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doi: 10.1111/j.1475-097X.2007.00774.x
AstraZeneca R&D Molndal, Sahlgrenska University Hospital, Goteborg, and 2Department of Medical Sciences, University Hospital, Uppsala, Sweden
Summary
Correspondence
Catherine Ahlund, Department of Medical Sciences,
AstraZeneca, SE-431 83 Molndal, Sweden
E-mail: catherine.ahlund@astrazeneca.com
Key words
exercise; mental stress test; non-invasive blood
pressure; pressure pulse reflection; pulse contour
analysis
Objectives: Analysis of the contour of the arterial pressure pulse (pulse wave
analysis; PWA) adds information about arterial stiffness etc., beyond that
obtained from absolute pressures. Peripheral pulses normally show an anterograde systolic peak and two reflected peaks: one in systole and one in diastole.
The amplitudes and timings of these were estimated from finger pressure
recordings in three study groups. We studied the usefulness of continuous digital
pressures for PWA.
Methods: First, PWA from intra-arterial (brachial) and non-invasive finger pressure
recordings was compared. Secondly, stress-induced (mental arithmetics and cold
pressor test) changes in pressure pulse reflection were compared with blood flow
changes in brachial and femoral arteries (ultrasound). Thirdly, the influence of
age and gender on digital pulse pressures was investigated at rest and during
exercise.
Results and conclusion: Pulse wave analysis results from brachial and digital pressures
correlated strongly. Stress induced changes in systolic reflection were associated with
changes in brachial artery flow patterns, whereas diastolic reflection was associated
with femoral artery flow changes. At rest, age increased systolic reflection without
affecting diastolic reflection. Exercise increased systolic reflection and reduced
diastolic reflection more in older subjects (>40 years) than in younger (<40 years).
In conclusion, PWA from continuous, digital pressure recordings is a convenient
technique to study the arterial function at rest and during exposure to stressors in
broad populations. The two reflected waves are differently regulated, which may
indicate different anatomical origin.
Introduction
The arterial pulse represents the summation of left ventricular
outflow and reflected pressure waves from the periphery. The
waveform varies throughout the arterial tree, and especially the
aortic systolic pressure may differ markedly from peripheral
arterial systolic pressure (Pauca et al., 1992). Such differences are
important as cardiac workload is determined by aortic rather
than peripheral blood pressure, and thus cannot directly be
estimated from peripheral pressure measurements. However,
aortic pressure waveforms can be generated from peripheral
waveforms such as the radial artery waveforms obtained by
applanation tonometry by the application of a general transfer
function, and cardiac workload can be estimated by analysis of
pressure waveforms (Karamanoglu & Feneley, 1996). Increased
86
0 = Onset of systole
a = Peak systole
b = Reflected wave in systole
d = Reflected wave in diastole
d
AIx = Relative amplitude of systolic reflected wave
RIx = Relative amplitude of the first diastolic reflected wave
SRt = Time to systolic peak
At = Time to systolic reflected wave
Rt = Time to the first diastolic reflected wave
Study protocol 3
This study was performed in three separate series of experiments. The local Ethics Committee approved all the three
protocols. All subjects included gave written informed consent.
The aim was to investigate differences of pulse wave characteristics during rest (supine), and bicycle exercise due to age and
gender. Sixteen females and 17 males were included in this
protocol. They were free from cardiovascular and other serious
illnesses and free of regular medication. The subjects were
divided into groups with respect to age, younger (<40 years)
and older (>40 years) and gender. All examinations took place
in the morning after an overnight fast.
After positioning of ECG electrodes and the digital blood
pressure measurement equipment, the subject rested in supine
position for 30 min. During the last 5 min of rest, heart rate and
blood pressure were continuously recorded. These registrations
were followed by bicycle exercise. The subjects were instructed
to pedal with a rate of 60 turns per minute and the workload
was adjusted until the subjects reached a heart rate of 100 beats
per minutes, and digital pressure was recorded for 5 min after
steady state heart rate was achieved.
Study protocol 1
To investigate if PWA finger tip pressure measurements of
reflected waves produce results similar to those from invasively
measured blood pressure, pulse waves were simultaneously
recorded with a Portapres (FMS, Finapres Medical Systems BV,
Amsterdam, The Netherlands) device in a finger, and invasively
through an indwelling arterial catheter in the brachial artery in
the contra-lateral arm. Both pressure measurements were
sampled with the same frequency and analysed in the Pharmlab
software described below. This procedure was performed in 11
young healthy subjects (seven males and four females), with a
mean age of 24 years. All examinations took place in the
morning after an overnight fast.
After positioning the ECG electrodes, the digital blood
pressure measurement equipment and the arterial catheter, the
subjects rested in the supine position for 30 min. During the last
5 min of rest, heart rate and blood pressure waveforms were
continuously recorded. Coefficients of variability of the PWA
estimates were performed on eight subjects (mean age
22 years). Measurements were performed on resting subjects
at four occasions separated by at least 2 days.
Methods
Invasive pressure recordings
The intra-arterial blood pressure recordings were obtained by a
catheter (20G 110 45 mm) connected to a pressure tube
(150 mm) and a transducer (DTX Plus Transducer DT-XX,
Franklin Lakes, NJ, USA). The signals were registered by GE
Marquette Eagle4000 (Stockholm, Sweden).
Study protocol 2
The aim of this study was to investigate if changes in the two
reflected pressure waves during stressful interventions were
correlated to changes in blood flow. This study was performed
in 12 male subjects. All examinations took place in the morning
after an overnight fast.
After positioning the ECG electrodes and the digital blood
pressure measurement equipment, the subjects rested in the
supine position for 30 min. During the last 5 min of rest,
heart rate and the digital blood pressure were continuously
recorded and a Doppler examination was performed (see
below). After that baseline examination, the subjects were
subjected to two different stressors, 5 min of mental stress
(mental arithmetics, MAT) and 5 min of painful stress (the
cold pressor test, COP) during which heart rate and blood
pressure were continuously recorded and Doppler examinations were reperformed. Between these interventions, there
was at least 15 min of rest to allow haemodynamic variables
to return to baseline.
During MAT stress, the subjects were instructed to subtract 13
or 17 from a three-digit number as quickly and accurate as
possible. During this test, the subjects were intentionally
frustrated by being corrected frequently and by playing loud
unpleasant music. During the COP test, one foot was placed in
ice-cold water for 5 min.
Statistics
In study protocol 1 and 2, differences between means were
calculated by paired t-test, and relationships between variables
were evaluated by linear regression analysis. In protocol 3,
effects of age, gender and exercise were analysed by two-way
ANOVA. P<005 was regarded as significant.
Results
Study protocol 1
Results obtained are shown in Table 1. Digital SBP and DBP
were lower than those obtained invasively. Systolic reflection
index (AIx; P<00001) and diastolic reflection index (RIx; P =
00009) were also lower when measured in the finger. Systolic
rise time (SRt, P<00001) and time to the Rt (P = 0001)
were both shorter when measured in the finger than in the
brachial artery. The time from the onset of systole to the At
(P = 0520 ns) did not differ between the two methods.
Importantly, all pulse wave characteristics were significantly
correlated when the intra-arterial and digital registrations were
compared (Table 1). When PWA was analysed at four
different occasions to investigate the reproducibility of the
method the CV for AIx was 16%, RIx 10%, At 6% and 4%
for Rt.
Brachial artery
Femoral artery
III
II
IV
III
II
50
114
64
063
056
134
274
487
(8)
(11)
(6)
(008)
(007)
(12)
(16)
(22)
Non-invasive
49
107
56
049
049
121
271
478
(7)
(10)
(8)
(010)
(007)
(10)
(20)
(20)
P-value
012
0015
00032
<00001
00009
<00001
051
00011
098
074
057
070
075
084
075
094
HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure and pulse wave characteristics (see Fig. 1 for definitions) obtained
through invasive measurements in the brachial artery and non-invasive
measurements in the finger.
Mean and SD (in brackets) are shown. Statistical analysis showed significant differences in all measures except HR and At. However, there
was a strong correlation between all pressure contour derived measures.
Abbreviations as in Fig. 1.
Study protocol 2
Table 2 shows that SBP and DBP were increased by the stressful
interventions, with the most pronounced increase during COP.
Also HR differed significantly between the studied periods, with
the most pronounced increase seen during MAT. Both AIx and
RIx were significantly changed by the interventions. AIx was
mainly increased during COP, but also increased slightly during
MAT. RIx was reduced during MAT only. Also At and Rt were
significantly changed by the interventions. At was reduced more
during MAT than COP, Rt was reduced during MAT only.
There were positive associations between changes in flow and
pressure waves obtained during MAT and COP. Brachial artery
FV1 phase III to phase I ratio were significantly increased by
both interventions, the increase was larger for COP than MAT
Baseline
SBP (mmHg)
DBP (mmHg)
HR(bpm)
AIx
RIx
At (ms)
Rt (ms)
Brachial phase III I ratio
Brachial phase III I (ms)
Femoral phase II I ratio
Femoral Phase II I (ms)
120
60
64
044
042
246
422
018
218
041
197
Mental stress
(13)
(12)
(7)
(011)
(005)
(16)
(15)
(015)
(61)
(012)
(15)
135
74
85
047
036
223
399
027
190
027
170
(15)
(11)
(14)
(010)
(007)
(21)
(19)
(017)
(61)
(012)
(19)
(as the changes in AIx). Also the time between the phase I and
phase III FV1 peaks changed significantly during the interventions. Similar reductions in this time index were seen during
both MAT and COP.
Femoral artery FV1 phase II to phase I ratio was significantly
changed by the interventions. This ratio was mainly reduced
during MAT. Also the time between the phase I and phase II FV1
peaks changed significantly during the interventions, with the
most pronounced reduction seen during MAT. This pattern was
the same as that for RIx and Rt (Table 2). Thus, changes in
brachial artery flow in phase III were associated to changes in
systolic reflection, and the magnitude of flow reversal in the
femoral arteries was associated to diastolic reflection.
Study protocol 3
Resting conditions
Baseline characteristics of the subjects are shown in Table 3. The
males had higher blood pressure than females, but no significant
effect on blood pressure by age was found. Heart rate did not
differ between the groups.
Results from PWA at rest are shown in Table 3 and Figs 3 and
4. There was a significant positive correlation between AIx and
age (P<00001), while there was no significant effect of age on
the RIx. SRt increased significantly with age (P = 00003), while
on the contrary the time to the At decreased (P = 0002). There
were no significant interactions between age and gender
regarding these indices of PWA. Time from onset of systole to
the Rt, did not vary significantly with age. Females tended to
have higher AIx than males, although the difference was not
significant (P = 011). Also At tended to be shorter in male
subjects (P = 007), but Rt was not affected by gender.
During exercise, both diastolic (P = 00004) and systolic
blood pressure (P = 00003) were significantly higher in males
(Table 3). SBP was significantly higher in the older groups
Cold pressor
148
84
68
064
041
241
413
031
188
035
184
(15)
(11)
(13)
(015)
(007)
(22)
(19)
(012)
(59)
(012)
(21)
ANOVA
00001
00001
00001
00001
0003
00001
00001
0002
003
00006
00002
PWA from digital pressure and brachial and femoral artery blood flow pulses during rest, mental
arithmetics and cold pressor tests. Mean values and SD (in brackets) are shown. All variables were
significantly affected by the stressors. Significant correlations were obtained between changes in
systolic reflection (AIx and At) and changes in brachial artery phase IIII measures, and between
changes in diastolic reflection (RIx and Rt) and changes in femoral artery phase II-I measures.
Abbreviations as in Figs 1 and 2.
2007 The Authors
Journal compilation 2007 Blackwell Publishing Ltd Clinical Physiology and Functional Imaging 28, 2, 8695
Table 3 PWA of finger pressures from older and younger males and females.
Female, younger
Age (years)
Height (cm)
Weight (kg)
HR (bpm) rest
SBP (mmHg) rest
DBP (mmHg) rest
SBP (mmHg) exercise
DBP (mmHg) exercise
SRt (ms) rest
SRt (ms) exercise
24
170
65
52
102
53
151
66
116
87
(3)
(7)
(10)
(7)
(8)
(5)
(18)
(10)
(8)
(7)
Female, older
53
164
60
54
97
52
174
70
138
95
Male, younger
(8)
(5)
(8)
(4)
(8)
(6)
(14)
(4)
(14)
(4)
25
182
72
53
111
60
180
79
123
89
Male, older
(4)
(6)
(10)
(7)
(14)
(6)
(20)
(11)
(13)
(8)
54
185
83
55
116
63
199
83
136
95
(8)
(8)
(13)
(9)
(17)
(8)
(17)
(11)
(12)
(8)
Age
Gender
Interaction
06859
04846
04408
09058
06092
00071
02489
00003
00054
<00001
00009
06421
00024
00002
00003
00004
05709
05689
01000
00414
08726
02902
03916
06821
09990
02831
06131
Blood pressure, SRt and descriptive charachteristics of the younger and older subjects studied at rest and during exercise. Mean values and SD (in
brackets) are shown. Statistical analysis showed that blood pressure was higher in males than in females both at rest and during exercise. Systolic blood
pressure during exercise was higher in the older groups. Systolic rise time was longer in the older subjects.
Reflectance index
Augmentation index
Rest
Exercise
Rest
Exercise
09
08
07
06
05
04
03
02
Female older
Male older
Male younger
Female younger
Female older
Male older
Male younger
Female younger
Female older
Male older
Male younger
Female younger
Female older
Male older
Male younger
01
Female younger
Discussion
In this study, we provide further evidence for PWA from
continuous digital blood pressure measurements as a simple and
non-invasive technique to investigate arterial properties. First,
there was a direct and quantitative relationship between results
from PWA performed on recordings from invasive brachial
artery recordings and finger pressure measurements. Secondly,
support for different origins for the major reflected waves was
obtained by linking brachial and femoral artery blood flow
patterns to results from PWA. Thirdly, by extending previous
Rt
At
Rest
Rest
Exercise
Exercise
500
*
Time (ms)
400
*
300
200
Female older
Male older
Male younger
Female younger
Female older
Male older
Male younger
Female younger
Female older
Male older
Male younger
Female younger
Female older
Male older
Male younger
Female younger
100
can be used to study vascular reactions during stress provocations of the circulation. Furthermore, age and gender related
differences in systolic and diastolic reflection at rest are largely
maintained also during exercise, showing that the technique
used is well suited for studies of the arterial system in broad
populations.
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