Download Surrogate Measures of Arterial Stiffness

Editorial Commentary
Surrogate Measures of Arterial Stiffness
Do They Have Additive Predictive Value or Are They Only
Surrogates of a Surrogate?
Stéphane Laurent
R
Downloaded from http://hyper.ahajournals.org/ by guest on August 12, 2017
stroke mortality. These findings and statements call for
several comments.
First, AASI should not be confused with arterial stiffness.
A close univariate association between 2 parameters (AASI
and aortic PWV) does not imply a single mechanistic link.
For instance, although brachial PP and aortic PWV are
strongly linked, they represent 2 aspects of hemodynamics.
Pulse pressure increases when aortic stiffness increases because the pressure wave, which travels from the heart to the
periphery (during each cardiac cycle), is reflected at some
point, and returns to the heart. The stiffer the aorta, the faster
the return of the reflected wave, which superimposes on the
forward wave in late systole, thus increasing the amplitude of
PP and SBP in the ascending aorta, and to a lesser extent in
peripheral arteries. In addition, factors other than arterial
stiffness can influence the value of brachial PP, such as heart
rate, cardiac contractility, venous pressure, and amplification
phenomenon.4 – 6 Particularly, Li et al7 provided no demonstration that AASI remained significantly correlated to aortic
PWV after full adjustment for confounding factors.
Second, the hemodynamic significance of AASI, which is
inversely related to the slope of brachial DBP versus SBP, is
closer to brachial PP than to arterial stiffness. Indeed, by
contrast to what was discussed above, AASI remained significantly correlated to peripheral and central systolic augmentation after adjustment on confounding factors.7 Pathophysiological conditions and drugs can change PP and
augmentation index without changing aortic PWV, suggesting a predominant effect on reflectance points, heart rate, or
ventricular ejection, and no change in aortic stiffness.9
Third, because arterial stiffness, directly measured by
aortic PWV, is the final common pathway on which BP and
other CV risk factors operate, it may have a higher predictive
value than “surrogate” indexes. This may explain why the
predictive value of AASI for CV mortality and fatal stroke,
reported in the article by Dolan et al8 was lower than that
reported with aortic PWV by others.1–3 For instance, AASI
had no independent predictive value for CV mortality in the
population of the Irish Outcome Study, whereas aortic PWV
was an independent predictor of CV mortality in English
diabetic patients3 and French hypertensive patients.1 For fatal
stroke, the multiple adjusted relative hazard ratio for 1 SD
increase in AASI (1.21 [1.01 to 1.45], P⬍0.05), reported in
the article by Dolan et al,8 was lower than that observed with
aortic PWV in a French hypertensive population (1.39 [1.08
to 1.72], P⬍0.05; calculated from data of Reference 2) and no
longer significant when restricted to the hypertensive population of the Irish Outcome Study. To increase the sensitivity
of AASI, the author used a dichotomized value, comparing
ecent epidemiological studies have shown that arterial stiffness, measured through carotid-femoral pulse
wave velocity (PWV), has an independent predictive
value for cardiovascular (CV) events in several populations,
including patients with uncomplicated essential hypertension1,2 and type 2 diabetes.3 Arterial stiffness is thus an
intermediate end point for CV events, predicting CV events
independently of and beyond peripheral pulse pressure (PP).
Peripheral PP, central PP, and augmentation index, which
provide additional information on wave reflection, are considered “surrogates” of arterial stiffness, because their pathophysiological meaning is clearly different.4 – 6 Central PP and
augmentation index are dependent on the speed of wave
travel, the amplitude of reflected wave, the reflectance point,
and the duration and pattern of ventricular ejection, especially
with respect to change in heart rate and ventricular contractility. Aortic PWV, which is the speed of wave travel,
represents intrinsically arterial stiffness, according to the
Bramwell-Hill formula.4 – 6
Two articles7,8 in the present issue of Hypertension raise
the issue of the predictive value of “surrogates of arterial
stiffness” for CV events. Li et al7 studied the dynamic
relationship between diastolic blood pressure (DBP0 and
systolic blood pressure (SBP) in ambulatory blood pressure
monitoring (ABPM) data throughout the day and calculated a
novel index as 1⫺ the regression slope of DBP on SBP. This
index was named ambulatory arterial stiffness index (AASI)
on the basis that “average distending BP varies during the
day, and that the relation between DBP and SBP with this
changing distending BP largely depends on the structural and
functional characteristics of the large arteries.”8 The authors7
stated that it was a “novel measure of arterial stiffness” from
the demonstration that AASI closely correlated with aortic
PWV and the central and peripheral augmentation indexes. In
a companion article, Dolan et al8 determined AASI in 11 291
participants to the Dublin Outcome Study and showed its
independent predictive value for stroke mortality but not
cardiac mortality, in contrast to 24-hour PP, which had an
independent predictive value for cardiac mortality but not
The opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
From the Department of Pharmacology and Inserm, Hôpital Européen
Georges Pompidou, Paris, France.
Correspondence to Stéphane Laurent, Department of Pharmacology and
Inserm EMI 0107, Hôpital Européen Georges Pompidou, 20 rue Leblanc,
75015 Paris, France. E-mail [email protected]
(Hypertension. 2006;47:325-326.)
© 2006 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
DOI: 10.1161/01.HYP.0000200701.43172.9a
325
326
Hypertension
March 2006
Downloaded from http://hyper.ahajournals.org/ by guest on August 12, 2017
the 5% highest value to the 95% lowest. Even under these
conditions, the independent predictive value of AASI for CV
mortality (1.59 [1.23 to 2.04], P⬍0.05]) was much lower than
that of aortic PWV in a French hypertensive population (6.02
[3.05 to 11.85], P⬍0.0001; calculated from data of Reference 1).
Fourth, the authors8 state that the determination of AASI is
easier than that of aortic stiffness, since “ABPM is implemented in most hospitals and a growing number of family
practices,” whereas measurement of arterial stiffness “requires special equipment and trained observers.” Although it
is unfortunate that arterial stiffness is underused in clinical
practice for risk stratification, this is because of the absence
of guidelines rather than the difficulty of measurements.
Various apparatuses are currently available to easily determine aortic PWV in outpatient clinic facilities in less time
than an EKG, with no more training than for performing a
more disturbing 24-hour ABPM.4 –5
Finally, AASI is considered by the authors as a novel index
of arterial stiffness, thus adding one more parameter to the
already long list of surrogate indexes for arterial stiffness,
including augmentation index, augmentation pressure, central
PP, and brachial PP. This may reduce the understanding of an
already complex area of research and hamper the implementation of simple guidelines into clinical practice. Arterial
stiffness has demonstrated its surrogate value for CV events
in patients with end-stage renal disease (ie, that a reduction in
PWV could predict a reduction in CV events, independently
of the normalization of classical CV risk factors).10 The
impact of aortic stiffness reduction on CV mortality, coronary
events, and stroke remains to be established in other populations, particularly those at lower but still high CV risk. Thus,
instead of measuring the surrogate of a surrogate end point,
why not use the direct measurement of arterial stiffness
through aortic PWV, which has the largest amount of epidemiological evidence for its predictive value for CV events,
requires little technical expertise, and is considered as the
“gold standard” for arterial stiffness by most experts?
References
1. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux X, Guize L,
Ducimetière P, Benetos A. Aortic stiffness is an independent predictor of
all cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236 –1241.
2. Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B,
Boutouyrie P. Aortic stiffness is an independent predictor of fatal stroke
in essential hypertension. Stroke. 2003;34:1203–1206.
3. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG.
Aortic pulse-wave velocity and its relationship to mortality in diabetes
and glucose intolerance: an integrated index of vascular function? Circulation. 2002;106:2085–2090.
4. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE.
Clinical applications of arterial stiffness; definitions and reference values.
Am J Hypertens. 2002;15:426 – 444.
5. Van Bortel LM, Duprez D, Starmans-Kool MJ, Safar ME, Giannattasio C,
Cockcroft J, Kaiser DR, Thuillez C. Applications of arterial stiffness,
Task Force III: recommendations for user procedures. Am J Hypertens.
2002;15:445– 452.
6. Mackenzie IS, Wilkinson IB, Cockcroft JR. Assessment of arterial
stiffness in clinical practice. QJM. 2002;95:67–74.
7. Li Y, Wang JG, Dolan E, Gao PJ, Guo HF, Nawrot T, Stanton AV, Zhu
DL, O’Brien E, Staessen JA. Ambulatory arterial stiffness index derived
from 24-hour ambulatory blood pressure monitoring. Hypertension. 2006;
47:359 –364.
8. Dolan E, Thijs L, Li Y, Atkins N, McCormack P, McClory S, O’Brien E,
Staessen JA, Stanton AV. Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study. Hypertension. 2006;47:365–370.
9. Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ. Vasoactive drugs
influence aortic augmentation index independently of pulse-wave
velocity in healthy men. Hypertension. 2001;37:1429 –1433.
10. Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM.
Impact of aortic stiffness attenuation on survival of patients in end-stage
renal failure. Circulation. 2001;20:103:987–999.
Surrogate Measures of Arterial Stiffness: Do They Have Additive Predictive Value or Are
They Only Surrogates of a Surrogate?
Stéphane Laurent
Downloaded from http://hyper.ahajournals.org/ by guest on August 12, 2017
Hypertension. 2006;47:325-326; originally published online January 23, 2006;
doi: 10.1161/01.HYP.0000200701.43172.9a
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2006 American Heart Association, Inc. All rights reserved.
Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://hyper.ahajournals.org/content/47/3/325
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial
Office. Once the online version of the published article for which permission is being requested is located,
click Request Permissions in the middle column of the Web page under Services. Further information about
this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Hypertension is online at:
http://hyper.ahajournals.org//subscriptions/