Atherosclerosis 206 (2009) 168–172

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Atherosclerosis
journal homepage: www.elsevier.com/locate/atherosclerosis

Carotid arterial elasticity is a sensitive atherosclerosis value reﬂecting visceralfat accumulation in obese subjects
Ai Tokita a , Yasushi Ishigaki a , Hisashi Okimoto a , Hideyuki Hasegawa c , Yoshiro Koiwa d ,Makoto Kato e , Hisamitsu Ishihara a , Yoshinori Hinokio a , Hideki Katagiri b ,Hiroshi Kanai c , Yoshitomo Oka a,∗aDivision of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
Division of Advanced Therapeutics for Metabolic Diseases, Tohoku University Graduate School of Medicine, Japanc
Department of Electrical Engineering, Tohoku University Graduate School of Engineering, Tohoku University, Sendai, Japand
Oizumi Memorial Hospital, Shiroishi, Japane
Panasonic Shikoku Electronics Co., Ltd., Yokohama, Japanba r t i c l e

i n f oArticle history:
Received 30 August 2008
Received in revised form 29 January 2009
Accepted 30 January 2009
Available online 20 February 2009
Keywords:
Elasticity
Obesity
UltrasoundVisceral adiposity
Early stage atherosclerosisa b s t r a c t
Background: We previously reported the arterial elasticity value we measured to reﬂect the characteristicfeatures of vessel walls, and to possibly be useful for detecting early stage atherosclerosis in type 2
diabetes. Obesity, especially visceral adiposity, is well known to play a crucial role in the development of
metabolic disorders and atherosclerosis. To assess whether arterial elasticity value reﬂects the effect ofobesity on atherosclerosis, we examined the associations of obesity characteristics with atherosclerosis
values including arterial elasticity, carotid intima–media thickness (IMT) and pulse wave velocity (PWV).
Methods: Three atherosclerosis values were measured in 78 obese subjects (body mass index ≥30).
We investigated the associations of atherosclerosis values with obesity-related parameters including
abdominal fat accumulation determined by computed tomography.
Results: Arterial elasticity values were positively related to established atherosclerosis values, carotid IMT
and PWV, in obese subjects. Age, systolic blood pressure and hypertension also correlated with theseatherosclerosis values. Single regression analysis showed all three atherosclerosis values to correlatesigniﬁcantly with visceral fat area. Intriguingly, visceral fat area is an independent variable affecting
arterial elasticity, but not IMT or PWV. Furthermore, multiple regression analysis revealed that arterial
elasticity correlates strongly with visceral fat area.
Conclusions: Arterial elasticity value we measure is a new parameter for evaluating atherosclerosis insubjects with visceral adiposity and more sensitive than the currently established atherosclerosis values,
carotid IMT and PWV. Measuring arterial elasticity has the potential to reveal minute vascular changes,
and may have broad clinical applications for evaluating early stage atherosclerosis.
© 2009 Elsevier Ireland Ltd. All rights reserved.

Obesity has increased dramatically, becoming a global epidemic in recent decades [1]. Obesity is closely associated withthe development of atherosclerosis [2], via rising incidences ofmetabolic disorders, including diabetes, dyslipidemia, hypertension, inﬂammation, and the prothrombotic state [3]. Furthermore,obesity is involved in sympathetic nerve activation as well as cardiac structural and functional adaptations [4], and is reportedly
an independent cardiovascular risk factor [5]. Recent studies haveshown that adipocytokines, such as PAI-1, TNF-␣ and adiponectin,
play crucial roles in the development of metabolic disorders and∗ Corresponding author. Tel.: +81 22 717 7611; fax: +81 22 717 7611.
E-mail address: oka-y@mail.tains.tohoku.ac.jp (Y. Oka).
0021-9150/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2009.01.046

atherosclerosis, in various tissues including the vasculature [6]. In
particular, visceral fat accumulation, rather than the body massindex (BMI) or subcutaneous fat accumulation, was shown to bestrongly associated with various obesity-related disorders [7], andis thus considered to be a major risk factor for cardiovascular disease [8]. Many studies have shown that increasing body weight isclosely related to the surrogate markers associated with atherosclerosis, such as carotid intima–media thickness (IMT) and pulse
wave velocity (PWV). In addition, visceral adiposity is reportedly
related to atherosclerosis, which is determined by carotid IMT[9–13], coronary calciﬁcation [14] and arterial stiffness [15,16]. In
some reports, this relationship persisted after adjustments for multiple linear regression analysis [12–15]. While visceral fat areas
were correctly measured by computed tomography (CT) scans infew studies [12,15], abdominal ultrasound was employed in many

A. Tokita et al. / Atherosclerosis 206 (2009) 168–172

reports [9–11,13,14,16], which is often imprecise to determine visceral fat area. It has been widely recognized that non-invasive
methods of evaluating atherosclerosis have limitations, such as
slow changes in carotid IMT and the inﬂuence of blood pressure on PWV. Thus, an accurate and practical means of evaluating
atherosclerosis is needed.
Recently, we developed a novel non-invasive method for measuring a change in thickness of multiple layers preset in arterial
wall during a single heartbeat [17,18]. Brieﬂy, multiple points were
preset from the luminal surface to the adventitia of the posterior wall along an ultrasonic beam and the displacements atthese preset points were estimated by applying the phased tracking method to the received echo. A layer was deﬁned as being
between two points. A minute change in thickness of the layer
was obtained by subtraction of the displacements at these twopoints and then, the strain of the layer was obtained by dividing
the change in thickness by the original thickness set at the end
diastole. By changing the depth and applying the same procedure,
the strains at multiple depths in arterial wall were obtained atconstant intervals, usually 80 ␮m. This innovative phased tracking method enables us to evaluate regional characteristics of theartery in detail; during a single heartbeat these sites either deform
easily in soft regions or there is little deformation in hard regions.
We integrated changes in thickness, which we describe with theterm “arterial elasticity”. This “arterial elasticity” measurement is
a promising approach to evaluating atherosclerosis [19,20]. Therefore, we applied this method to in vivo detection of regional changes
in human carotid arterial walls. In a study of subjects with type 2
diabetes, carotid arterial elasticity correlated signiﬁcantly with currently established values for atherosclerosis, such as carotid artery
IMT and PWV. Intriguingly, in subjects with IMT <1.1 mm, who areclassiﬁed as not having atherosclerosis as deﬁned by IMT criteria,arterial elasticity correlated with the number of risk factors, i.e.
diabetes, dyslipidemia, hypertension and smoking, suggesting that
arterial elasticity has potential for detecting early stage atherosclerosis. It was also suggested that measuring arterial elasticity would
allow evaluation of qualitative changes in the carotid arterial wall
[21].
Herein, to assess whether the effect of obesity on atherosclerosis can be evaluated using arterial elasticity, we examined theassociations of obesity characteristics with atherosclerosis values
including arterial elasticity, carotid IMT and PWV. We further evaluated the impact of fat distribution on atherosclerosis.
1. Methods
1.1. Study subjects
The study subjects were recruited from among patients withBMI over 30 at Tohoku University Hospital. Patients with type 1
diabetes, renal failure (serum creatinine >2.0 mg/dL), severe heart
failure (NYHA functional class 2–4), atrial ﬁbrillation and peripheralarterial disease were excluded from the study. The study protocol
was approved by the Tohoku University Institutional Review Board.
Informed consent was obtained from each patient.
We used the following criteria for the diagnosis of metabolic disorders. Diabetes was deﬁned as fasting blood glucose ≥7.0 mmol/dl(126 mg/dl) and/or hemoglobin A1c ≥6.5%, based on the deﬁnition proposed by the Japan Diabetes Society, or taking antidiabetic
drugs including insulin. Dyslipidemia was deﬁned as LDL cholesterol ≥3.6 mmol/dl (140 mg/dl) and/or triglyceride ≥1.7 mmol/l(150 mg/dl), based on the deﬁnition proposed by the Japan
Atherosclerosis Society in 2007, or taking lipid-lowering drugs. The
subjects whose systolic blood pressure (BP) ≥140 mmHg and/or
diastolic BP ≥90 mmHg (Japanese Society of Hypertension guidelines 2004) or who were taking antihypertensive drugs were169

deﬁned as having hypertension. The subjects who currently smokedwere classiﬁed as current smokers.
1.2. Measurement of arterial wall elasticity
Real-time measurement of regional elasticity in the far wall ofcommon carotid artery (CCA) was achieved based on a previously
described method [22] with ultrasound diagnostic equipment (prototype system by Panasonic), which was specialized for measuring
regional elasticity. With this system, an ultrasound beam sequentially scanned an artery along its length at 32 positions at intervalsof 200 ␮m with a linear type 7.5-MHz probe.
Multiple points were preset from the luminal surface to theadventitia along each beam at constant intervals of 80 ␮m, andthe displacements at these preset points were estimated by applying the phased tracking method to the received echo. A layer was
deﬁned as being between two points, where the distance between
these two points (i.e. the thickness of the layer) was set at 320 ␮m.
As shown in Fig. 1C, minute changes in thickness of the layer wereobtained by subtraction of the displacements at these two points
and then, the strain of the layer was obtained by dividing the change
in thickness by the original thickness (320 ␮m) which was set atthe end diastole. By changing the depth of the layer at intervals of
80 ␮m and applying the same procedure, the strains at multiple
depths were obtained at intervals of 80 ␮m.
The elasticity of each layer was obtained from the maximal strain
and the pulse pressure measured at the upper arm. The maximal
strain is deﬁned by the absolute value of difference between the
maximum and minimum of the measured change in thickness, as
shown in Fig. 1C, and the maximal strain was determined at eachlocation, independent of time.
Using the above procedure, the elasticity was obtained at intervals of 80 ␮m in the direction of depth and 200 ␮m along its length,
as shown in Fig. 1B. Regional elasticity values of multiple sites ineach layer were displayed as shown in Fig. 1A and a mean regionalelasticity value (kPa) of bilateral CCA was used for analysis.
1.3. Measurement of carotid artery intima–media thickness
IMT of the carotid arteries was measured using ultrasound diagnostic equipment (EUB-450, Hitachi Medico, Tokyo, Japan) with anelectrical linear transducer (center-frequency of 7.5 MHz). By Bmode ultrasound, CCA, carotid bulb, and portions of the internaland external carotid arteries on both sides were scanned with thesubject in the supine position. IMT was measured at a point on the
far wall of the CCA, 1 cm proximal to the bifurcation [23], from thelongitudinal scan plane that showed the intima–media boundaries
most clearly.
1.4. Measurement of PWV
PWV values were measured using an automatic waveform analyzer (BP-203RPE; Colin Co., Komaki, Japan) [24]. Pulse waves wererecorded on the right brachial artery and both posterior tibial arteries. The average PWV was calculated by dividing the arm–ankle
distance by the pulse wave transmission time between these points
on both sides.
1.5. Measurement of abdominal fat area
Abdominal subcutaneous and intra-abdominal fat areas were
measured by CT scans with a SOMATOM Deﬁnition (Siemens AG.,
Munich, Germany) at the level of the fourth lumbar vertebra. The
border of the intra-abdominal cavity was outlined on the CT image
and the total area of visceral fat was measured at an attenuation
range of −200 and −50 Hounsﬁeld units [25].

170

A. Tokita et al. / Atherosclerosis 206 (2009) 168–172

Fig. 1. Evaluation of carotid artery elasticity by phase tracking method. Arterial elasticity is displayed as a 2D cross-sectional color image, which is updated at every heartbeat(A). Multiple sites are preset from the luminal surface to the adventitia (113 depths × 32 beams per 9 mm × 6.4 mm scanned area) and elasticity in each module is measured
by the phase tracking method (B). The arterial wall was divided into multiple layers with thicknesses set at 320 ␮m. The changes in thickness at each depth during the cardiac
cycle are simultaneously obtained, and the maximum change in thickness corresponds to the elasticity in each module (C). The elasticity distribution is shown as a histogram(D).

1.6. Statistical analysis
Variables were compared using Pearson’s regression analysis.
Then, a multiple linear regression analysis was performed to evaluate the independent parameters that were signiﬁcantly related toarterial elasticity. All data are expressed means ± S.D., and a p-valueless than 0.05 was accepted as indicating statistical signiﬁcance.
All statistical analyses were performed using the Statistical Package for the Social Sciences version 13.0 (SPSS Japan Inc., Tokyo,
Japan).
2. Results
The clinical characteristics of 78 subjects are shown in Table 1.
Mean age is 41.0 ± 13.9 years, BMI 37.6 ± 7.2 (kg/m2 ). Thus, the sub-jects were relatively young and categorized as having moderate,
extreme or severe obesity according to Japanese guidelines.
To assess the clinical relevance of carotid artery elasticity
in obese subjects, the arterial elasticity value was compared toatherosclerosis values obtained with currently established methods, carotid IMT and PWV. Arterial elasticity showed signiﬁcant
positive correlations with both carotid IMT (r = 0.422, p < 0.01) andPWV (r = 0.360, p < 0.01) in obese subjects (Fig. 2). Similar positive correlations among these three atherosclerosis values wereobserved in our previous results in subjects with type 2 diabetes[21]. The IMT value in this study was 0.61 ± 0.17 (range: 0.30–1.20)mm and PWV was 1396 ± 260 (range: 992–2117) cm/s, i.e. theseobese subjects did not have advanced atherosclerosis, in contrast
to the results in subjects with type 2 diabetes in our previous study(IMT: 0.94 ± 0.30 mm, PWV: 1703 ± 356 cm/s).
We then explored the association of carotid arterial elasticity
with the clinical and demographic characteristics of these obese

Table 1
Subject characteristics.
NumberAge, years
Gender (male), %Body weight, kg
BMI, kg/m2
Fasting blood glucose, mg/dl
HbA1c, %Serum insulin ␮U/ml
HOMA-R
Systolic BP, mmHg
Diastolic BP, mmHg
Total cholesterol, mg/dl
HDL cholesterol, mg/dl
LDL cholesterol, mg/dl
Triglyceride, mg/dl
Uric acid, mg/dl
Visceral fat area, cm2
Subcutaneous fat area, cm2
Diabetes, %Dyslipidemia, %Hypertension, %Current smoker, %Mean ± S.D.

78
41.0 ± 13.9
29.5
98.8 ± 24.2
37.6 ± 7.2
121.3 ± 47.6
6.5 ± 1.8
17.8 ± 13.2
4.5 ± 3.8
126.9 ± 14.4
79.8 ± 10.7
208.2 ± 43.5
45.8 ± 9.6
132.6 ± 32.9
184.1 ± 177.4
5.9 ± 1.5
150.3 ± 55.7
405.7 ± 160.0
46.8
60.3
48.7
28.0

Table 2
Associations between atherosclerosis values and subject characteristics.
Variables

Age
Male
Body weight
BMI
Fasting blood glucose
HbA1c
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglyceride
Systolic BP
Diastolic BP
Uric acid
Diabetes
Dyslipidemia
Hypertension***

p < 0.05.
p < 0.01.

r
Elasticity

IMT

PWV

0.46**
0.27*
0.03
0.07
0.14
−0.02
0.20
−0.03
0.15
−0.03
0.38**
0.28*
0.15
0.15
0.04
0.37**

0.44**
0.24**−0.075−0.06
0.032−0.036
0.061
0.19
0.034
0.005
0.27*
0.26*
0.10
0.091
−0.11
0.39**

0.67**−0.086
−0.11
0.045
0.14
0.00950.030
0.060−0.049−0.0400.35**
0.047−0.20
0.39**
0.037
0.51**

A. Tokita et al. / Atherosclerosis 206 (2009) 168–172

171

Fig. 2. Correlations of arterial elasticity with carotid IMT (A) and PWV (B) in obese subjects.

Table 5Multivariate adjustment for parameters related to visceral fat area.

Table 3
Associations between each atherosclerosis value and fat distribution.
Variables

Visceral fat area
Subcutaneous fat arear
Elasticity

IMT

PWV

0.42**−0.0660.25*−0.111

0.31*
0.046

p < 0.05.
**
p < 0.01.

subjects. As shown in Table 2, arterial elasticity correlated withage (r = 0.46, p < 0.01), gender (r = 0.27, p < 0.05), BP, both systolic(r = 0.38, p < 0.01) and diastolic (r = 0.28, p < 0.05), and hypertension (r = 0.37, p < 0.01). Carotid IMT and PWV also showed similar
associations with age, systolic BP and hypertension.
To evaluate whether fat distribution affects atherosclerosis
in obese subjects, we performed a single regression analysis ofatherosclerosis values with subcutaneous or visceral fat accumulation, as determined by CT scanning. Interestingly, visceral fat area
correlated signiﬁcantly with arterial elasticity as well as carotid
IMT and PWV (Table 3), whereas subcutaneous fat area showed
no apparent association with these three atherosclerosis values
in the present study. Then, we performed multiple linear regression analysis with parameters related to atherosclerosis values, i.e.
age, hypertension and visceral fat area (Tables 2 and 3), to search
for independent variables affecting atherosclerosis values in obese
subjects. As shown in Table 4, each atherosclerosis value is associated with age, indicating that age is also a strong atherosclerosis
determinant in obese subjects. Intriguingly, the analysis revealed
that visceral fat area is an independent variable showing a positive correlation with carotid arterial elasticity, but not carotid IMTor PWV. We next analyzed the results in a different way, to determine which of the atherosclerosis values is most strongly associatedwith visceral adiposity. Visceral fat area was signiﬁcantly associated with both arterial elasticity and PWV, though the correlation
with arterial elasticity was stronger (Table 5). These results suggest

Table 4Multivariate adjustment for parameters related to atherosclerosis values.

AgeVisceral fat area
HypertensionaR2 = 0.32.
R2 = 0.25.
c
R2 = 0.47.
*
p < 0.05**
p < 0.01.
bRegression coefﬁcientpElasticity
IMT
PWV

0.34
0.034
0.22

0.0041
0.77
0.047

R2 = 0.23.

*

Variables

Variables

Regression coefﬁcient
Elasticitya

IMTb

PWVc

0.30*
0.28**
0.13

0.34**
0.075
0.019

0.52**−0.06
0.32*

that arterial elasticity is an excellent parameter of atherosclerosis
as compared with currently established atherosclerosis values andmight reﬂect the cardiovascular risk of visceral adiposity.
3. Discussion
We measured two established atherosclerosis values, carotid
IMT and PWV, in addition to “arterial elasticity”, which was measured by a novel method, in this study. Similar to our previous
results in subjects with type 2 diabetes [21], the arterial elasticity value was signiﬁcantly associated with those of carotid IMT and
PWV. These results raise the possibility of evaluating atherosclerosis in obese subjects with this novel method of measuring elasticity.
The important ﬁnding of the present study is that arterial elasticity
is a better measurement than either carotid IMT or PWV for evaluating the effect of visceral fat accumulation on atherosclerosis inobese subjects; the multiple linear regression analysis revealed that
only carotid arterial elasticity, not carotid IMT or PWV, showed apositive correlation with visceral fat area.
In addition, our present results clearly shows that visceral adiposity rather than subcutaneous adiposity is an important factor
affecting atherosclerosis in Japanese obese subjects with BMI over
30, since all three parameters for evaluating atherosclerosis, arterial elasticity, carotid IMT and PWV, were signiﬁcantly associatedwith visceral fat area but not with subcutaneous fat area. Abdominal fat accumulation, especially visceral adiposity, is well known
to play a crucial role in the development of metabolic syndrome[26], leading to atherosclerosis and ultimately cardiovascular disease [6]. Indeed, visceral adiposity determined by CT scanning was
related to the incidence of coronary artery disease [8]. Furthermore, recent reports have shown several surrogate markers foratherosclerosis, such as carotid IMT [9–13] and arterial stiffness[15], to be associated with intra-abdominal fat accumulation in
subjects without advanced atherosclerosis. Since obesity is increasing explosively world-wide, a practical and non-invasive method isurgently needed for early detection of atherosclerosis before serious
cardiovascular events occur.
Herein, we have shown that our novel method of measuring arterial elasticity has potential for detecting early stage
atherosclerosis in obese subjects. This ultrasonic method accurately
tracks arterial wall movements based on both the phase and the172

A. Tokita et al. / Atherosclerosis 206 (2009) 168–172

magnitude of demodulated signals, allowing instantaneous determination of the position of an object. With this method, it is possible
to accurately detect small-amplitude velocity signals, less than a
few micrometers, which are superimposed on arterial motion due
to the heartbeat. Thus, the values obtained with this method reﬂect
an important characteristic of vessel walls, i.e. arterial elasticity. We
previously reported arterial elasticity to be a promising method of
evaluating early stage atherosclerosis in subjects with type 2 diabetes [21]. Taken together with the present results in obese subjects,
these ﬁnding indicate that measurement of arterial elasticity might
be broadly applicable to evaluation of subjects with atherosclerosisprone metabolic disorders.
This novel method also has potential for evaluating the elasticity distribution in vessel walls with high spatial resolution; theelasticity distribution is demonstrated as a histogram as shownin Fig. 1D. Properties of the histogram, such as deviation and theshape of the distribution, which were not used in this study, would
provide additional information regarding qualitative changes inatherosclerosis. This possibility should be pursued in future investigations.
Several studies have examined which obesity-related values,
including body weight, BMI, waist–hip ratio and abdominal fat
accumulation, are closely associated with atherosclerosis values
such as carotid IMT [27,28] and PWV [29]. However, comparisonsamong these atherosclerosis values were not conducted, i.e., whichof the atherosclerosis values, IMT, PWV or elasticity, is most strongly
associated with obesity-related values remains to be determined.
This is the ﬁrst report demonstrating arterial elasticity to have astronger association with visceral fat area in obese subjects than
the two most widely used atherosclerosis values, IMT and PWV.
The present study has several limitations. The study design
was cross-sectional. Determination of whether arterial elasticity predicts cardiovascular events in the future thus awaits aprospective study. Another issue warranting further investigation
is whether reducing visceral adiposity would improve arterial elasticity. Another important issue is that only approximately 30% of
our study subjects were male. The difference in fat distribution
by gender is well known, i.e. visceral adiposity is more frequently
observed in males [30] and subcutaneous adiposity in females [25].
However, despite the female dominance in our subject group, theeffect of visceral adiposity on arterial elasticity was conﬁrmed bymultiple regression analysis, implying a crucial role of visceral fat
in atherosclerosis.
In conclusion, the present results indicate that arterial elasticity is a novel, sensitive parameter for evaluating atherosclerosis inobese subjects, potentially more useful than currently establishedatherosclerosis values. Measuring arterial elasticity hold promiseof detecting minute vascular changes in early stage atherosclerosis,
and may have broad clinical applications for evaluating atherosclerosis in subjects with metabolic disorders.
Acknowledgments
This work was supported by a Grant-in-Aid for ScientiﬁcResearch (19591031) to Y. Ishigaki and the Global-COE Programs
to Y. Oka from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was also supported by
a Grant-in-Aid for Research on Human Genome, Tissue Engineering (H17-genome-003) to Y. Oka. We thank Dr. T. Ohkubo for helpful
suggestions on the statistical analysis. We also thank N. Tamura fortechnical support.
References[1] Friedman JM. A war on obesity, not the obese. Science 2003;299:856–8.

[2] Yusuf S, Hawken S, Ounpuu S, et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case–control study. Lancet
2005;366:1640–9.
[3] Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet
2005;365:1415–28.
[4] Klein S, Burke LE, Bray GA, et al. Clinical implications of obesity with speciﬁc focus on cardiovascular disease: a statement for professionals fromthe American Heart Association Council on Nutrition, Physical Activity, andMetabolism: endorsed by the American College of Cardiology Foundation. Circulation 2004;110:2952–67.
[5] Poirier P, Eckel RH. Obesity and cardiovascular disease. Curr Atheroscler Rep
2002;4:448–53.
[6] Matsuzawa Y. Therapy Insight: adipocytokines in metabolic syndrome andrelated cardiovascular disease. Nat Clin Pract Cardiovasc Med 2006;3:35–42.
[7] Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S. Contribution of intra-abdominal
fat accumulation to the impairment of glucose and lipid metabolism in humanobesity. Metabolism 1987;36:54–9.
[8] Nakamura T, Tokunaga K, Shimomura I, et al. Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men.
Atherosclerosis 1994;107:239–46.
[9] Yamamoto M, Egusa G, Hara H, Yamakido M. Association of intraabdominal
fat and carotid atherosclerosis in non-obese middle-aged men with normal
glucose tolerance. Int J Obes Relat Metab Disord 1997;21:948–51.
[10] Kim SK, Kim HJ, Hur KY, et al. Visceral fat thickness measured by ultrasonography can estimate not only visceral obesity but also risks of cardiovascular andmetabolic diseases. Am J Clin Nutr 2004;79:593–9.
[11] Liu KH, Chan YL, Chan JC, Chan WB. Association of carotid intima–media
thickness with mesenteric, preperitoneal and subcutaneous fat thickness.
Atherosclerosis 2005;179:299–304.
[12] Lear SA, Humphries KH, Kohli S, Frohlich JJ, Birmingham CL, Mancini GB. Visceral adipose tissue, a potential risk factor for carotid atherosclerosis: resultsof the Multicultural Community Health Assessment Trial (M-CHAT). Stroke
2007;38:2422–9.
[13] Kawamoto R, Ohtsuka N, Ninomiya D, Nakamura S. Association of obesity andvisceral fat distribution with intima–media thickness of carotid arteries in
middle-aged and older persons. Intern Med 2008;47:143–9.
[14] Snell-Bergeon JK, Hokanson JE, Kinney GL, et al. Measurement of abdominal fat
by CT compared to waist circumference and BMI in explaining the presence ofcoronary calcium. Int J Obes Relat Metab Disord 2004;28:1594–9.
[15] Sutton-Tyrrell K, Newman A, Simonsick EM, et al. Aortic stiffness is associatedwith visceral adiposity in older adults enrolled in the study of health, aging,and body composition. Hypertension 2001;38:429–33.
[16] Orr JS, Gentile CL, Davy BM, Davy KP. Large artery stiffening with weight gainin humans: role of visceral fat accumulation. Hypertension 2008;51:1519–24.
[17] Kanai H, Hasegawa H, Ichiki M, Tezuka F, Koiwa Y. Elasticity imaging ofatheroma with transcutaneous ultrasound: preliminary study. Circulation
2003;107:3018–21.
[18] Hasegawa H, Kanai H, Hoshimiya N, Koiwa Y. Evaluating the regional elastic
modules of a cylindeicl shell with nonuniform wall thickness. J Med Ultrason
2004;31:81–90.
[19] Kanai H, Sato M, Koiwa Y, Chubachi N. Transcutaneous measurement and spectrum analysis of heart wall vibrations. IEEE Trans Ultrason Ferroelectr Freq
Control 1996;43:791–810.
[20] Kanai H, Koiwa Y, Zhang J. Real-time measurement of local myocardium motion
and arterial wall thickening. IEEE Trans Ultrason Ferroelectr Freq Control
1999;46:1229–41.
[21] Okimoto H, Ishigaki Y, Koiwa Y, et al. A novel method for evaluating human
carotid artery elasticity: possible detection of early stage atherosclerosis insubjects with type 2 diabetes. Atherosclerosis 2008;196:391–7.
[22] Hasegawa H, Kanai H, Hoshimiya N, Chubachi N, Koiwa Y. Accuracy evaluationin the measurement of a small change in the thickness of arterial walls andthe measurement of elasticity of the human carotid artery. Jpn J Appl Phys
1998;37:3101–5.
[23] Sidhu PS, Desai SR. A simple and reproducible method for assessing intimal–medial thickness of the common carotid artery. Br J Radiol
1997;70:85–9.
[24] Munakata M, Ito N, Nunokawa T, Yoshinaga K. Utility of automated brachial
ankle pulse wave velocity measurements in hypertensive patients. Am J Hypertens 2003;16:653–7.
[25] Kvist H, Sjostrom L, Tylen U. Adipose tissue volume determinations in womenby computed tomography: technical considerations. Int J Obes 1986;10:53–67.
[26] Bjorntorp P. Metabolic implications of body fat distribution. Diabetes Care
1991;14:1132–43.
[27] Takami R, Takeda N, Hayashi M, et al. Body fatness and fat distribution as predictors of metabolic abnormalities and early carotid atherosclerosis. Diabetes
Care 2001;24:1248–52.
[28] Ingelsson E, Sullivan LM, Fox CS, et al. Burden and prognostic importance of subclinical cardiovascular disease in overweight and obese individuals. Circulation
2007;116:375–84.
[29] Yamada J, Tomiyama H, Matsumoto C, et al. Overweight body mass index classiﬁcation modiﬁes arterial stiffening associated with weight gain in healthy
middle-aged Japanese men. Hypertens Res 2008;31:1087–92.
[30] Kvist H, Chowdhury B, Sjostrom L, Tylen U, Cederblad A. Adipose tissue volume determination in males by computed tomography and 40K. Int J Obes
1988;12:249–66.