Pulse Wave Velocity (PWV)

Evaluation of Vascular Function in Hemodialysis
Patients: Small Artery Elasticity Index (SAE)
Correlates with Pulse Wave Velocity (PWV)
Summer 2011
Medical Scholars Program
Allison M. Dubner, John J. White, Gaston K. Kapuku, David M. Pollock, Jennifer S. Pollock, and William D. Paulson
Department of Nephrology, Summer Medical Scholar Program,
Georgia Health Sciences University, Augusta, GA
Introduction
Arteriosclerosis is a major cause of cardiovascular
disease and mortality in end-stage renal disease
(ESRD) [1,2]. Arteriosclerosis is characterized by
arterial stiffening, with high arterial systolic and pulse
pressures [1-6]. These changes follow from the loss
of dampening function of arteries, which causes an
increase in pulse wave velocity. In a normal vascular
circuit, arterial pulse waves are reflected back from
the periphery and branch points, and these reflected
waves augment diastolic
pressure, thereby
enhancing coronary perfusion. However, pulse waves
travel more quickly in a stiff artery. Thus, reflected
waves may return during systole, thereby augmenting
systolic pressure and reducing diastolic pressure.
This helps explain enhanced cardiovascular mortality
in ESRD [7-10]. Thus, measurement of pulse wave
velocity (PWV) is considered the gold standard for
evaluating arterial stiffness and vascular function.
A second method of measuring vascular health is
flow mediated dilatation (FMD). FMD measures
reactive dilatation of the brachial artery following
release of nitric oxide. Stiff arteries generally
demonstrate poor dilatation in response to nitric oxide
[11,12]. This technique can be used to detect
vascular dysfunction, but requires a highly trained
sonographer and is difficult to perform.
Although PWV and FMD can be used to evaluate
cardiovascular disease in ESRD, these tests may not
be fast and easy enough for widespread use.
Measurement of arterial elasticity may meet this need
since the test is quick and requires no significant
training to perform. Additionally, small artery elasticity
index (SAE) has been shown to correlate with clinical
outcomes in both ESRD and non-ESRD patients
[13,14]. In this project, we compared these three tests
of vascular function to determine the relation between
SAE and the two established measures of vascular
function: PWV and FMD.
Small Artery Elasticity Index (SAE)
The HDI/PulseWave CR-2000 System (Hypertension
Diagnostics, Inc.) was used to measure SAE. A
noninvasive tonometer was applied to the skin above
the radial artery at the wrist. The tonometer provided
a pulse contour analysis of radial artery waveforms
and calculated SAE.
Twenty-five stable hemodialysis patients of were
studied. Subjects were evaluated for vascular function
with 3 methods: PWV, FMD and SAE. In addition,
arterial blood pressure and heart rate were measured.
Pulse Wave Velocity (PWV)
Carotid-femoral pulse wave velocity was measured
noninvasively with applanation tonometry (SphygmoCor Pulse Wave Velocity Vx System). In this method,
a probe was applied over the carotid and femoral
arteries to detect the arterial pressure wave. The
timing of pulse wave arrivals was used to calculate
PWV, which is high in stiff arteries.
Flow Mediated Dilatation (FMD)
A blood pressure cuff was inflated for 4 minutes
(causing ischemia) and then suddenly released,
causing an increase in blood flow and reactive
release of nitric oxide, an arterial vasodilator. The
diameter of the brachial artery was measured by
ultrasound before and after occlusion of the brachial
artery, and percentage increase in arterial diameter
was computed.
•
•
•
•
Measurements in this cohort of ESRD patients
were generally consistent with arterial stiffness
and dysfunction (high systolic and pulse
pressures, high PWV, low SAE, and low FMD).
Lower SAE was associated with higher PWV.
There was no correlation between SAE and FMD
Over 70% of SAE variation is explained by its
association with PWV, pulse pressure, body mass
index, and mean arterial pressure.
Discussion
Results
•
•
•
•
•
•
Figure 1: Lower SAE was associated with
higher PWV.
Simple Regression Analysis
SAE negatively correlated with PWV (R2 = 0.29,
P = 0.009)
SAE did not correlate with FMD (P = 0.81)
SAE negatively correlated with mean arterial
pressure (R2 = 0.242, P = 0.013).
SAE negatively correlated with systolic pressure
(R2 = 0.191, P = 0.029)
SAE positively correlated with body mass index
(R2 = 0.337, P = 0.002)
•
•
•
Multiple Regression Analysis
SAE correlated with PWV, pulse pressure, body
mass index, and mean arterial pressure (R2 =
0.701, all P <0.022)
This study supports the utility of small artery
elasticity index as a measure of arterial stiffness
and vascular function in ESRD. In both simple
and multiple regression analyses, SAE correlated
with various vascular indicators, including PWV,
systolic pressure, and mean arterial pressure.
While SAE did not correlate with FMD, FMD did
not correlate with any measures of vascular
function (data not shown). This suggests that
FMD may not be an optimal method of measuring
vascular health in ESRD.
An unexpected finding was the positive correlation
between body mass index (BMI) and SAE. A
previous study found the same relationship and
suggested it might be due to the improved
vascular function found at higher BMIs within the
non-obese range [15].
References
Table 1: Patient demographics and mean values for vascular
testing. Values are consistent with arterial dysfunction: high
systolic & pulse pressure, low SAE, high PWV, low FMD.
Figure 2: Lower SAE was associated with
higher systolic blood pressure.
Patient characteristics (n = 25)
Materials and Methods
Summary
Patient age (yrs)
46.68
Female (%)
8
African American (%)
92
Body mass index (kg/m2)
28.01
Diabetes Mellitus (%)
32
Cardiovascular disease (%)
52
Systolic blood pressure (mmHg)
144.12
Diastolic blood pressure (mmHg)
81.47
Mean arterial pressure (mmHg)
105.77
Pulse pressure (mmHg)
62.65
Small artery elasticity index
(ml/mmHg x100)
5.69
Pulse wave velocity (m/s)
9.49
Flow mediated dilatation (%)
6.18
1. London GM, Marchais SJ, Guerin AP, et al. "Arterial structure and function in end-stage
renal disease.” Nephrol Dial Transplant 17: 1713-1724, 2002.
2. Pannier B, Guerin AP, Marchais SJ, et al. "Arterial structure and function in end-stage
renal disease.” Art Res 1: 79-88, 2007.
3. USRDS. United States Renal Data System; Annual Data Report, 2010.
4. Blacher J, Guerin AP, Pannier B, et al. "Arterial calcifications, arterial stiffness, and
cardiovascular risk in end-stage renal disease.” Hypertension. 2001 Oct;38(4):938-42.
5. Briet M, Bozec E, Laurent S, et al. “Arterial stiffness and enlargement in mild-tomoderate chronic kidney disease.” Kidney Int 69: 350-357, 2006.
6. Ku YM, Kim YO, Kim JI, et al. “Ultrasonographic measurement of intima-media
thickness of radial artery in predialysis ureaemic patients: comparison with histological
examination.” Nephrol Dial Transplant 21: 715-720, 2006.
7. Glassock RJ, Pecoits-Filho R, Barberato SH. Left Ventricular Mass in Chronic Kidney
Disease and ESRD. Clin J Am Soc Nephrol 4: S79–S91, 2009
8. Henrich WL. Optimal Cardiovascular Therapy for Patients with ESRD over the Next
Several Years. Clin J Am Soc Nephrol 4: S106–S109, 2009
9. McCullough PA. “Coronary Artery Disease.” Clin J Am Soc Nephrol 2: 611-616, 2007.
10. Ritz E, Bommer J. “Cardiovascular Problems on Hemodialysis: Current Deficits and
Potential Improvement.” Clin J Am Soc Nephrol 4: S71–S78, 2009.
11. Kapuku GK, Harshfield GA, Davis HC, Treiber FA. “Early markers of cardiovascular
disease.” Vascul Pharmacol. 45(5):277-80, 2006.
12. Faulx MD, Wright AT, Hoit BD. “Detection of endothelial dysfunction with brachial artery
ultrasound scanning.” Am Heart J. 145(6):943-51, 2003.
13. Kheda MF, Brenner LE, Patel MJ, Wynn JJ, White JJ, Prisant LM, Paulson WD.
“Influence of arterial elasticity and vessel dilatation on arteriovenous fistula maturation:
a prospective cohort study.” Nephrol Dial Transplant 25: 525–531, 2010.
14. Wilson AM, O'Neal D, Nelson CL, Prior DL, Best JD, Jenkins AJ. “Comparison of arterial
assessments in low and high vascular disease risk groups.” Am J Hypertens. 17(4):28591, 2004.
15. Kals JP, Kampus M, Kals R, et al. "Arterial Elasticity Is Associated with Endothelial
Vasodilatory Function and Asymmetric Dimethylarginine Level in Healthy Subjects."
Scan J Clin Lab Inves 67.5: 536-44, 2007.
Acknowledgements
Figure 3: Higher SAE was associated with
higher body mass index (BMI).
I would like to thank Dr. White, Dr. Kapuku, and Dr. Paulson for
all of the help they have given me on this project. I also
appreciate all the hard work James Halbert has put into the
study. Finally, I would like to thank the GHSU Dean’s Summer
Research Fellowship Program for funding the research and
giving me the opportunity to pursue my interests this summer.