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European Journal of Internal Medicine 16 (2005) 580 – 584

www.elsevier.com/locate/ejim

Original article

Arterial stiffness index as a screening test for cardiovascular risk: A


comparative study between coronary artery calcification determined
by electron beam tomography and arterial stiffness index determined
by a VitalVision device in asymptomatic subjects
Sekip Altunkan a,*, Kamuran Oztas a, Besim Seref b

a
Hypertension Division, Metropol Medical Center, Nisan Sokak, No. 7, 06400, Dikmen, Ankara, Turkey
b
Scientific Education and Health Research Centre, Ankara, Turkey

Received 15 February 2005; received in revised form 10 June 2005; accepted 23 June 2005

Abstract

Background: Arterial stiffness has recently been proposed as a powerful independent predictor of cardiovascular disease. However, the
influence of arterial stiffening on the interaction between the heart and large vessels and atherosclerosis is not well defined. The arterial
stiffness index (ASI) has recently been determined with a new device (VitalVision) that calculates ASI in the upper arm using computerized
oscillometry. Coronary artery calcification (CAC) is a useful surrogate marker of coronary artery disease detected non-invasively by electron
beam tomography (EBT). We investigated the correlation between ASI and CAC in a group of patients.
Methods: CAC and ASI measurements were determined with EBT and a VitalVision device, respectively, on the same day in 97
asymptomatic patients. Patients with calcium scores above 0 were classified as CAC+ and those with calcium scores equal to 0 were
classified as CAC . The ASI index was divided into three groups – mild, moderate, and high – according to the H-value, provided by the
VitalVision device.
Results: In patients below 51 years of age, no correlation between the ASI and CAC was found. In patients over 50 years of age, a moderate
positive and significant correlation was found between the CAC score and ASI measurements (r = 0.40, p = 0.001).
Conclusions: The presence of a correlation between the CAC and ASI in patients over 50 shows that the ASI can be used to investigate
atherosclerotic risk.
D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Keywords: Arterial stiffness; Coronary artery calcification; Arterial stiffness index; Electron beam tomography

1. Introduction important determinant of pulse pressure, left ventricular


load, and coronary perfusion pressure in the elderly and,
Arterial stiffness, an early characteristic of vasculopathy therefore, it is the root cause of cardiovascular complica-
involving several mechanisms, results in impaired arterial tions and events [3].
compliance and has recently been proposed as a powerful The influence of stiffness is apparent on the non-
independent predictor of cardiovascular disease [1]. How- invasively recorded arterial pressure wave. The arterial
ever, the influence of arterial stiffening on the interaction pressure wave has two principal components: the wave
between the heart and large vessels and on atherosclerosis is generated by the heart, which travels away from the heart,
less well understood [2]. Arterial stiffness is the most and the reflected wave, which returns to the heart from
peripheral sites [1]. Three types of arterial stiffness can be
considered: systemic, regional or segmental, and local.
* Corresponding author. Fax: +90 312 4831656. Some devices can measure more than one type of arterial
E-mail address: saltunkan@veezy.com (S. Altunkan). stiffness [4].
0953-6205/$ - see front matter D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.ejim.2005.06.011
S. Altunkan et al. / European Journal of Internal Medicine 16 (2005) 580 – 584 581

The arterial stiffness index (ASI), measured by a simple myocardial infarction, bypass surgery, stent placement, or
automatic technique, has recently been used as an index of balloon angioplasty, as well as those who described angina
arterial stiffness and as a cardiovascular risk factor [5]. A pectoris-like chest pain, were excluded. Patients with a
recently developed ASI measuring device is the ‘‘Vital- serum creatinine over 1.5 mg/dl and who were undergoing
Vision’’ (Mars Medical, Taipei, Taiwan), which measures dialysis were also excluded from the study. Being hyper-
and calculates the ASI in the upper arm using computerized tensive was defined as having a systolic blood pressure of
oscillometry. 140 mmHg or higher or a diastolic blood pressure of 90
Coronary artery calcification (CAC) is a part of the mmHg or higher or being on antihypertensive drugs.
atherosclerotic process and predicts coronary artery disease Following an overnight fast, blood samples were taken
(CAD) events in both asymptomatic and symptomatic from patients for direct laboratory analysis. Diabetes
subjects [6]. CAC is a useful surrogate marker of CAD mellitus was defined as having a blood glucose value of
and it can be detected non-invasively by means of electron 126 mg/dl or more or the use of anti-diabetic drug treatment.
beam tomography (EBT) [7,8]. EBT is currently the All subjects signed a written informed consent form, which
ultimate standard for calcium detection in coronary arteries had the approval of the local Institutional Review Board at
[9]. the Metropol Medical Centre.
The aim of our study was to determine the correlation
between ASI and CAC, a marker of sub-clinical atheroscle- 2.2. EBT
rosis in asymptomatic subjects.
The EBT studies were performed using the GE Imatron
C150 XP EBT scanner (San Francisco, CA, USA).
2. Methods Coronary visualization was achieved without contrast using
high resolution with a 100-ms scan time, a 3-mm slice
2.1. Patients thickness, RR interval ECG triggering, and breath-holding.
Forty contiguous axial slices of the heart were obtained with
THE risk of CAD in 97 consecutive, asymptomatic, self- ECG-gated triggering at 80% of the RR interval. The lesion
referred subjects who underwent EBT at the Metropol score, calculated by multiplying the lesion area by a density
Medical Centre, Ankara, was examined. The patients filled factor derived from the attenuation, was equal to or
out a medical history questionnaire. Those who had had exceeded 130 Hounsfield units. A total calcium score was

Fig. 1. The relationship of arterial pressure – volume and pulse wave (left). In evaluating arterial stiffness, what differs most between a normal (soft, flexible)
artery and a sclerotic artery is the property of the arterial intima and media. The property of the arterial intima and media corresponds to the range of arterial
volume defined between the two points indicated on the pressure – volume curve. ASI (H-value), used to evaluate arterial stiffness, is calculated as the range of
pressure corresponding to the range of arterial volume defined by the two points on the pressure – volume curve multiplied by a factor of 10. The pulse wave
patterns of normal and stiff arteries are shown on the right (adapted from Mars Medical Ltd.).
582 S. Altunkan et al. / European Journal of Internal Medicine 16 (2005) 580 – 584

determined by summing the lesion scores from each of four Table 2


anatomic sites (left main, left anterior descending, circum- Characteristics of patients
flex, and right coronary arteries), as described by Agatston Parameters Mean T S.D.
et al. [7]. Subjects with calcium scores above 0 were Age (years) 56.7 T 11.1
classified as CAC+; those without detectable coronary BMI (kg/m2) 28.7 T 4.5
Men/Women 57/40
calcium were classified as CAC .
Systolic BP (mmHg) 133 T 23
Diastolic BP (mmHg) 84 T 12
2.3. Arterial stiffness index (ASI) and the VitalVision device Fasting serum glucose (mg/dl) 99 T 30
Total cholesterol (mg/dl) 212 T 42.1
ASI is a non-invasive test that indicates the stiffness of Triglycerides (mg/dl) 155 T 82.8
LDL cholesterol (mg/dl) 133.9 T 41.8
the arteries, which in turn describes a key aspect of
HDL cholesterol (mg/dl) 46.9 T 5.2
cardiovascular health. ASI applies the principle that volume Uric acid (mg/dl) 5.5 T 1.4
change in the inner membrane/tunica media of a flexible ASI (bar) 3.8 T 1.7
artery is large under pressure and that volume change in the CAC+ (%) 62
inner membrane/tunica media of a stiff artery under pressure Presence of hypertension (%) 29
Presence of diabetes mellitus (%) 9
is too small to evaluate the arterial elastic modulus from
Presence of smoking habit (%) 27
changes in the pulse wave pattern record. The calculation of
S.D. = standard deviation; BP= blood pressure; ASI = arterial stiffness index;
ASI begins with the conversion of the flat part of the
CAC = coronary artery calcification.
trapezoidal shape of the pulse wave pattern (this flat part
indicates the inner membrane/tunica media region) into
pressure variation. The flat area is determined as the region correlation test. Reliability was tested using the Kappa (j)
between the highest value of the pulse wave pattern and the test. Validity was tested using sensitivity, specificity, and
point where pulse wave amplitude is at 80%. ASI is then positive and negative predictive values. Receiver –operator
calculated as the length of the top of thin flat area where characteristics (ROC) curves were generated to determine
pulse wave variation is within 5% (Fig. 1) [10]. The ASI the predictive power of VitalVision scores. A two-tailed
value varies significantly with changes in the characteristics value of p < 0.05 was considered significant.
of the inner membrane and tunica media, which vary with
arterial stiffness, aging, and increases in pulse pressure.
VitalVision provides an index value, the H-value (arterial 3. Results
hardness value/arterial elasticity index), which quantifies the
degree of arterial stiffness based on variations in the pulse A total of 97 patients (40 women and 57 men) were
wave amplitude obtained while measuring blood pressure. enrolled in the study. Their mean age was 56.7 T 11.1 years.
Classification of the H value and ASI are shown in Table 1. Sixty-two percent of the patients had coronary artery
EBT and ASI measurements of the patients in our study calcification defined as CAC+ (Table 2).
were done on the same day. To obtain the most accurate A high ASI was found in 47 patients (49.0%) and a
blood pressure measurements with the VitalVision device, normal ASI was found in 50 patients (51.0%), as determined
the patients were seated in a chair with back support and by the VitalVision device. Of the patients with a normal
rested their arms on a table so that the cuff was at the same ASI, 28 had a CAC score of 0 (56%), 11 had low CAC
level as the patient’s heart. Right after taking a blood scores (22%), and another 11 had high CAC scores (22%).
pressure measurement, the VitalVision device is capable of Among the patients with a mild ASI, 9 had a CAC score of
giving the H-value, which describes a patient’s arterial 0 (24.3%), 14 had low scores (37.8%), and another 14 had
elasticity. An H-value of 4 bar or greater was considered a high scores (37.8%). Among the patients with a high ASI
cardiovascular risk value. (10 patients), the CAC scores of 8 patients were low (80%)
and those of 2 patients were high (20%), which shows that
2.4. Statistical analysis 100% of patients with a high ASI had CAC+ (Table 3). A
moderate positive and statistically significant correlation
The relationship between the EBT scores and the
VitalVision scores were analyzed using the Spearman’s Table 3
Risk categories according to coronary calcium scores
Table 1 ASI CAC categories (according to the Aganston score)
H-value indication, ASI range, and CAD risk factor 0 1 – 100 101 and above
H-value indication ASI range CAD risk factor (normal) (mild) (moderate and severe)
1 – 3 bar 0 – 80 Normal Normal 28 (56%) 11 (28%) 11 (22%)
4 – 6 bar 81 – 209 Mild to medium stiffness Moderate 9 (24%) 14 (38%) 14 (38%)
7 – 8 bar >210 Stiffness Severe 0 (0%) 8 (80%) 2 (20%)
ASI = arterial stiffness index; CAD = coronary artery disease. ASI = arterial stiffness index; CAC = coronary artery calcification.
S. Altunkan et al. / European Journal of Internal Medicine 16 (2005) 580 – 584 583

Table 4 In our study, in patients below 51 years of age, there


The validity and reliability of ASI measurement with the VitalVision device was no relationship between the ASI and CAC. On the
according to total coronary calcium score measurements with EBT
other hand, in patients over the age of 50, a strong
All patients Age  50 Age 51
relationship was present. This result is in accordance
(N = 97) (n = 33) (n = 64)
with the studies done by Yufu et al. and Weber et al.,
Sensitivity 63.9% 54.5% 66.0%
which used another method for measuring arterial
Specificity 77.8% 77.3% 78.6%
P predictivity 83.0% 54.5% 91.7% stiffness [11,12].
N predictivity 56.0% 77.3% 39.3% A strong correlation between CAC and pulse wave
Reliability (j) 0.39 T 0.08* 0.32 T 0.17** 0.33 T 0.10*** velocity (PWV) was found [13]. According to previous
Spearman’s correlation 0.40 T 0.08* 0.32 T 0.17** 0.37 T 0.17*** studies, a relationship between the PWV and coronary
N = negative; P= positive. plaque burden was [14]. Also, there are other studies that
* p = 0.001. show a correlation between the ASI and PWV [5]. The
** P = 0.07.
results of our study are in accordance with the studies done
*** p = 0.003.
with PWV.
In hypertensive patients with left ventricular hypertrophy,
was found between the CAC score and the ASI measure- the ASI was found to be high in one study [15]. This could
ments (Spearman’s correlation, r = 0.40, p = 0.001). indicate that the ASI may be an indirect method for
In all age groups, the sensitivity, specificity, positive measuring cardiovascular risk.
predictive value, and negative predictive values of the ASI There are many surrogate measures of large artery
measurements according to the CAC scores were 63.9%, stiffness, such as central pulse wave velocity (PWV), stroke
77.8%, 83.0%, and 56.0%, respectively (Table 4). The volume/pulse pressure, elastic modulus, and brachial artery
reliability ratio of measurements done with the VitalVision pulse pressure, which have been shown to be predictive of
device was determined to be 0.39 T 0.08 ( p = 0.001). all causes and cardiovascular mortality [4,16 – 18]. Devices
Among the patients below 51 years of age, the that measure arterial stiffness in the upper arm of patients
sensitivity, specificity, positive predictive value, and nega- can be very practical in determining cardiovascular risk,
tive predictive values of the ASI measurements, according according to previous studies [19,20]. The results of our
to the CAC scores, were 54.5%, 77.3%, 54.5%, and 77.3%, study support this practical method of risk assessment.
respectively (Table 4). In this age group, the reliability of the Determining the ASI index can be useful for early screening
test was calculated to be 32%, but this ratio was not of cardiovascular disease, such as hardening of the arteries.
statistically significant ( p = 0.07). Our study shows that there is a relationship between
In patients older than 50 years of age, the sensitivity, CAC and the ASI in patients over 50 years of age. As is
specificity, positive predictive value, and negative predictive known, CAC is an important test for detecting subclinical
values of ASI measurements, according to the CAC scores, atherosclerosis. However, as its application is expensive and
were 66.0%, 78.6%, 91.7%, and 39.3%, respectively (Table as the EBT equipment used in measurement is not
4). Moderate reliability (j = 0.33) and a positive correlation widespread, this method frequently cannot be applied. The
(Spearman’s, r = 0.37) were found ( p = 0.003). In patients equipment that measures ASI, on the other hand, is
over 50, the VitalVision device yields a high sensitivity and inexpensive and quite commonly used, and it can be applied
a positive predictive value. at many different locations. Moreover, patients can take this
The area under the ROC curve in patients below 51 years measurement on themselves. The major problem regarding
of age, in patients older than 50, and in all of the patients
was determined to be 0.65, 0.72, and 0.71, respectively
(Fig. 2).

4. Discussion

Arterial stiffness index (ASI), as measured by the


VitalVision device in our study, has a statistically significant
association with the presence of coronary calcium deter-
mined by EBT. The presence of CAC is considered to be an
important marker of atherosclerosis [6 –8]. A close rela-
tionship between arterial stiffness and atherosclerotic
changes plus calcifications at the arterial walls has been
Fig. 2. ROC curves for ASI and the presence of coronary artery
established [11,12]. The presence of a positive correlation calcification. The area under the ROC curve for patients over 50 years of
between arterial calcification and the ASI provides impor- age was 0.72, for those under 50 it was 0.65, and in the overall group it was
tant evidence of this relationship found in our patients. 0.71.
584 S. Altunkan et al. / European Journal of Internal Medicine 16 (2005) 580 – 584

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