Contribution of Stroke Volume to the Change in Pulse
Pressure Pattern With Age
José Alfie, Gabriel D. Waisman, Carlos R. Galarza, Mario I. Cámera
Downloaded from http://hyper.ahajournals.org/ by guest on June 14, 2017
Abstract—This study investigated the effect of age on pulse pressure and its underlying mechanisms in unmedicated
hypertensive men with the same level of mean arterial pressure. We included 77 men 17 to 76 years old with daytime
mean arterial pressure between 95 and 114 mm Hg. In the supine position, pulse pressure showed a significant widening
in young (,30 years) and older ($60 years) patients. Pulse pressure decreased in parallel with stroke index from age
.30 to 40 to 49 years. Upright posture, however, eliminated this difference through a larger orthostatic fall in stroke
index and pulse pressure in the youngest patients. After age 50 years, pulse pressure exhibited a progressive widening
despite the further age-related decrease in stroke index. Supine, upright, and 24-hour pulse pressure fitted a curvilinear
correlation with age (r50.55, 0.56, and 0.68, respectively, P,0.001), with a transition at age 50 years. Before age 50
years, 24-hour pulse pressure correlated positively with stroke volume (r50.5, P,0.001) and negatively with arterial
compliance (SV/PP ratio, r520.37, P,0.01). In contrast, in men $50 years old, 24-hour pulse pressure correlated
negatively with the SV/PP ratio (r520.5; P,0.01), without significant influence of stroke volume. Thus, in
hypertensive men, the age-related change in stroke volume significantly accounted for the change in clinic and
ambulatory pulse pressure during young adulthood, but its contribution decreased after the fifth decade. (Hypertension.
1999;34[part 2]:808-812.)
Key words: age n pulse pressure n stroke volume n hypertension, arterial n blood pressure monitoring
I
ncreased pulse pressure represents a hemodynamic stimulus for cardiac and vascular hypertrophy1 and may reflect
arterial stiffness and atherosclerotic disease.2 Stiffness of
large conduit arteries impairs the capacity to buffer the
change in pulse pressure for a given stroke volume and
explains the increased pulse pressure in the elderly.3 Increased pulse pressure, however, may be also explained by a
hyperkinetic circulatory state in young patients with systolic
hypertension.4
High cardiac output characterizes the early phase of arterial
hypertension. As patients get older, however, cardiac output
gradually decreases at the expense of stroke volume.5 The
age-related decrease in stroke volume, by reducing pulse
pressure, could explain the low proportion of systolic hypertension among middle-aged hypertensive individuals.6 A
reduction in arterial compliance after the middle adult years,
however, could overcome the negative effect of the decreasing stroke volume on pulse pressure in older patients.
In addition to ventricular ejection and structural characteristics of the arterial wall, the amplitude of pulse pressure is
passively related to the level of mean arterial pressure
(MAP).7 Therefore, unless MAP is controlled at the same
level, it would not be possible to analyze the effect of age on
pulse pressure.7 Accordingly, in the present study we investigated the effect of age on conventional and ambulatory
pulse pressure and its underlying mechanisms in unmedicated
hypertensive men with the same level of MAP. Increasing age
is associated with a greater increase in clinic than ambulatory
blood pressure.8 –10 Therefore, in this study patients were
matched by the level of ambulatory MAP.
Methods
We screened 99 hypertensive men (clinic blood pressures
$140 mm Hg systolic or $90 mm Hg diastolic, or both, on 2
occasions) with body mass index (BMI) #35 kg/m2 who had no
evidence of secondary cause of hypertension or major diseases and
were free of antihypertensive medication for $2 weeks (1 month in
the case of diuretics). Patients were carefully matched according to
daytime MAP. Finally, 77 patients with daytime MAP between 95
and 114 mm Hg were selected.
Anthropometric measurements (height and weight) were made
after patients had removed their shoes and upper garments. BMI was
calculated as weight (in kilograms) divided by height (in meters
squared).
Ambulatory blood pressure was recorded in the nondominant arm
every 10 minutes between 7 AM and 11 PM and every 20 minutes
between 11 PM and 7 AM with a Spacelabs 90207 monitor. Nighttime
was defined according to the period of nighttime sleep based on the
patient’s diary. Readings of systolic blood pressure (SBP) .260 or
,70 mm Hg, diastolic blood pressure (DBP) .150 or ,40 mm Hg,
and pulse pressure .150 or ,20 mm Hg were automatically
discarded. Only studies with $90% of valid readings were included.
Patients were instructed to avoid smoking and avoid drinking tea
or coffee the morning of the hemodynamic study. Hemodynamic
Received May 10, 1999; first decision June 4, 1999; revision accepted July 19, 1999.
From the Hypertension Unit, Hospital Italiano de Buenos Aires, Argentina.
Correspondence to José Alfie, MD, Unidad de Hipertensión Arterial, Servicio de Clı́nica Médica, Hospital Italiano, Gascón 450 (1181), Buenos Aires,
Argentina. E-mail [email protected]
© 1999 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
808
Alfie et al
Stroke Volume and Pulse Pressure in Hypertension
809
Anthropometric Parameters According to Age
Age, y
,30
30 –39
40 – 49
50 –59
$60
16
17
18
10
16
Age, y
2363
3562
4663
5563
6864
Weight, kg
8369
81612
87613
78615
Height, cm
17865
17666
CS, m2
1.9960.12
1.9260.28
BMI,
kg/m2
2662
2663
Variable
n
17767
260.12
2863
7667
17267
17265*
1.860.34
1.860.24
2663
2662
CS indicates corporal surface. Values are mean6SD.
*P,0.05 by 1-way ANOVA.
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evaluations were performed immediately before or after the 24-hour
ambulatory blood pressure monitoring in most cases, or at least
within the same week. Blood pressure was determined with a
mercury sphygmomanometer on the right arm with cuffs of adequate
size. Stroke volume was estimated noninvasively by impedance
cardiography (Minnesota model 304B, Surcom Inc) by use of a
technique and formula described elsewhere.11,12 Blood pressure and
tracings of the first derivative of thoracic impedance were obtained
in duplicate after 10 minutes of supine rest and during the first 3
minutes of upright position by observers blinded to the ambulatory
blood pressure findings. Heart rate and stroke volume were calculated from tracings of consecutive cardiac cycles recorded at a paper
speed of 50 mm/s. Several reports have shown the accuracy of
impedance cardiography for estimating stroke volume and cardiac
output.13,14 In our hands, the correlation coefficient between simultaneous impedance cardiography and thermodilution determinations
of cardiac output was 0.94, and the mean paired difference was 0.08
L/min (95% CI, 20.12 to 0.27 L/min).12 The regression equation for
the 2 methods was y520.7611.17x, where y5cardiac output by
impedance cardiography and x5cardiac output by thermodilution.12
Stroke index was obtained by dividing stroke volume by meters
squared. Pulse pressure was calculated as the difference between
SBP and DBP (using the Korotkoff phase V for defining DBP). The
ratio of stroke volume to brachial pulse pressure (SV/PP) was used
as a crude measure of systemic arterial compliance.15
Figure 1. Top, Influence of age on supine and upright pulse
pressure (PP, F) and stroke index (SI, E). Bottom, Influence of
age on supine and upright SV/PP ratio. Values are mean6SD.
1P,0.05 vs first age group and *P,0.05 vs fifth age group.
Statistical Analysis
Results are expressed as mean6SD. Subjects were grouped into 5
age strata (,30, 30 to 39, 40 to 49, 50 to 59, and $60 years).
Differences among age groups were assessed by ANOVA with
Bonferroni’s t test when the ANOVA was significant. The relationships of pulse pressure and age were also evaluated by use of linear
and quadratic models. The transition in the curve of pulse pressure
and age was estimated by multiple regression analysis including a
dummy variable. Within-group differences were evaluated by paired
t test. Associations between 24-hour pulse pressure and hemodynamic variables were assessed by simple correlation coefficients.
Results
The clinical characteristics of the study subjects are shown in
the Table. Patients in the fourth and fifth age groups had a
shorter stature than those in the younger groups but comparable BMI.
Supine Pulse Pressure
As shown in Figure 1, supine stroke index decreased significantly (P,0.05 by ANOVA) between the first (,30 years)
and the fifth ($60 years) age groups, with a parallel narrowing of pulse pressure up to age 40 to 49 years (P,0.05 by
ANOVA). After age 50 years, pulse pressure showed a
progressive widening despite the further decrease in stroke
index (Figure 1). In contrast to stroke index, there were no
significant age-related differences in heart rate. The SV/PP
ratio remained constant up to the third age group, reflecting
the parallel change of stroke index and pulse pressure during
young adulthood. It fell significantly, however, after age 50
Figure 2. Relation of supine and 24-hour pulse pressure and
age (left) and upright and 24-hour pulse pressure and age
(right).
810
Hypertension
October 1999 Part II
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Figure 4. Correlation of 24-hour pulse pressure (24 hr PP) and
supine stroke volume (SV) in patients younger (top) and older
(bottom) than 50 years of age. For correlation coefficients see
text.
Figure 3. Influence of age on daytime and nighttime pulse pressure (PP, top) and MAP (bottom). Values are mean6SD.
1P,0.05 vs first age group and *P,0.05 vs fifth age group by
ANOVA and Bonferroni t test.
years, indicating the progressive dissociation between pulse
pressure and stroke index in the older decades (Figure 2).
Upright Pulse Pressure
When patients assumed an upright position (Figure 1), stroke
index and pulse pressure showed a parallel fall, but the changes
were significantly attenuated by age (1-way ANOVA, P,0.05
and ,0.001, respectively). Therefore, in the upright position,
pulse pressure became “normal” in the youngest group but
remained significantly increased in the oldest group (Figure 1).
The SV/PP ratio decreased in the vertical position (P,0.001),
indicating a greater postural fall in stroke index than the
corresponding change in pulse pressure (Figure 1).
Ambulatory Pulse Pressure
Supine, upright, and 24-hour pulse pressure fitted a curvilinear correlation with age (r50.58, 0.56, and 0.80, respectively,
P,0.001), with a transition at age 50 years for the 3
correlations. Supine pulse pressure overestimated
(8610 mm Hg, P,0.001) and upright pulse pressure underestimated (24611 mm Hg, P,0.003) the corresponding
24-hour measurement. Interindividual variation was much
greater for supine and upright pulse pressure than for 24-hour
pulse pressure (Figure 2).
The paired difference between daytime and nighttime pulse
pressure reached statistical significance but showed a considerable overlap (5068 versus 4867 mm Hg, respectively,
P,0.01). As shown in Figure 3, MAP exhibited a much
larger decrease from day to night (10565 versus
8768 mm Hg, P,0.001), with a progressive attenuation in
the older decades. The night-day ratio of pulse pressure
showed a better correlation with the night-day ratio for SBP
(r50.59, P,0.001) than with the corresponding night-day
ratio for MAP, DBP, or heart rate (r50.37, P,0.002;
r50.23, P,0.05; and r50.23, P,0.05, respectively).
The hemodynamic correlates for ambulatory pulse pressure
were assessed separately in the ,50- and $50-year-old
groups (n551 and 26, respectively). In younger men, 24-hour
pulse pressure showed positive and significant correlations
with both supine and upright stroke volume (r50.47,
P,0.002 and r50.44, P,0.002, respectively) and a negative
correlation with supine SV/PP ratio (r520.37, P,0.01). In
contrast, in men $50 years old, 24-hour pulse pressure
showed negative and significant correlations with both supine
and upright SV/PP ratio (r520.5, P,0.01 and r520.6,
P,0.002, respectively), without significant correlation with
stroke volume (Figure 4).
Discussion
The present study investigates the change in conventional and
ambulatory pulse pressure as a continuum across the adult
age range in untreated hypertensive men with the same level
of MAP. Both supine and ambulatory pulse pressure exhibited a U-shaped relation with age. Widening of pulse pressure
was associated with increased stroke volume in the young and
reduced arterial compliance in the older patients. The agerelated decrease in stroke volume resulted in a parallel
narrowing of pulse pressure up to age 50 years. A significantly larger postural fall in stroke volume in the youngest
patients, however, “normalized” the increased supine pulse
pressure observed before age 30 years.
The postural decrease in pulse pressure was smaller than
the corresponding change in stroke volume. The orthostatic
decrease in the SV/PP ratio suggests an adaptive response of
Alfie et al
Stroke Volume and Pulse Pressure in Hypertension
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conduit arteries to attenuate the effect of the postural decrease
in blood flow on pulse pressure.
Widening of pulse pressure after age 50 years was independent of the level of stroke volume. Moreover, a progressive dissociation between pulse pressure and stroke volume
was noted after that age. The reduction in arterial compliance
(indicated by the progressive decrease in the SV/PP ratio)
overcame the effect of the decreasing stroke volume on pulse
pressure, explaining the lack of correlation between stroke
volume and pulse pressure after age 50 years.
Narrowing of pulse pressure during young adulthood could
favor the change from a systolic to a diastolic pattern of
hypertension in middle-aged patients. The reciprocal change
in the proportion of systolic and diastolic forms of hypertension between 25 and 65 years observed in population studies6,16 resembles the curvilinear change in pulse pressure
reported here. In a national survey from Argentina,16 systolic
hypertension (SBP $140 and DBP ,90 mm Hg) was found
in '42% of the hypertensive population before age 25 years
and fell to ,20% between age 35 and 54 years, returning to
the initial proportion after age 65 years. A transient narrowing
of pulse pressure produced by the age-related decrease in
stroke volume could favor these changes in the pattern of
blood pressure elevation. A decrease in arterial compliance
after the middle adult years could overcome the effect of the
decreasing stroke volume.
The age-related change in SV/PP ratio in our study
resembles the findings reported by de Simone and colleagues17 in normotensive individuals. In agreement with
their results, SV/PP ratio remained relatively constant between 17 and 50 years, after which it decreased steeply.
In the present study, brachial instead of aortic pulse
pressure was used for the calculation of the SV/PP ratio. An
increase in pulse-wave velocity with aging causes a proximal
summation of the forward and backward waves, attenuating
the difference between central and peripheral pulse pressure.3
Therefore, the use of brachial instead of aortic pulse pressure
could underestimate arterial compliance in young patients.
Previous studies have found better correlations between
pulse pressure and target organ damage18 and cardiovascular
risk in hypertension19 when ambulatory rather than conventional measurements were used. The present data show that
postural differences in pulse pressure represent a source of
discrepancy between conventional and ambulatory measurements. Supine pulse pressure overestimated, and upright
pulse pressure underestimated, the corresponding ambulatory
readings. The pulse pressure value in the upright position
would be expected to be similar to that during daytime (when
patients spend most of the time in the vertical position). Sitting
or walking pulse pressure, however, could attenuate the mere
effect of upright posture on daytime pulse pressure value.
It has been well established that increasing age attenuates the nocturnal fall in SBP and DBP and heart rate20;
however, the corresponding change in pulse pressure has
been less explored. The present study shows that in
contrast to the diurnal change in MAP, there was a
considerable overlap between daytime and nighttime pulse
pressure through the adult age range. Correlation analyses
indicate that the magnitude of the nocturnal fall in pulse
811
pressure is more closely related to the nocturnal change in
SBP than to the change in DBP. Hemodynamic changes
evoked during sleep could explain the smaller nocturnal
decrease in pulse pressure compared with the MAP. The
increase in venous return and stroke volume during recumbency or the nocturnal bradycardia could maintain a wide
pulse pressure despite the passive improvement of arterial
compliance due to a lower MAP.
Calculation of daytime and nighttime pulse pressure from
SBP and DBP reported in larger studies shows comparable
findings. For example, in 1052 hypertensive men from the
PIUMA study,10 daytime and nighttime pulse pressure averaged 53 and 53 mm Hg, 49 and 46 mm Hg, 48 and
44 mm Hg, 50 and 48 mm Hg, 57 and 56 mm Hg, and 61 and
61 mm Hg from the third to the eighth decade, respectively.
Similarly, in 517 normotensive men from the Belgian Population Study,8 daytime and nighttime pulse pressure averaged
50 and 49 mm Hg between 20 and 39 years, 46 and
44 mm Hg between 40 and 59 years, and 52 and 49 mm Hg
in those $60 years old.
In conclusion, the study shows a curvilinear change of
pulse pressure with age in men with similar levels of MAP.
Before the age of 50 years, the amplitude of pulse pressure
was proportional to the changes in stroke volume. In contrast,
a progressive dissociation between stroke volume and pulse
pressure was noted after age 50 years, indicating a reduction
in arterial compliance. Ambulatory pulse pressure reproduced
the U-shaped relation with age observed with supine measurements, with a considerable overlap between daytime and
nighttime readings.
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Contribution of Stroke Volume to the Change in Pulse Pressure Pattern With Age
José Alfie, Gabriel D. Waisman, Carlos R. Galarza and Mario I. Cámera
Downloaded from http://hyper.ahajournals.org/ by guest on June 14, 2017
Hypertension. 1999;34:808-812
doi: 10.1161/01.HYP.34.4.808
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1999 American Heart Association, Inc. All rights reserved.
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