Editorial Commentary
Pathway for Elimination of Distance Measurement
in Studies of Pulse Wave Velocity
Alberto Avolio, Junli Zuo, Isabella Tan, Mark Butlin
See related article, pp 937–945
T he classic studies of Bramwell and Hill1 in 1922 relating
elasticity of the artery wall to the speed of the traveling
pulse wave led to measurement of pulse wave velocity (PWV)
in large population groups to characterize age-related changes
in arterial stiffness.2,3 These early studies, among others, all
showed a general increase in PWV with age; however, there
was substantial variation in values of aortic PWV at similar
ages between populations of different ethnic origin and geo-
graphic location.4 Reasons for this are varied but include vari-
able rates of vascular aging in different populations exposed to
different environmental and dietary factors and variations in
age-related increase in blood pressure. However, an important
consideration is also the variation in methodology for measure-
ment of pulse transit time and travel distance to compute PWV.
With high fidelity recordings of the arterial pulse, repro-
ducible estimates of pulse transit time can be obtained by
identifying a fiducial point close to the foot of the wave. For
mechanical sensors, the dispersive nature of the skin and tis-
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sue overlying an artery generally attenuates high-frequency
components, and so the foot of the pulse is not readily identi-
fied. This may have been a contributing factor to the variation
in PWV determined by mechanical strain-type transducers in
some of the early PWV studies. Notwithstanding the accuracy
of pulse transit time estimation, its relation to arterial stiffness
(and PWV) is determined by the path length traveled by the
propagating pulse, a quantity which is not possible to measure
with a certain degree of accuracy without physically visual-
izing the morphology of the arterial segments and branching
structure. Hence, an estimate of the path length is obtained by
large-scale linear distances on the body surface (Figure).
In this issue of Hypertension, Weir-McCall et al6 take a sig-
nificant leap forward and propose to completely eliminate the
physical measurement of distance and to replace it with a cal-
culated value using the subject’s anthropometric information.
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the Department of Biomedical Sciences, Faculty of Medicine
and Health Sciences, Macquarie University, Sydney, Australia (A.A., I.T.,
M.B.); and Department of Geriatrics, Ruijin Hospital North, Shanghai
Jiaotong University School of Medicine, China (J.Z.).
Correspondence to Alberto Avolio, Department of Biomedical
Sciences, Faculty of Health and Medical Sciences, 2 Technology Place,
Macquarie University, Sydney NSW 2109, Australia. E-mail alberto.
avolio@mq.edu.au
(Hypertension. 2018;71:819-821.
DOI: 10.1161/HYPERTENSIONAHA.118.10839.)
© 2018 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.118.10839
819
The investigators make a convincing case that this calculated
distance does not alter significant associations of carotid–fem-
oral PWV with factors of cardiovascular risk but significantly
reduces intercenter variability, the main issue with comparing
PWV studies across different investigations. Other previous
studies7 also attempted to derive a distance formula for PWV
from anthropometric parameters, albeit from smaller cohorts;
however, the study by Weir-McCall et al6 is the first to explic-
itly compare the calculated path length with the true travel
distance between the carotid and femoral arteries.
The study involved analysis of whole-body magnetic reso-
nance angiograms in 1183 subjects (TASCFORCE [Tayside
Screening for Cardiovascular Events] group) from which accu-
rate vessel centerline path lengths were traced between carotid
and femoral arteries. From this cohort, a formula was derived
for carotid–femoral distance with specific coefficients for
age, height, weight, heart rate, and a different constant value
for males and females (Figure). The formula evaluated in the
study was for the right carotid–femoral path length. However,
a formula was also calculated for the left carotid–femoral path
length, and this formula has a term for diastolic pressure. The
diastolic pressure term was not explicitly explained because
the decision was made to only use the right side in accordance
with guideline recommendations.8 The distance formula was
validated in a much smaller cohort of 128 subjects who also
underwent whole-body magnetic resonance angiograms. The
study assessed effects on risk factor associations, prediction
of major events, and disease discrimination when PWV was
recalculated using the derived distance. This was done in 2
separate cohorts consisting of 1242 subjects from the mul-
ticenter SUMMIT study (Surrogate Markers of Micro- and
Macrovascular Hard End-Points for Innovative Diabetes
Tools) and 825 subjects from the Caerphilly Prospective
Study. Thus, 4 separate centers were involved in which the
intercenter differences were evaluated.
The validation study showed a significant but small mean
error of 7.8 mm (with limits of agreement from −41.1 to 56.7
mm). When compared with the body surface distance mea-
surements, the derived distance preserved the PWV associa-
tions with age and blood pressure but eliminated associations
with body mass index. Importantly, the intercenter PWV dif-
ferences were not eliminated when using the body surface
distance and accounting for covariates (age, sex, and mean
blood pressure). However, differences between study centers
were eliminated by the derived distance formula. The signifi-
cant association of carotid–femoral PWV and cardiovascular
mortality was preserved using both measured and derived
path length.
 820  Hypertension  May 2018

Figure.  Distances for calculation of carotid–femoral pulse wave velocity (PWVcf) from the pulse transit time registered between carotid
artery (C) and femoral artery (f) recording sites. PWVcf can be calculated using the subtraction method (Equation 1) or direct distance
method (Equation 2). In the subtraction method, the distance between the carotid artery and suprasternal notch (S) (dsc) is subtracted
from the distance between the suprasternal notch and femoral artery (dsf). This is also described as the 3-point method. A variation of
this is the 4-point method where the distance dsf is the sum of the distance between the suprasternal notch and umbilicus and distance
between umbillicus and femoral site. In the direct distance method, the path length is 80% of the direct distance between carotid and
femoral sites as recommended by guidelines on measurement of PWV.5 In the study of Weir-McCall et al,6 the formula for the path length
(shown on right of figure) between right carotid and femoral arteries corresponding to the measured transit time was generated using the
subtraction method and validated only in cohorts using the subtraction method for calculation of PWVcf, taking into account the 3 or 4
point approach.
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The derived formula for path length in the study by Weir-
McCall et al6 has positive coefficients for age, height, and
weight but a negative coefficient for heart rate (Figure). This
is somewhat counterintuitive as it is not evident why arter-
ies, especially the aortic trunk and large limb arteries, would
reduce in length with increasing heart rate. The authors
address this apparent anomaly by speculating on the associ-
ation of heart rate, sympathetic activity, and stroke volume
affecting vascular distension. Notwithstanding the unexpected
association with heart rate, the mean error in derived distance
is surprisingly small (<1 cm), suggesting that the negative
heart rate coefficient may not be a mere statistical effect, and
the intriguing observation warrants further investigation.
The study by Weir-McCall et al6 is necessarily limited by
the age distribution in the cohorts of the 4 centers. Hence, there
was a substantial discrepancy in the age distribution of the
training cohort (mean age 54.1 years) and validation cohorts
(mean age 68.4 and 72.3 years). Therefore, it is not certain to
what extent the formula could be applied to subjects below
the age of 50 years. An additional limitation of the study is
that PWV using the derived formula was not compared with
PWV using recommended distance of 80% of the direct linear
carotid–femoral distance.5,8
The study provides a convincing demonstration that for
PWV studies in large cohorts, the physical measurement of
carotid–femoral distance could be conceivably eliminated
and replaced by a derived distance. This would minimize the
difference that is present between different centers because
of aberrations in obtaining reliable body surface distance
between measuring sites. The analysis shows that all signifi-
cant associations of carotid–femoral PWV with cardiovascu-
lar risk factors are preserved. However, this does not imply
that risk reclassification would be altered.
Methodological and intercenter differences in PWV mea-
surement were at the forefront of considerations for interpre-
tation of the high values of aortic PWV found in a northern
Chinese community in urban Beijing compared with those of
previous studies conducted in Western populations.2–4 Given
the differences in methodologies, it was not possible to arrive
at learned conclusions as to whether a Chinese population,
with generally accepted low prevalence of atherosclerosis, had
much higher aortic stiffness compared with Western popula-
tions at the same age. A second study in a southern Chinese
community in rural Guangdong province conducted by the
same investigators using the same instrumentation and simi-
lar methodology for pulse transit time and distance measure-
ments provided powerful evidence, showing a wide separation
of age-related changes in aortic PWV. The rural community
achieved similar values of PWV some 30 years later, con-
comitant with similar delay in the prevalence of hypertension,
with the likely cause being the large difference in dietary salt
between northern urban and southern rural Chinese communi-
ties.9 These studies, controlled for methodological differences,
have provided strong supporting evidence for the value of reli-
able PWV measurements in populations with differences in
cardiovascular risk.
Experience with PWV studies to date has suggested
that across different investigations, population groups, and
 Avolio et al   Pulse Wave Velocity With Calculated Distance   821
investigators, given the differences in devices and meth-
odologies as well as variable tolerances in manual mea-
surements of body surface distances using flaccid tape
measures, reliable comparisons and meaningful interpreta-
tions could only be made from highly controlled studies.
That is, the methodological variability between different
centers and investigations can obfuscate potentially signifi-
cant physiological differences. This has been acknowledged
by leading investigators and professional societies in the
field, with attempts at standardizing distance measurements
so as to avoid repeated errors by minimizing the number
of readings. For carotid–femoral distance, a single direct
measurement is suggested between sites, and the distance
for calculation PWV is 80% of that measurement5 (Figure).
This method has been suggested to be used to normalize
differences across centers so as to compile large databases
of reliable normal values.10
The suggestion by Weir-McCall et al6 that the measure-
ment of distance be eliminated and replaced by a calculated
value deserves consideration, specifically for large cohorts
and multicenter studies. However, it is not yet clear how it
would improve PWV variability in individual measurements,
although with a fixed calculated distance, it would be expected
to reduce the combined source of error because of distance
and pulse transit time. Notwithstanding some of the inherent
limitations, the study by Weir-McCall et al6 provides suffi-
cient information to enable future studies using this formula,
which could be incorporated in devices that are used to mea-
sure pulse transit time. However, an important caveat in the
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application of the formula is that it is necessarily related to the
specific phenotype of the population of the cohorts, mainly
white European. Hence, for wider application, it is necessary
that the derivation of the formula be extended to other popula-
tions with different body stature, different ethnic origin, and
geographic location.
Disclosures
None.
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