Amplification of the Pressure Pulse in the Upper Limb in
Healthy, Middle-Aged Men and Women
Patrick Segers, Dries Mahieu, Jan Kips, Ernst Rietzschel, Marc De Buyzere, Dirk De Bacquer,
Sofie Bekaert, Guy De Backer, Thierry Gillebert, Pascal Verdonck, Luc Van Bortel;
for the Asklepios investigators
Downloaded from http://hyper.ahajournals.org/ by guest on June 14, 2017
Abstract—Central-to-peripheral amplification of the pressure pulse leads to discrepancies between central and brachial
blood pressures. This amplification depends on an individual’s hemodynamic and (patho)physiological characteristics.
The aim of this study was to assess the magnitude and correlates of central-to-peripheral amplification in the upper limb
in a healthy, middle-aged population (the Asklepios Study). Carotid, brachial, and radial pressure waveforms were
acquired noninvasively using applanation tonometry in 1873 subjects (895 women) aged 35 to 55 years. Carotid,
brachial, and radial pulse pressures were calculated, as well as the absolute and relative (with carotid pulse pressure as
reference) amplifications. With subjects classified per semidecade of age, carotid-to-radial amplification varied from
⬇25% in the youngest men to 8% in the oldest women. Amplification was higher in men (20⫾14%) than in women
(13⫾12%; P⬍0.001) and decreased with age (P⬍0.001) in both. Amplification over the brachial-to-radial path
contributed substantially to the total amplification. In univariate analysis, the strongest correlation was found with the
carotid augmentation index (⫺0.51 in women; ⫺0.47 in men; both P⬍0.001). In a multiple linear regression model with
carotid-to-radial amplification as the dependent variable, carotid augmentation index, total arterial compliance, and heart
rate were identified as the 3 major determinants of upper limb pressure amplification (R2⫽0.36). We conclude that, in
healthy middle-aged subjects, the central-to-radial amplification of the pressure pulse is substantial. Amplification is higher
in men than in women, decreases with age, and is primarily associated with the carotid augmentation index. (Hypertension.
2009;54:414-420.)
Key Words: cardiovascular physiology 䡲 blood pressure 䡲 large arteries 䡲 wave reflection 䡲 hemodynamics
I
t has long been demonstrated that, when the blood pressure
waveform is measured along the arterial tree, it changes
continuously in shape and amplitude.1,2 In large- and
medium-sized arteries, the systolic upstroke of the wave
generally becomes steeper from the central aorta toward the
periphery, whereas the amplitude also increases, mainly
through an increase in the peak value (systolic blood pressure) of the waveform. Overall, the minimum (diastolic) and
mean (mean blood pressure) values, and especially the
difference between both, change little from one location to
the other.3 These are well-known features described in
physiological textbooks, and these phenomena can be explained on the basis of wave travel and reflection. The heart
generates a forward-running pressure wave, which is reflected in the periphery. The measured pressure at any
location is, thus, composed of this forward component, as
well as backward components, arising from reflections.4,5 The
closer the blood pressure is measured to the reflection site (ie,
the further in the periphery), the earlier the forward and
backward waves will interact, leading to the steeper systolic
upstroke and the more peaked appearance of pressure waves.
This explains why the radial pressure wave is much more
peaked than the central aortic or carotid pressure wave. This
change in shape can be quantified via the so-called “form
factor,” expressing the ratio of the difference between its
mean and minimum value over the amplitude of a wave.
Until only a few years ago, pressure wave amplification
received little or no attention and was thought to be relevant
only when studying hemodynamics or arterial (patho)physiology. It may, however, have an important impact on clinical
patient management.6,7 Diagnosis and treatment of (hypertension and cardiovascular) patients is quasi solely on the basis
of the blood pressure values measured noninvasively using a
cuff-based approach at the level of the brachial artery (BA),
a peripheral vessel. Given the information above, it is clear
that systolic blood pressure at the BA overestimates central
Received March 22, 2009; first decision April 7, 2009; revision accepted May 22, 2009.
From the Biofluid, Tissue, and Solid Mechanics for Medical Applications, Institute Biomedical Technology (P.S., J.K., P.V.), Heymans Institute of
Pharmacology (D.M., J.K., L.V.B.), and Department of Molecular Biotechnology, Faculty of Bioscience Engineering (S.B.), Ghent University; and the
Departments of Cardiovascular Diseases (E.R., M.D.B., T.G.) and Public Health (D.D.B., G.D.B.), Ghent University Hospital, Ghent, Belgium.
P.S. and D.M. contributed equally to this article.
Correspondence to Patrick Segers, Ghent University, Institute Biomedical Technology, De Pintelaan 185, B-9000 Gent, Belgium. E-mail
[email protected]
© 2009 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.109.133009
414
Segers et al
Pressure Pulse Amplification in the Upper Limb
415
blood pressure, which is the blood pressure faced by the heart.
This should pose no specific problem if the relation between
central and brachial blood pressures was unequivocal. However, this is not the case: pressure amplification is determined
by wave travel and reflection phenomena, and these change
not only from one subject to another but also with (patho)
physiological changes within the individual8 –10 and with administration of drugs affecting the heart rate.11 In recent work,
McEniery et al9 have shown that pressure amplification is
directly related to heart rate and height (the taller and the higher
the heart rate, the higher the amplification) and inversely related
to age and a number of cardiovascular risk factors. The aim of
this study was to assess the magnitude and correlates of
central-to-peripheral amplification in the upper limb in the
Asklepios Study cohort of healthy, middle-aged men and
women.12
defined as follows: Q1, 35 to 40 years; Q2, 41 to 45 years; Q3, 46 to
50 years; and Q4, 51 to 56 years of age. Effects of age and sex were
assessed with ANOVA techniques, using sex and age stratum as
fixed factors. Correlation between variables was assessed using
Pearson correlation analysis. P values ⬍0.05 were considered as
statistically significant. To study the determinants of carotid-toradial amplification, a forward multiple linear regression model was
constructed with relative carotid-to-radial amplification as the dependent variable. As independent variables, we included parameters
with a correlation coefficient ⬎0.15 in univariate analysis. In
addition to basic clinical and morphological data, these parameters
included carotid-femoral pulse wave velocity and total arterial
compliance (PP method18) as measures of arterial stiffness, the
carotid augmentation index (AIx) and reflection magnitude (ratio of
backward and forward pressure wave amplitudes) as measures of
wave reflection, and systemic vascular resistance. We refer to Segers
et al17 for details on how these parameters were determined. All of
the analyses were performed using SPSS 15 (SPSS Inc).
Materials and Methods
General clinical characteristics of the population, stratified
for men and women and as a function of age and sex, are
provided in Table 1.
Results
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The total Asklepios Study cohort consists of 2524 volunteers (age
between 35 and 55 years), and carotid artery (CA), BA, and radial
artery (RA) pressure waveforms were acquired noninvasively using
applanation tonometry in 1873 subjects (895 women). The study was
approved by the local ethics committee, and written, informed
consent was obtained from all of the subjects. Details on the study
design and methodology can be found elsewhere.12
Subjects were allowed 10 to 15 minutes of rest in a temperaturecontrolled environment before the examinations. First, systolic blood
pressure (SBP) and diastolic blood pressure (DBP) were measured in
the supine position with a validated oscillometric blood pressure
monitor, the Omron HEM-907 (Omron Matsusaka Co Ltd), followed
by brachial, radial, and carotid tonometry. These measurements were
done using a previously described custom-built acquisition system
consisting of a pen tonometer (SPT 301, Millar Instruments) and
dedicated software developed in Matlab (The MathWorks).13 Each
recording consisted of a 20-second window of raw data, and an
averaged waveform was constructed from ⱖ10 cardiac cycles.
To quantify the shape of the averaged carotid, brachial, and
radial waveforms, the form factor14(FF) was calculated as follows:
FF⫽[mean(Pwf)⫺min(Pwf)]/[max(Pwf)⫺min(Pwf)]
where Pwf is the measured pressure waveform. For a triangular
waveform, the FF value is 0.5, whereas it tends toward 1 for more
rectangular-shaped waveforms. It is the percentage of the amplitude
of the waveform to be added to the minimal value (min[Pwf]) to
obtain the mean value (mean[Pwf]). As such, when applying the
one-third rule used to estimate mean arterial blood pressure (MAP)
from DBP and SBP, one assumes a FF of 33%.
For the calibration of the tonometer waveforms, we applied the
previously described calibration scheme.15,16 The BA waveforms
were first calibrated using DBPBA and SBPBA measured at the BA,
and MAP was estimated as the mean value of this calibrated
waveform. The radial and CA waveforms were subsequently calibrated on the basis of DBPBA and MAP estimated as the mean value
of this calibrated waveform. Pulse pressure (PP) was defined as the
amplitude of these calibrated waveforms and derived at the CA
(PPCA), BA (PPBA), and RA (PPRA). As described by Segers et al,17
brachial tonometry could not be reliably measured within the allotted
time frame in 417 subjects. These subjects tended to be more obese
(body mass index: 26.6⫾4.6 versus 24.9⫾3.6 kg/m2; P⬍0.001) than
subjects for which the tonometry was performed without difficulties.
The absolute PP amplifications from carotid-to-brachial, brachialto-radial, and carotid-to-radial were calculated as the differences in
the corresponding PPs. The relative carotid-to-brachial and carotidto-radial PP amplifications were calculated as (PPBA⫺PPCA)/PPCA
and (PPRA⫺PPCA)/PPCA, respectively.
Data are presented as mean⫾SD. Subjects were stratified according to sex and subdivided into 4 half-decades of age (Q1 to Q4),
Waveform Characteristics: The Form Factor
In both men and women, the form factor was highest at the CA
(population mean: 44.0⫾3.2%), and decreased toward the BA
(42.4⫾3.3%) and RA (38.0⫾3.3%). The difference in the form
factor (Table 2 and Figure 1) between men and women is
smallest at the level of the CA, with a mean value of 44.2⫾3.3%
in women and 43.9⫾3.1% in men (P⫽0.096). At this site, it
decreases with age in women, whereas the trend to decrease with
age in men was less strong. At the BA, the form factor was
higher in women (43.7⫾3.1%) than in men (41.2⫾3.0%;
P⬍0.001). It increased with age in men (P⬍0.001), whereas
there was no effect of age in women (P⫽0.362). The difference
in the form factor between men and women is also present at the
level of the RA (39.5⫾2.9% versus 36.7⫾3.1%; P⬍0.001), with
an increase with age in both men and women (P⬍0.001).
Carotid-to-Radial Amplification
With subjects classified per semidecade of age, carotid-toradial amplification varied from ⬇25% in the youngest men
to 8% in the oldest women. Amplification was higher in men
(20⫾14%) than in women (13⫾12%; P⬍0.001) and decreased with age (P⬍0.001) in both (Table 2 and Figure 2).
The difference between sexes was such that, over the studied
age range, the amplification in the oldest men (age 50 to 55
years) was of the same magnitude as in the youngest women
(age 35 to 40 years), ie, ⬇17%. The amplification over the
brachial-to-radial path contributed substantially to the total
amplification, explaining most of the amplification in men
and practically all of the amplification in women. In absolute
values, the average difference between carotid and radial PPs
was 8.3⫾6.6 mm Hg in our population, varying from 12.7⫾
6.8 mm Hg in the youngest men to 4.5⫾5.7 mm Hg in the
oldest women category.
Correlates and Determinants of
Carotid-to-Radial Amplification
In what follows, all of the reported correlation coefficients
have P values of ⬍0.001. Carotid-to-radial amplification was
416
Hypertension
Table 1.
August 2009
Basic Clinical Data and Parameters of Large Artery Stiffness and Wave Reflection
Age Categories, y
Parameter
35 to 40
41 to 45
P
46 to 50
51 to 56
Age
Sex
Interaction
No. of subjects
F (N⫽895)
247
231
208
209
M (N⫽978)
236
257
237
248
F
38.2⫾1.8
43.4⫾1.5
48.3⫾1.5
53.8⫾1.7
M
38.3⫾1.8
43.6⫾1.4
48.5⫾1.4
53.9⫾1.7
F
64.0⫾10.1
64.3⫾11.9
65.8⫾12.1
65.9⫾10.7
M
79.6⫾11.4
79.7⫾11.3
81.9⫾11.7
80.8⫾11.2
Age, y
⬍0.001
0.142
0.819
0.010
⬍0.001
0.907
⬍0.001
⬍0.001
0.807
⬍0.001
⬍0.001
0.707
⬍0.001
⬍0.001
0.017
⬍0.001
⬍0.001
0.055
0.162
⬍0.001
0.035
⬍0.001
0.154
0.722
⬍0.001
⬍0.001
0.106
⬍0.001
0.002
0.097
⬍0.001
⬍0.001
0.101
⬍0.001
⬍0.001
0.014
Weight, kg
Height, cm
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F
165.1⫾5.9
163.9⫾6.0
162.5⫾5.9
161.4⫾5.4
M
177.4⫾6.4
175.9⫾6.2
175.1⫾6.5
174.2⫾6.0
F
23.4⫾3.5
23.9⫾4.1
24.9⫾4.3
25.3⫾3.9
M
25.2⫾3.3
25.7⫾3.2
26.7⫾3.5
26.6⫾3.5
F
123.8⫾14.3
125.8⫾14.5
129.7⫾15.2
136.1⫾17.1
M
130.4⫾10.5
133.0⫾12.7
134.9⫾14.4
137.7⫾16.7
F
73.5⫾11.4
74.5⫾10.3
75.6⫾10.2
77.3⫾10.8
M
73.8⫾9.3
78.1⫾10.8
79.4⫾10.0
80.0⫾11.3
F
65.1⫾9.2
65.4⫾8.3
64.9⫾8.3
64.5⫾8.8
M
60.4⫾8.5
60.8⫾8.9
63.2⫾11.4
61.6⫾10.0
F
5.92⫾1.08
6.17⫾1.23
6.65⫾1.19
7.24⫾1.75
M
5.89⫾0.89
6.31⫾1.07
6.79⫾1.17
7.34⫾1.85
F
0.97⫾0.25
0.93⫾0.24
0.90⫾0.25
0.79⫾0.26
M
1.19⫾0.34
1.19⫾0.33
1.15⫾0.31
1.11⫾0.33
F
0.46⫾0.08
0.48⫾0.09
0.48⫾0.09
0.52⫾0.10
M
0.44⫾0.08
0.48⫾0.09
0.48⫾0.09
0.49⫾0.09
F
14.63⫾12.46
18.98⫾10.84
22.36⫾12.89
28.12⫾10.59
M
0.90⫾13.29
8.95⫾13.69
11.84⫾12.42
16.80⫾12.78
F
1.29⫾0.30
1.31⫾0.29
1.32⫾0.30
1.45⫾0.38
M
1.15⫾0.24
1.19⫾0.29
1.18⫾0.27
1.21⫾0.29
BMI, kg/m2
Brachial SBP, mm Hg
Brachial DBP, mm Hg
HR, bpm
PWV, m/s
Ctot, mL/mm Hg
Pb/Pf, ⫺
AIx, %
SVR mm Hg/mL per s
F indicates female; M, male; PWV, carotid-femoral pulse wave velocity; Ctot, total arterial compliance; Pb/Pf, reflection magnitude;
SVR, systemic vascular resistance; BMI, body mass index. P value for age follows from a model including age and sex and applies
to both. It was, however, verified that the significance of the relation with age persisted in subgroup analysis.
associated with age (correlation coefficient: ⫺0.26 in women
and ⫺0.24 in men, respectively), heart rate (0.25/0.22), mean
blood pressure (⫺0.24/⫺0.23), height (0.12/0.18), weight
(0.12/0.14), total arterial compliance (0.24/0.24), vascular
resistance (⫺0.30/⫺0.31), reflection magnitude (⫺0.26/
⫺0.27), and carotid-femoral pulse wave velocity (⫺0.19/
⫺0.15). The strongest correlation in univariate analysis,
however, was found with the AIx (⫺0.51 in women; ⫺0.47 in
men; see also Figure 3). In a multiple linear regression model
with carotid-to-radial amplification as the dependent variable,
AIx, total arterial compliance, and heart rate were identified
as the 3 major determinants of upper limb amplification,
entering the model in that order. The total variance (R2)
explained by the model was 0.30 in men and 0.31 in women,
Segers et al
Table 2.
Pressure Pulse Amplification in the Upper Limb
417
Form Factor and PP at the CA, BA, and RA
Age Categories, y
Waveform Parameter
P
35 to 40
41 to 45
46 to 50
51 to 56
Age
Sex
Interaction
F
45.1⫾3.5
44.6⫾2.8
43.8⫾3.1
43.1⫾3.4
⬍0.001
0.096
0.001
M
44.0⫾2.9
44.1⫾3.0
44.2⫾3.0
43.4⫾3.6
F
43.8⫾3.2
44.0⫾3.1
43.6⫾3.0
43.5⫾3.1
0.013
⬍0.001
0.001
M
40.4⫾3.4
41.4⫾3.0
41.6⫾2.5
41.5⫾2.8
F
38.9⫾3.1
39.7⫾2.9
39.5⫾3.0
39.9⫾2.6
⬍0.001
⬍0.001
0.001
M
35.4⫾3.1
36.7⫾2.9
37.3⫾3.0
37.6⫾3.0
F
49.2⫾9.8
50.9⫾10.0
54.1⫾11.8
59.7⫾15.0
⬍0.001
0.332
⬍0.001
M
52.1⫾9.7
51.7⫾8.8
52.4⫾9.9
55.7⫾12.1
F
50.3⫾8.2
51.4⫾9.2
54.1⫾10.8
58.8⫾12.4
⬍0.001
⬍0.001
⬍0.001
M
56.5⫾8.9
54.9⫾8.3
55.5⫾9.1
57.7⫾10.7
F
56.8⫾10.3
57.1⫾10.6
60.1⫾13.1
64.3⫾14.7
⬍0.001
⬍0.001
⬍0.001
M
64.8⫾12.0
62.2⫾10.7
62.0⫾11.0
64.0⫾13.0
Carotid form factor, %
Brachial form factor, %
Radial form factor, %
Carotid PP, mm Hg
Radial PP, mm Hg
F indicates female; M, male; PP, pulse pressure.
with the major part explained by AIx (R2 0.22 in men and
0.26 in women), whereas both total arterial compliance and
heart rate each equally explained the remaining variance.
Pooling data of men and women, total R2 was 0.36, with 29%
of the variance explained by AIx, whereas both total arterial
compliance and heart rate each explained an additional 3%.
Discussion
It is beyond any doubt that the pressure pulse is amplified
from the central aorta toward the RA. Subjects of debate are,
however, the absolute value (in millimeters of mercury) of
this amplification and how the amplification is distributed
over the aorta-brachial-radial pathway. Assuming CA pressure to be a surrogate for central aortic pressure, and (the
difference between) mean and DBP to remain constant, our
data allow us to answer some of these questions and to
speculate on others.
46
As illustrated in Figure 2 (right), the relative increase in PP
from the CA to the RA is highest (25%) in the youngest men
and lowest (8%) in the oldest women categories. In both men
and women, it decreases with age. The carotid-to-radial
amplification that we found is lower than the values reported
recently by McEniery et al,9 who found central-to-brachial
amplifications of 44% in healthy subjects (mean age: 45
years) and up to 54% in a subgroup of (young) smokers.
Assuming a constant difference between MAP and DBP
throughout the large arteries, it is easily demonstrated that
PPBA/PPCentral⫽FFCentral/FFBA. Assuming an average form
factor of the central pressure wave of 45%,14 a central-tobrachial amplification of 44% would imply a brachial form
factor of 31%. This is a very low value, indicative for highly
peaked waveforms. This value is substantially lower than the
form factor of 40% from an invasive study19 and lower than
the values at the RA in the present study, where we found the
waveform to be sharper than at the BA. The somewhat higher
35-40
41-45
46-50
51-56
44
Form Factor (%)
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Brachial PP, mm Hg
42
40
38
36
Men
Women
34
CA
BA
RA
CA
BA
RA
Figure 1. Form factor of the noninvasively measured pressure wave at the CA, BA, and RA in men (left) and women (right).
418
Hypertension
August 2009
brachial to radial
carotid to brachial
Men
12
0.30
Women
relative increase in PP
from carotid to radial artery
PP increase from
carotid to radial artery (mmHg)
14
10
8
6
4
2
0
-2
35-40 41-45 46-50 51-56
35-40 41-45 46-50 51-56
age range
age range
Men
Women
0.25
0.20
0.15
0.10
0.05
0.00
-0.05
35-40 41-45 46-50 51-56
35-40 41-45 46-50 51-56
age range
age range
resting heart rates may contribute to this difference, but we
speculate that also the calibration procedure followed by
McEniery et al9 (who did not account for any brachial-toradial pressure amplification on calibration of the RA pressure waveforms) explains at least part of the discrepancy.
When the unamplified RA tonometer waveforms are subsequently used to estimate central blood pressure using a
transfer function, the estimated central blood pressure will,
artificially, be too low, resulting in an apparently high
central-to-brachial amplification.20
The absolute amplification from the carotid-to-radial pathway was ⬇13 mm Hg in the youngest men group and
decreased to ⬇5 mm Hg in the oldest women. Overall, the
average difference between central and radial PPs was
8.3⫾6.6 mm Hg. With the knowledge that carotid pressure is
⬇2 mm Hg higher than central aortic pressure, we estimate
the average aorta-to-radial amplification in our population in
the order of 10 mm Hg. This is (somewhat) lower than the
value of 12 mm Hg found by McEniery et al9 in healthy
subjects (mean age: 45 years). The major difference between
Relative Carotid-to-Radial Amplification (-)
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Figure 2. Absolute (left) and relative (right) amplifications of the pressure pulse from the CA to the BA (filled bars), and from the BA to
RA (hatched bars). The relative amplification was calculated with carotid PP as the reference.
0.8
Women
Men
0.6
0.4
0.2
0.0
- 0.2
-60
- 40
- 20
0
20
40
60
80
carotid augmentation index (%)
Figure 3. Relation between carotid AIx and relative carotid-toradial amplification in men and women. Solid line is the regression line in women (R2⫽0.26) and the dashed line is the regression line in men (R2⫽0.22).
our study and the work of McEniery et al9 (based on the
SphygmoCor device) is that they ascribe this amplification
entirely to central-to-brachial amplification, without any further amplification toward the RA. This is in contrast with our
data, because we found an important contribution to the
amplification along the brachial-to-radial pathway (see Figure 2), confirming previous findings.21
Our data confirm that pressure amplification depends on
many factors. In agreement with data reported previously, we
found pressure amplification to decrease with age and increase with heart rate and height.9 The strongest (negative)
association, however, was found with the carotid AIx, confirming previous findings.10 This is not surprising, because
AIx quantifies SBP augmentation attributed to wave reflection and depends on magnitude and timing of reflected waves.
These are the same factors affecting pressure augmentation.
In a multiple linear regression model, AIx alone explained
⬇30% of the variance in carotid-to-radial amplification,
which is virtually the same number as reported by Protogerou
et al.10 Other factors contributing to some extent were total
arterial compliance and heart rate, explaining another 6% of
the variance. Nevertheless, the fact that only ⬇36% of the
variance in amplification can be explained indicates that it is
a complex multifactorial phenomenon. We repeated the
multiple linear regression model (with the relative carotid-toradial amplification as the independent variable) adding
glucose levels, high-density lipoprotein and total cholesterol
levels, body mass index or waist circumference, nicotine
exposure, and calculated 10-year Framingham risk score as
independent variables, but none of these parameters entered
the model and significantly improved the R2 value. This may
be attributable to the fact that the middle-aged Asklepios
population is a low-risk population with a narrow age range.
McEniery et al9 found risk factors (hypertension, cardiovascular disease, smoking, hypercholesterolemia, and diabetes
mellitus) to each explain ⬇1% of the variance in the
amplification ratio.
Our findings depend, in part, on brachial pressure waveforms obtained via tonometry, which is still subject to
Segers et al
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debate.22 The procedure is not feasible in all subjects (it is
more difficult in obese subjects), requires a highly skilled and
trained operator, and the local anatomy of the BA may be not
as well suited for applanation tonometry as the RA. In our
Asklepios population, we could not record BA pressure
waveforms with satisfactory quality within a reasonable time
frame in 417 subjects (⬇18% of the population).17 However,
when feasible, the recording of the waveforms was qualitatively judged as reliable as on the CA or RA by the operator.
The values that we found for the form factor at the BA (Table
2 and Figure 1) are, as one might expect, in between the value
at the CA and RA and close to the value of 40% reported
recently by Bos et al (based on invasive data).19 Nevertheless,
the values that we found are somewhat higher, leading to a
more pronounced brachial-to-radial contribution to the total
amplification than one would find when using a value of
40%. Note, however, that the reported values of relative
carotid-to-radial-amplification (Figure 2, right) are independent of the brachial tonometer measurements; these only
interfere when assessing the carotid-to-brachial and brachialto-radial contributions.
The form factor quantifies the shape of the wave, but it also
expresses the percentage of PP to add to DBP to estimate
mean blood pressure. When using the widely applied rule of
thumb to estimate mean blood pressure, a form factor of one
third (33%) is assumed. It is clear from our data that this
value is too low and that the one-third rule to estimate MAP
should be reconsidered, especially when using MAP for
tonometer calibration purposes. Anyhow, given the strong
dependence of the brachial pressure wave shape and amplitude on all factors impacting pressure amplification, one fixed
formula to estimate MAP from DBP and SBP is doomed to
show some flaws.
The further away from the heart, the more important the
difference in form factor becomes between men and women.
At the BA, the form factor is ⬇2% lower in men, and this
difference increases to ⬇3% at the level of the RA. It is also
observed that the carotid and brachial form factors are close
in women, resulting in very little difference between carotid
and brachial PPs. We speculate that this is related to the different
body proportions in men and women, with the difference
between the aorta-carotid and the aorta-brachial distances being
larger in men than in women. Although we did not measure
detailed anthropometric data, the distance between the suprasternal notch and the CA was only 0.4 cm less in women,
whereas the difference in the distance between the suprasternal notch and RA was ⬎6 cm in our population, which
supports this view.
It is clear that our study is not free from limitations, the
most important ones being the relatively narrow age range of
our study and obviously the absence of invasive data. Nevertheless, it is clear that population data can only be acquired
with noninvasive means, especially in young to middle-aged
apparently healthy subjects as in the Asklepios population,
where pressure amplification is most obvious. Also, although
the validity of BA applanation tonometry is still debated, we
have clearly demonstrated carotid-to-radial amplification independent of this measurement making use of the (ratio of
the) carotid and radial form factors.
Pressure Pulse Amplification in the Upper Limb
419
Perspectives
Because of the amplification of the pressure pulse along the
BA and RA of the upper limb, peripheral blood pressure does
not accurately reflect central blood pressure. A major inconvenience is the highly variable nature of the magnitude of this
amplification. It is lower in women than in men, decreases
with age, and is inversely related to heart rate. In our
middle-aged population of apparently healthy men and
women, we found carotid AIx to be the best predictor of the
magnitude of the amplification, with an inverse relation
between both. Whether quantification of the magnitude of
amplification (or, rather, the lack of pressure amplification)
would be useful in the assessment of cardiovascular risk
remains to be demonstrated. Given that amplification diminishes with age and with a strong negative association with
carotid AIx, its additional discriminative power might be low
in older populations at high cardiovascular risk. It is also
noteworthy that the observed magnitude of amplification
depends on the method used to assess the central blood
pressure, with the calibration of the noninvasively measured
waveforms being a determining factor.
In conclusion, the central-to-radial amplification of the
pressure pulse is substantial in healthy middle-aged subjects.
The amplification is higher in men than in women, decreases
with age, and is primarily negatively associated with the
carotid AIx.
Sources of Funding
This research was funded by Research Foundation Flanders (FWO)
research grant G.0427.03 (to the Asklepios Study).
Disclosures
None.
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Amplification of the Pressure Pulse in the Upper Limb in Healthy, Middle-Aged Men and
Women
Patrick Segers, Dries Mahieu, Jan Kips, Ernst Rietzschel, Marc De Buyzere, Dirk De Bacquer,
Sofie Bekaert, Guy De Backer, Thierry Gillebert, Pascal Verdonck and Luc Van Bortel
for the Asklepios investigators
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Hypertension. 2009;54:414-420; originally published online June 22, 2009;
doi: 10.1161/HYPERTENSIONAHA.109.133009
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2009 American Heart Association, Inc. All rights reserved.
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