems
to
occur
at
adolescence
when
the
BP
pattern
becomes
more
pronounced
with
only
little
difference
at
BP
recorded
at
morning.
At
pu-
berty
a
rapid
increase
in
body
weight
and
height
occur, 17,18
but
our
results
failed
to
find
any
rela-
tionship
of
ambulatory
pressure
changes
with
the
increase
in
body
mass
index.
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450
Conclusion
A
change
of
the
reactivity
to
external
stimuli,
al-
ready
evident
at
prepubertal
stage,
is
clearly
man-
ifest
in
postpubertal
children,
in
whom
the
per-
sistence
of
the
pressure
effect
of
the
psychological
stimulus
became
evident,
and
those
changes
in
BP
reactivity
could
be
responsible
for
the
changes
in
BP
daily
pattern.
P.
A.
Modesti,
M.D.,
Ph.D.
Clinica
Medica
I,
University
of
Florence
Viale
Morgagni
85
50134,
Florence,
Italy
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