J Med Ultrasonics (2009) 36:129–135
DOI 10.1007/s10396-009-0217-3

ORIGINAL ARTICLE

Relationship between upper limb peripheral artery stiffness
using the radial artery and atherosclerotic parameters
Shuumarjav Uurtuya Æ Kazuhiko Kotani Æ Nobuyuki Taniguchi Æ
Hiroaki Matsunaga Æ Hiroshi Kanai Æ Hideyuki Hasegawa Æ Kazuomi Kario Æ
Shun Ishibashi Æ Kouichi Itoh

Received: 11 December 2008 / Accepted: 5 January 2009 / Published online: 18 July 2009
Ó The Japan Society of Ultrasonics in Medicine 2009

Abstract
Purpose A new method has been developed for evaluatingarterial stiffness using transcutaneous and high-frequency
ultrasound. There may be a difference in the clinical significance of peripheral arteries, such as the radial artery (amuscular property), and other medium/large-sized arteries(an elastic property). The aim of this study was to determine
the relationship between upper limb peripheral arterial
stiffness (ULPAS) using the new method for the radial arteryand atherosclerotic parameters in comparison with carotid
intima-media thickness (IMT) and cardio-ankle vascularindex (CAVI) in a healthy population and a diseased population with hypertension (HT) and diabetes mellitus (DM).
Methods Forty-four apparently healthy individuals (meanage = 26.3 years, men/women = 14/30), 45 patients withdrug-treated HT (mean age = 55.3 years, men/women =17/28), and 37 patients with drug-treated DM (mean

S. Uurtuya  K. Kotani (&)  N. Taniguchi  H. Matsunaga
Department of Clinical Laboratory Medicine,
Jichi Medical University, 3311-1 Yakushiji,
Shimotsuke, Tochigi 329-0498, Japane-mail: kazukotani@Jichi.ac.jp
H. Kanai  H. Hasegawa
Graduate School of Engineering, Tohoku University,
Sendai, JapanK. Kario
Department of Cardiology, Jichi Medical University,
Shimotsuke, Tochigi, Japan
S. Ishibashi
Department of Endocrinology, Jichi Medical University,
Shimotsuke, Tochigi, JapanK. ItohHitachi-Omiya Saiseikai Hospital, Ibaraki, Japanage = 55.2 years, men/women = 21/16) were investigated.
Body mass index, systolic blood pressure (SBP), diastolicblood pressure (DBP), CAVI, IMT, ultrasonographicallymeasured ULPAS, blood lipid/glucose-related parameters, andC-reactive protein (CRP) were all determined.
Results Among the healthy subjects, ULPAS showed asignificantly positive correlation with SBP and CRP.
ULPAS showed a different correlation pattern with atherosclerotic parameters from that of IMT and CAVI. The
HT subjects had significantly higher ULPAS levels thanthose with DM. In this diseased population, ULPAS showeda significant positive correlation with SBP and DBP, as well
as a significant negative correlation with glucose.
Conclusion These results suggest that ULPAS may provide new information in association with some atherosclerotic conditions as a unique index different from IMT
and CAVI.
Keywords Radial artery  Arterial stiffness  CAVI 
IMT  Hypertension  Diabetes mellitus

Introduction
Atherosclerosis is an underlying process in cardiovasculardisease (CVD), a major cause of mortality worldwide, and
it is important to detect atherosclerotic alteration in order tomanage CVD [1]. The International Atherosclerosis Society has pointed out that hypertension (HT) and diabetes
mellitus (DM) are major risk factors for CVD [2]. An
increase in arterial stiffness is one manifestation of theatherosclerotic changes associated with these risk factors.
In HT, shear stress and peripheral vascular resistance are
related to arterial stiffness [3]. In DM, hyperglycemia
induces both macro- and microvascular stiffness [4].

123

130

Among the various methodologies for evaluating theatherosclerotic state in clinical practice, cardio-ankle
vascular index (CAVI), measured from brachial and ankle
pulse waveforms, is reflective of arterial stiffness independent of blood pressure (BP) [5], and the clinical significance of CAVI in CVD has been recently established[6]. Carotid intima-media thickness (IMT), measured byultrasound, is a well-established atherosclerotic index
connected with arterial stiffness [7].
In addition to impairment of endothelial function [8], thecompositional characterization (e.g., lipid, blood clot,
fibrous and calcified tissue) of atherosclerotic sites isthought to be a significant aspect of evaluation of regionalelasticity/stiffness and plaque rupture [9, 10]. Recently, anoninvasive transcutaneous ultrasonic technology thatutilizes the ‘‘phased tracking method’’ was developed inorder to evaluate atherosclerotic formation based on thecompositional features of the artery wall [9–12]. Thismethod allows the detection of minute changes in the
thickness of the layers of the arterial wall by subtracting thedisplacements of two points set along an ultrasonic beamduring a single heartbeat. Arterial wall elasticity is derived
from the thickness changes and pulse pressure of each layer
divided by the ultrasonic beam. When we use a system
based on this technology, the elasticity distribution is seenas the mean elastic modulus [9]. This method has alreadybeen used for detecting regional changes in the arterial wall
[9] and to assess endothelial function in combination withthe flow-mediated dilation test [12]. Higher carotid artery
elasticity in smokers as compared with nonsmokers has
also been suggested [13]. Recently, a study on the application of this method to the carotid artery in DM patientshas shown elasticity levels to be related to such atherosclerotic parameters as BP, pulse wave velocity, and IMT[14].
The radial artery is an upper limb peripheral artery andis categorized as a small artery, so the clinical impact ofatherosclerotic manifestation in the radial artery (having a
muscular property) may differ from that of the carotid
artery (having an elastic property). There are, however, noradial-artery-related clinical data available for this method.
Furthermore, although endothelial dysfunction has been
implicated in the pathology of large- and medium-sizedarteries in HT and DM [15, 16], a smaller artery may show
a greater correlation with endothelium-dependent vasodilation than a larger-sized artery [17, 18]. Examination
using the radial artery is thus expected to more clearlyreflect endothelial function.
Measurements performed by Kanai et al. [9] with thismethodology were originally referred to as ‘‘elasticity.’’ In
the present report, while there may be only a slight difference from the original meaning, we decided to use theterm upper limb peripheral artery stiffness (ULPAS)

123

J Med Ultrasonics (2009) 36:129–135

instead of the term elasticity, because arterial stiffness
rather than elasticity is clinically used more frequently.
That is, a low elasticity (a high mean elastic module)means an increase in stiffness. Therefore, the present study
has two aims: (1) to determine the relationships between
ULPAS and atherosclerotic parameters in comparison with
IMT and CAVI in an apparently healthy population, and(2) to evaluate ULPAS levels in subjects with HT and DM.

Subjects and methods
Two populations were used in this study. A total of 44
individuals who were apparently healthy, drug free, andnonsmokers were enrolled in this study as a healthy population [mean age = 26.3 ± 12.7 (standard deviation, SD)
years, men/women = 14/30]. Next, 45 patients treatedfor HT alone (mean age = 55.3 ± 9.4 years, men/
women = 17/28) and 37 patients treated for DM alone(mean age = 55.2 ± 9.6 years, men/women = 21/16)
were enrolled as a diseased population. This study wasapproved by the Ethical Committee of Jichi Medical University and each subject gave his or her informed consent.
The healthy population was composed of drug-free
nonsmokers from the general population who volunteered
to take part in the present study based on our random
invitation to participate in the study. The volunteers wereenrolled if they met the following laboratory criteria: bodymass index (BMI) of 18.5–24.9 kg/m2 [19], systolic BP(SBP) \140 mmHg, diastolic BP (DBP) \90 mmHg [20],fasting blood total cholesterol (TC) \220 mg/dL, triglyceride (TG) \150 mg/dL [21], and glucose \126 mg/dL[22]. After 48 subjects were consecutively screened, 4subjects were excluded because they did not meet theinclusion criteria. Next, patients who had all been referred
to Jichi Medical University Hospital were consecutively
recruited for the diseased population. HT subjects werelimited to those treated with drugs such as angiotensinconverting enzyme inhibitors (ACEI) and angiotensin
receptor blockers (ARB), which may affect arterial stiffness [23, 24]. DM subjects were limited to those treatedwith drugs such as sulfonylurea and insulin, which have notbeen suggested to affect the stiffness. Information on theprescribed drugs was confirmed by professional interviews
and medical records. HT and DM subjects were alreadydiagnosed, respectively, and no patients with both HT and
DM were included in this study. In both the healthy anddiseased population, no subjects had any known history of
CVD, kidney disease or liver disease.
Smoking habits were confirmed through professional
interviews, and smokers were defined as current smokers.
BMI was calculated as weight divided by the square ofbody height while wearing light clothes. Blood samples

J Med Ultrasonics (2009) 36:129–135

were collected from the antecubital vein after a 12-hovernight fast without drugs. Serum TC, high-density
lipoprotein cholesterol (HDL-C), TG, and plasma glucose
were measured by enzymatic methods using an automatic
analyzer (Hitachi Co., Ltd., Tokyo, Japan). Low-density
lipoprotein cholesterol (LDL-C) was determined by thefollowing equation: TC - (HDL-C) - (TG/5) [25]. SerumCRP was measured using a latex agglutination immune
assay (EIKEN Chemical, Co., Ltd., Tokyo, Japan). Plasma
insulin was measured by a sandwich enzyme immunoassay(TOSOH Co., Ltd., Tokyo, Japan). Homeostasis model
assessment-insulin resistance (HOMA-IR) was calculatedby the following formula: (fasting plasma insulin concentration 9 fasting glucose concentration)/405 [26].
CAVI was determined by oscillometric technology
using the VaSera VS-1000 vascular screening system(Fukuda Denshi Co., Ltd., Tokyo, Japan) [5]. CAVI isbased on the stiffness parameter calculated using the following formula: CAVI = ln(Ps/Pd) 9 2q/DP 9 PWV2
(Ps: SBP, Pd: DBP, q: blood density, DP: pulse pressure,
PWV: pulse wave velocity between the aortic and the ankle
value). Subjects lay on a bed in a supine position for
10 min before the measurements. SBP and DBP were
measured simultaneously. After 5 min of relaxing in thesupine position, IMT of the bilateral common carotid
arteries was measured by ultrasonography with a 10-MHz
probe using the EH54-9DR system (DIASUS, Scotland,
UK). IMT levels were determined by the average of thevalues at points 1, 2, and 3 cm below carotid bifurcation oneach side of the artery.
Subsequently, in the same supine position, ULPAS was
examined in the right arm based on the previously documented method [9]. In brief, ULPAS was scanned 5 cm
above the right wrist, with the palm turned upward. The
transducer (8–16 MHz probe) was oriented in a direction
perpendicular to the longitudinal axis of the radial artery.
The arterial wall was divided into multiple layers by theultrasound beams. The mean elastic modulus wascomprehensively computed in the scanned regions of thearterial wall. The values of the modulus were then automatically calculated after displaying them as color-coded
images with histograms. With respect to the elasticity
distribution, if lipid (cholesterol)-rich components in theartery were captured, then the ULPAS values could generally be low, while in other cases, the values could behigher.

Statistical analysis
Data are presented as mean ± standard deviation. In thecase of parameters with nonparametric distributions (BMI,
DBP, IMT, CAVI, TC, LDL-C, TG, insulin, HOMA-IR,

131

CRP, and ULPAS), data are shown as median (interquartile
range). In all analyses, the parameters with nonparametric
distributions were used after log transformation. Categorical data were compared between the groups by v2 test, andcontinuous data were compared by unpaired t test (in acomparison between HT and DM subjects, age, gender, andsmoking habit were adjusted). To investigate the correlations of IMT, CAVI, and ULPAS with other atherosclerotic
parameters, Pearson’s correlation and a partial correlation
test with adjustments for age and gender were used. All
statistical analyses were performed by the Statistical
Package for Social Science (SPSS) version 16.0 (SPSS
Inc., Chicago, IL) for Windows. A p value of \0.05 wasconsidered to be statistically significant.

Results
The characteristics of subjects in the healthy population are
shown in Table 1. BMI and IMT levels were significantly
higher and HDL-C, insulin, and HOMA-IR levels weresignificantly lower in men as compared with women. Other
atherosclerotic parameters, including CAVI and ULPAS,
did not show any significant differences between thegenders.
The relationships between IMT, CAVI, ULPAS, andother atherosclerotic parameters in the healthy population
are shown in Table 2 (a simple correlation test between bivariables) and Table 3 (a correlation test with adjustments
for age and gender). According to the simple correlation
test, carotid IMT levels demonstrated a significantly positive correlation with male gender (Table 2), but age- andgender-adjusted correlation tests did not show any relative
significance (Table 3). Similarly, in the simple correlation
test, CAVI was significantly positively correlated with age,
DBP, TC, LDL-C, and CRP, but in the age- and genderadjusted correlation tests, the significance of these correlations disappeared. ULPAS was significantly positively
correlated with SBP and CRP in the simple correlation test,
and ULPAS remained significantly positively correlatedwith SBP and CRP in the adjustment correlation tests.
Furthermore, regarding the relationships between IMT,CAVI, and ULPAS, in a simple correlation test, ULPAS
tended to be correlated with IMT (r = 0.28, p = 0.07) or
CAVI (r = 0.26, p = 0.09) but did not reach a statsisticalsignificance, and there was no correlation between CAVI
and IMT (r = 0.21, p = 0.17). Similarly, in the age- andgender-adjusted correlation tests, ULPAS was not significantly correlated with IMT (r = 0.19, p = 0.36) or CAVI
(r = 0.19, p = 0.26), respectively. CAVI was not significantly correlated with IMT (r = 0.0001, p = 0.99).
The comparative characteristics between HT and DM
subjects are shown in Table 4. The number of subjects with

123

132

J Med Ultrasonics (2009) 36:129–135

Table 1 Clinical characteristics in an apparently healthy population
All (n = 44)

Men (n = 14)

Women (n = 30)

Age (years)

26.3 ± 12.7

23.9 ± 7.9

25.5 ± 10.5

BMI (kg/m2)

21.2 ± 1.6

21.9 ± 1.3

20.9 ± 1.6*

HR (bpm)

60.0 ± 10.2

56.7 ± 7.3

61.5 ± 11.2

SBP (mmHg)

111.6 ± 9.2

115.1 ± 9.0

109.9 ± 9.1

DBP (mmHg)

66.0 [63.3–71.5]

66.0 [63.5–69.0]

66.0 [64.0–74.0]
179.5 ± 23.4

TC (mg/dL)

178.2 ± 24.0

175.5 ± 25.8

LDL-C (mg/dL)

97.5 [86.0–116.8]

100.5 [89.0–116.5]

93.5 [84.8–117.3]

HDL-C (mg/dL)

63.8 ± 10.7

58.6 ± 8.7

66.2 ± 10.8*

TG (mg/dL)

68.1 [44.8–86.8]

78.5 [49.0–87.6]

60.1 [44.8–84.6]

Glucose (mg/dL)

88.0 [83.0–97.5]

88.0 [84.5–98.0]

87.5 [82.0–94.5]

Insulin (lm/L)
HOMA-IR5.6 ± 3.1
1.24 ± 0.69

4.2 ± 2.0
0.94 ± 0.47

6.3 ± 3.4*
1.38 ± 0.74*

CRP (mg/dL)

0.05 [0.02–0.07]

0.05 [0.01–0.07]

0.05 [0.03–0.07]

IMT (mm)0.41 [0.37–0.46]

0.45 [0.43–0.50]

0.40 [0.37–0.44]*

CAVI

5.71 [5.29–6.04]

5.84 [5.33–6.38]

5.69 [5.27–6.04]

ULPAS (kPa)

231.4 [179.4–295.6]

262.2 [178.5–326.7]

223.3 [178.0–268.7]

Age, HR, HDL-C, and glucose are presented as mean ± standard deviation. Other parameters are presented as median [interquartile range]
BMI body mass index, HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure, IMT intima-media thickness, CAVI cardio-ankle
vascular index, ULPAS upper limb peripheral arterial stiffness, TC total cholesterol, HDL-C high-density lipoprotein cholesterol, LDL-C lowdensity lipoprotein cholesterol, TG triglyceride, HOMA-IR homeostasis model assessment-insulin resistance, CRP C-reactive protein
Significance level (men versus women; unpaired t test): *p \ 0.05

ACEI was 6 (13.3%) and that of ARB was 39 (86.7%),
respectively. The number of subjects with sulfonylurea was
19 (51.3%), with insulin was 7 (18.9%), and with sulfonylurea plus insulin was 11 (29.8%), respectively.
Although HT subjects had significantly lower levels of
glucose and HOMA-IR than did DM subjects, HT subjects
showed significantly higher ULPAS levels in addition to
SBP and DBP levels as compared with DM subjects.
In the case of a combination of HT and DM subjects, ina simple correlation test, ULPAS was significantly positively correlated with SBP (r = 0.54, p = 0.001) and DBP(r = 0.34, p = 0.002), and significantly negatively correlated with glucose (r = -0.23, p = 0.04). In the age- andgender-adjusted correlation test for ULPAS, the following
correlations only remained significant: with SBP (r = 0.53,
p = 0.001) and DBP (r = 0.34, p = 0.002). In similar
analyses, IMT and CAVI did not show significant correlations with SBP, DBP, and glucose, respectively.

Discussion
The present study is the first to investigate the stiffness ofthe ‘‘radial artery’’ using high-frequency transcutaneous
ultrasound with an innovative ‘‘phased tracking method’’.
Measurement of ULPAS was feasible in a clinical setting.
ULPAS levels were significantly positively correlated with123

SBP and CRP levels in an apparently healthy population.
ULPAS did not show a similar correlation pattern with thatof IMT and CAVI, and it did not show any correlation with
IMT or CAVI, respectively. Moreover, HT subjects had ahigher ULPAS level than DM subjects in this study, andULPAS levels were significantly positively correlated withBP levels. These results suggest that ULPAS may offer
information in association with some atherosclerotic conditions with the possibility of a unique index different from
IMT and CAVI.
Accumulating evidence has indicated that a slightincrease in serum CRP level is a risk parameter of atherosclerosis, even in healthy subjects [27–29]. CRP is
considered to interact with the vascular state, especially theendothelium, as a proinflammatory marker. Specifically,
CRP promotes potential atherogenesis by inducing monocyte-macrophage activation, tissue factor expression, therelease of other procoagulant cytokines, the downregulation of atheroprotective molecules (such as endothelial
nitric oxide (NO) and transforming growth factor b-1), etc.
[28–30]. The radial artery is an artery with a muscle
property, and even a normal range of CRP in vascularsmooth muscle cells can induce the increases in several
inflammatory molecules within the cell [31]. In addition,
the alteration of endothelial NO is reportedly sensitive in asmall artery in a healthy population [32]. On the other
hand, although there was a prior report showing a weakJ Med Ultrasonics (2009) 36:129–135

133

Table 2 Relationships between the respective arterial stiffness
markers and atherosclerotic parameters in an apparently healthy
population
IMT

CAVI

Table 3 Age- and gender-adjusted relationships between therespective arterial stiffness markers and atherosclerotic parameters in
an apparently healthy population

ULPAS

IMT

CAVI

ULPAS

Age (years)

0.28 (0.07)

0.69 (\0.0001)**

0.21 (0.17)

BMI (kg/m2)-0.10 (0.52)-0.15 (0.23)

0.16 (0.33)

Gender (men)0.32 (0.04)*

0.01 (0.96)

0.18 (0.24)

HR (bpm)

0.10 (0.50)-0.02 (0.88)

0.09 (0.57)

BMI (kg/m2)

0.10 (0.50)

0.08 (0.63)

0.25 (0.10)

HR (bpm)

0.07 (0.64)

0.10 (0.53)

0.08 (0.60)

SBP (mmHg)
DBP (mmHg)

0.06 (0.71)
0.03 (0.84)

0.09 (0.49)
0.08 (0.52)

0.37 (0.02)*
0.13 (0.46)

SBP (mmHg)

0.23 (0.14)

0.29 (0.06)

0.43 (0.004)**

TC (mg/dL)

0.12 (0.45)

0.04 (0.76)-0.13 (0.46)

DBP (mmHg)

0.11 (0.49)

0.38 (0.01)*

0.17 (0.28)

LDL-C (mg/dL)

0.04 (0.80)

0.05 (0.68)-0.14 (0.39)

TC (mg/dL)

0.22 (0.15)

0.35 (0.01)*-0.01 (0.99)

HDL-C (mg/dL)

0.27 (0.07)-0.05 (0.68)

0.08 (0.61)

LDL-C (mg/dL)

0.18 (0.24)

0.32 (0.04)*-0.02 (0.90)

TG (mg/dL)-0.22 (0.14)

0.02 (0.86)-0.25 (0.12)

HDL-C (mg/dL)

0.14 (0.35)-0.03 (0.87)

0.02 (0.90)

Glucose (mg/dL)

0.11 (0.50)-0.13 (0.32)-0.07 (0.69)-0.08 (0.59)

0.22 (0.15)-0.14 (0.35)

Insulin (lm/mL)-0.03 (0.85)

0.02 (0.84)

0.24 (0.13)

0.26 (0.09)

0.21(0.18)

0.07 (0.66)

HOMA-IR-0.01 (0.94)

0.001 (1.00)

0.22 (0.17)

Insulin (lm/mL) -0.11 (0.46)

0.05 (0.76)

0.17 (0.28)

CRP (mg/dL)-0.03 (0.86)

0.12 (0.31)

0.32 (0.04)*

HOMA-IR-0.07 (0.66)

0.07 (0.65)

0.17 (0.27)

CRP (mg/dL)

0.06 (0.68)

0.33 (0.03)*

0.36 (0.02)*

The correlation was analyzed with adjustment for age and gender.
BMI, SBP, DBP, IMT, CAVI, ULPAS, TC, LDL-C, TG, insulin,
HOMA-IR, and CRP were log-transformed

TG (mg/dL)
Glucose (mg/dL)

Data are all presented as r (p value). HR, DBP, IMT, CAVI, ULPAS, TC,
TG, glucose, insulin, HOMA-IR, and CRP were log-transformed
BMI body mass index, HR heart rate, SBP systolic blood pressure, DBP
diastolic blood pressure, IMT intima-media thickness, CAVI cardioankle vascular index, ULPAS upper limb peripheral arterial stiffness,
TC total cholesterol, HDL-C high-density lipoprotein cholesterol,
LDL-C low-density lipoprotein cholesterol, TG triglyceride, HOMA-IR
homeostasis model assessment-insulin resistance, CRP C-reactive
proteinSignificance level (Pearson’s correlation test): *p \ 0.05, **p \ 0.001

correlation between CRP and radial artery stiffness using theoscillometric method in an older population [33], the method
used and the population could affect the results between
studies. Also, our result of the significant correlation between
SBP and ULPAS might be partly explained by the following
knowledge. The small artery is regarded as an important key
in the increased resistance of peripheral artery, leading toelevated BP [34]. The impaired NO on peripheral bloodvessels in the hypertensive state is well-documented [35].
Accordingly, as claimed previously, the radial artery (as usedin the ULPAS measurements), rather than larger arteries, issuitable for examining the vascular state including endothelial function and that evaluation of peripheral arterial stiffness can thus result in an early diagnosis of atherosclerotic
processes [17, 18, 36]. Taken together, these findings may
support the results that indicate that ULPAS is more obviously correlated to SBP and CRP than to IMT and CAVI.
Given that the measure of ULPAS is still quite new, further
studies are necessary to establish the associations between
ULPAS and atherosclerotic parameters.
In our healthy population, comparisons between IMT,CAVI, and ULPAS indicated a different correlation patternfrom atherosclerotic parameters and no interaction witheach other. These results are likely compatible with an earlier

BMI body mass index, HR heart rate, SBP systolic blood pressure,
DBP diastolic blood pressure, IMT intima-media thickness, CAVI
cardio-ankle vascular index, ULPAS upper limb peripheral arterial
stiffness, TC total cholesterol, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, TG triglyceride,
HOMA-IR homeostasis model assessment-insulin resistance, CRP Creactive protein
Significance**p \ 0.001

level(Pearson’s

correlationtest):*p \ 0.05,

work [13]. This may not be surprising, because IMT and
CAVI do not necessarily yield qualitative information
regarding regional elasticity. On the other hand, although our
results are relatively different from other earlier results using
a similar method on the carotid artery in DM patients [14],differences in the kinds of arteries and study populations
could explain the differences. The current results suggest thatULPAS may represent a unique feature in an upper peripheral artery that cannot be evaluated by CAVI and IMT
measurements. Further clinical application of ULPAS measurement would establish the specific usefulness of ULPAS.
In the present study, HT subjects were all treated withACEI or ARB, which can improve arterial stiffness [23, 24].
Even under these conditions, higher ULPAS levels wereobserved in our HT subjects. To date, there have been nocomparative data on arterial stiffness, regardless of arterial
size, between HT and DM. HT patients generally haveelevated peripheral vascular tone and resistance [3, 34, 37,38]. DM patients experience worsening enhancement ofvarious metabolic inflammatory and hemostatic changes,
accompanied by dysglycemia, thus resulting in vasculardamage [4, 39]. Our study also found ULPAS to correlatewith BP positively and glucose negatively. In addition,
while the study setting was different from ours, BP has been

123

134

J Med Ultrasonics (2009) 36:129–135

Table 4 Comparison of atherosclerotic parameters between HT and DM subjects
All (n = 82)

HT (n = 45)

DM (n = 37)
55.2 ± 9.6

Age (years)

55.3 ± 9.4

55.3 ± 9.4

Gender, men (%)

46.3

37.8

56.8

Smoking (%)

17.1

13.3

21.6

BMI (kg/m2)

23.9 [21.8–26.4]

24.1 [22.4–26.7]

23.5 [20.7–26.3]

HR (bpm)

65.2 ± 10.1

63.2 ± 9.3

67.7 ± 10.7

SBP (mmHg)

130.9 ± 14.1

134.9 ± 15.0

126.0 ± 11.5*

DBP (mmHg)

82.3 ± 10.2

85.9 ± 10.2

78.0 ± 8.6**

TC (mg/dL)

195.7 ± 36.8

197.8 ± 34.6

193.2 ± 39.7

LDL-C (mg/dL)

114.4 ± 28.7

115.4 ± 28.6

113.0 ± 29.6

HDL-C (mg/dL)

57.7 [45.0–65.0]

61.0 [52.5–66.3]

50.0 [42.0–61.0]

TG (mg/dL)
Glucose (mg/dL)

100.7 [71.8–136.8]
111.5 [93.0–152.8]

102.0 [64.0–118.0]
95.0 [89.0–106.5]

99.0 [78.5–153.5]
155.0 [130.0–202.5]**

Insulin (lm/L)

6.0 [4.0–9.8]

5.7 [4.1–8.1]

7.2 [3.3–11.8]

HOMA-IR

1.8 [1.0–2.9]

1.3 [0.9–2.1]

2.5 [1.2–5.2]**

CRP (mg/dL)

0.05 [0.03–0.11]

0.05 [0.03–0.10]

0.05 [0.03–0.16]

IMT (mm)

0.63 [0.55–0.77]

0.60 [0.54–0.70]

0.70 [0.58–0.83]

CAVI

8.00 ± 1.04

7.84 ± 0.97

8.20 ± 1.11

ULPAS (kPa)

441.5 ± 199.9

485.9 ± 200.6

387.7 ± 188.0*

Age, HR, DBP, ULPAS, TC, and LDL-C are presented as mean ± standard deviation. Other parameters are presented as median [interquartile
range]. A comparative test (except for age, gender, and smoking) was performed with adjustments for age, gender, and smoking. BMI, SBP,
CAVI, IMT, HDL-C, TG, glucose, insulin, HOMA-IR, and CRP were log-transformed
HT hypertension, DM diabetes mellitus, BMI body mass index, HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure, IMT
intima-media thickness, CAVI cardio-ankle vascular index, ULPAS upper limb peripheral arterial stiffness, TC total cholesterol, HDL-C highdensity lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, TG triglyceride, HOMA-IR homeostasis model assessment-insulin
resistance, CRP C-reactive protein
Significance level (unpaired t test or v2 test: HT versus DM): *p \ 0.05, **p \ 0.001

reported to be a more important determinant of carotid
artery stiffness (measured by the same method as ours) thanDM (glucose)-related parameters [14]. Given these data,
whereas it is possible that HT subjects may show a higher
peripheral arterial stiffness than DM subjects, it may beplausible that the BP levels are associated with ULPAS in
the diseased state. Further comparisons between ULPAS
and the pathologies of HT and DM are thus called for.
There were some limitations to this study. The study
sample size was small, which may limit the strength of theconclusions. The cross-sectional approach did not yield any
data on causality. In this diseased population with HT andDM, the duration and severity of the disease was not fully
examined. Finally, the technique for determining ULPAS
is dependent on the ultrasound probe position on the skin.
Although we obtained ULPAS data for the left arm, it was
sometimes difficult to set the probe on the side, probably
because the operator was right-handed. Therefore, ULPAS
data for the right arm were used in this study. Moreover,technical differences regarding the size of measured
arteries are considered to be an interesting topic to beaddressed in future studies.

123

Conclusions
The present study results suggest that, as a unique index
different from IMT and CAVI, ULPAS may provide new
information for evaluating upper peripheral arteries inassociation with some atherosclerotic conditions, as presented in CRP and SBP in a healthy population, and BP ina diseased population with HT and DM. Further studies areneeded to establish the clinical significance of ULPAS inatherosclerotic diseases.
Acknowledgments The present study was supported in part by agrant-in-aid from the Japanese Society of Laboratory Medicine Fundfor the Promotion of Scientific Research, Japan.

References
1. World Health Organization. Preventing chronic disease: a vital
investment. Geneva: WHO; 2005.
2. Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR. Non-insulin
dependent diabetes mellitus and fasting glucose and insulin
concentrations are associated with arterial stiffness indexes: theARIC study. Circulation. 1995;91:1432–43.

J Med Ultrasonics (2009) 36:129–135
3. Lund-Johansson P. Haemodynamics in essential hypertension.
Clin Sci. 1980;59:343–54.
4. Hsueh WA, Anderson PW. Hypertension, the endothelial cell,and the vascular complications of diabetes mellitus. Hypertension. 1992;20:253–63.
5. Shirai K, Utino J, Otsuka K, Masanobu T. A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle
vascular index (CAVI). J Atheroscler Thromb. 2006;13:101–7.
6. Nakamura K, Tomaru T, Yamamura S, et al. Cardio-ankle vascular index is a candidate predictor of coronary atherosclerosis.
Circ J. 2008;72:598–604.
7. Staub D, Meyerhans A, Bundi B, et al. Prediction of cardiovascular morbidity and mortality: comparison of the internal carotid
artery resistive index with the common carotid artery intimamedia thickness. Stroke. 2006;37:800–5.
8. Dierk H, Schiffrin Ernesto L. Endothelial dysfunction. J Am Soc
Nephrol. 2004;15:1983–92.
9. Kanai K, Hasegawa H, Ichiki M, et al. Elasticity imaging ofatheroma with transcutaneous ultrasound. Circulation. 2003;107:
3018–20.
10. Tsuzuki K, Hasegawa H, Ichiki M, Tezuka F, Kanai H. Optimal
region-of-interest settings for tissue characterization based on
ultrasonic elasticity imaging. Ultrasound Med Biol. 2008;34:573–
85.
11. Hasegawa H, Kanai H, Ichiki M, Tezuka F. Tissue structure ofarterial wall revealed with elasticity imaging. J Med Ultrason.
2007;34:73–4.
12. Ikeshita K, Hasegawa H, Kanai H. Ultrasonic measurement oftransient change in stress–strain property of radial arterial wallcaused by endothelium-dependent vasodilation. Jpn J Appl Phys.
2008;47:4165–9.
13. Yamagishi T, Kato M, Koiwa Y, Hasegawa H, Kanai H. Usefulness of measurement of carotid arterial elasticity distribution
in detection of early-stage atherosclerotic lesions caused by cigarette smoking. J Med Ultrason. 2006;33:203–10.
14. Okimoto H, Ishigaki Y, Koiwa Y, et al. A novel method forevaluating human carotid artery elasticity: possible detection ofearly stage atherosclerosis in subjects with type 2 diabetes.
Atherosclerosis. 2008;196:391–7.
15. Taddie S, Virdus A, Mattei P, et al. Defective L-arginine-nitricoxide pathway in offspring of essential hypertensive patients.
Circulation. 1996;94:1298–303.
16. Rizzoni D, Porteri E, Guelfi D, et al. Structural alterations in
subcutaneous small arteries of normotensive and hypertensive
patients with non-insulin-dependent diabetes mellitus. Circulation. 2001;103:1238–44.
17. Tao J, Tu C, Wang Y, et al. Impaired endothelium-dependent
vasodilation and arterial elasticity in patients with coronary arterydisease. J Allergy Clin Immunol. 2005;33:150–2.
18. Kaneko T, Hasegawa H, Kanai H. Ultrasonic measurement ofchange in elasticity due to endothelium dependent relaxation
response by accurate detection of artery-wall boundary. Jpn J
Appl Phys. 2007;46:4881–8.
19. WHO expert consultation. Appropriate body-mass index for
Asian populations and its implications for policy and intervention
strategies Lancet 2004;363:157–63.
20. Chalmers J. Classification of hypertension according to WHO/
ISH. J Hypertens. 1999;17:151–85.
21. Hata Y, Mabuchi H, Saito Y, et al. Report of the Japan atherosclerosis society (JAS) guideline for diagnosis and treatment of

135
hyperlipidemia in Japanese adults. J Atheroscler Thromb.
2002;9:1–27.
22. American Diabetes Association. Diagnosis and classification ofdiabetes mellitus. Diabetes Care. 2004;27:S5–10.
23. Agabiti-Rosie E. Structural and functional changes of the
microcirculation in hypertension: influence of pharmacologicaltherapy. Drugs. 2003;63:19–29.
24. Hata M, Sezai A, Niino T, et al. Vascular protecting effect ofangiotensin receptor blocker (ARB) on the radial artery graft.
Ann Thorac Cardiovasc Surg. 2008;14:25–8.
25. Friedwald WT, Levy RJ, Fredrickson D. Estimation of the concentration of low-density lipoprotein cholesterol in plasma,
without use of the preparative ultracentrifuge. Clin Chem.
1972;18:499–502.
26. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis
model assessment: insulin resistance and beta-cell function fromfasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.
27. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation,
aspirin, and the risk of cardiovascular disease in apparently
healthy men. N Engl J Med. 1997;336:973–9.
28. Ferri C, Croce G, Cofini V, Berardinis GD, Grassi D, Casale R,
et al. C-reactive protein: interaction with the vascular endothelium and possible role in human atherosclerosis. Curr Pharm Des.
2007;13:1631–45.
29. Venugopal SK, Devaraj S, Jialal I. Effect of C-reactive protein on
vascular cells: evidence for a proinflammatory, proatherogenicrole. Curr Opin Nephrol Hypertens. 2005;14:33–7.
30. Ikonomidis I, Stamatelopoulos K, Lekakis J, Vamvakou GD,
Kremastinos DT. Inflammatory and non-invasive vascularmarkers: the multimarker approach for risk stratification in coronary artery disease. Atherosclerosis. 2008;199:3–11.
31. Hattori Y, Matsumura M, Kasai K. Vascular smooth muscle cell
activation by C-reactive protein. Cardiovasc Res. 2003;58:186–95.
32. McVeign GE, Allen PB, Morgan DR, Hanratty CG, Silke B.
Nitric oxide modulation of blood vessel tone identified by arterial
waveform analysis. Clin Sci. 2001;100:387–93.
33. Duprez DA, Somasundaram PE, Sigurdsson G, Hoke L, Florea N,
Cohn JN. Relationship between C-reactive protein and arterial
stiffness in an asymptomatic population. J Hum Hypertens.
2005;19:515–9.
34. Schiffrin EL. Reactivity of small blood vessels in hypertension:
relation with structural changes. State of the art lecture. Hypertension 1992;19:SII 1–9
35. Spieker LE, Flammer AJ, Lüscher TF. The vascular endothelium
in hypertension. Handb Exp Pharmacol 2006;(176):249–283
36. Agewall S, Douhty RN, Bagg W, Whalley GA, Braatvendt G,
Sharpe N. Comparison of ultrasound assessment of flow-mediated dilation in the radial and brachial artery with upper andforearm cut positions. Clin Physiol. 2001;21:9–14.
37. Aalkaer C, Heagerty AM, Peterson KK, et al. Evidence forincreased media thickness, increased neuronal amine uptake anddecreased excitation-contraction coupling in isolated resistancevessels from essential hypertensives. Circ Res. 1987;61:181–6.
38. Stephens N, Heagerty AM. The sympathetic nervous system andsmall artery neuroeffector function in hypertension. Vase Med
Review. 1994;5:75–93.
39. Cameron JD, Cruickshank JK. Glucose, insulin, diabetes andmechanisms of arterial dysfunction. Clin Exp Pharmacol Physiol.
2007;34:677–82.

123