World Journal of Cardiovascular Diseases, 2013, 3, 433-441 WJCD Published Online October 2013 (
The implication of calcium score and pentraxin-3 in
non-invasive identification of significant coron ary artery
stenosis in chronic stable angina pectoris
Habib Haybar1, Mohammad Davoodi2, Abtin Shahlaee3, Amir Eslami Shahr Babaki4*,
Zahra Fazelinezhad2, Maryam Azarian5, Molook Salemzadeh6
1Cardiovascular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2Radiology Group, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
4Sports Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
5Biology Group, North Tehran Branch, Islamic Azad University, Tehran, Iran
6Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Email: *
Received 22 July 2013; revised 25 August 2013; accepted 9 September 2013
Copyright © 2013 Habib Haybar et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective: Coronary Artery Disease (CAD) would
continue to concern medical society in the foreseeable
future. Determining the extent of coronary luminal
stenosis is a key factor in management of CAD.
Methods presently used are costly and pose certain
dangers, ranging from nephrotoxicity to death. Long
Pentraxin or Pentraxin-3 (PTX3) has been used to
predict survival or atherosclerotic process, but not to
identify coronary stenosis. Calcium Score has been
used to this end with some success. Methods: Indi-
viduals with chronic stable angina, without evidence
of Myocardial Infarction (MI), who were categorized
as intermediate-risk after completing a treadmill ex-
ercise test, according to Duke Protocol, underwent
cardiac catheterization. In addition, blood samples
were drawn for coronary sinus PTX3, and also PTX3,
uric acid, high-sensitivity C-reactive protein (hs-
CRP), cholesterol, glucose and High-Density Lipo-
protein (HDL) in peripheral circulation. Calcium
Scores were calculated using Agatston Score and non-
contrast multi-slice CT scan. Participants were di-
vided according to the number of stenotic coronary
arteries (patent, one-, two- and three-vessel disease).
Results: We found that PTX3 levels in coronary sinus
and femoral vein correlated with each other, after
log-transforming the values. Also we found that
PTX3 levels and Calcium Scores differed among in-
dividuals with triple-vessel involvement and indi-
viduals without significant stenosis in any of coronary
arteries. No significant differences were observed,
regarding hs-CRP levels. Conclusion: PTX3 levels in
periphery correlate with those in coronary arteries,
and this variable can be measured with a less invasive
procedure. In addition to Calcium Score, PTX3 levels
are different in our four groups. The combined con-
tribution of PTX3 and calcium score may help us
identify individuals with significant coronary artery
stenosis without needing to perform cardiac cathe-
terization in a select group of patient s.
Keywords: Coronary Artery Disease; Calcium Score;
Pentraxin-3; Long Pentraxin; hs-CRP; Non-Invasive
Coronary Artery Disease (CAD) is a leading cause of
mortality worldwide [1]. Atherosclerosis of coronary ar-
teries is by far the main etiology of Ischemic Heart Dis-
ease (IHD) and plaque disruption superimposed by
thrombosis is the major cause of Acute Coronary Syn-
dromes (ACS) including Unstable Angina (UA) and
Myocardial Infarction (MI) and sudden death [2,3].
Nearly half of IHD cases are initially manifested by the
process of atherosclerosis in the absence of thrombosis,
which is generally a benign condition and usually pre-
sents itself as chronic stable angina. Chronic stable an-
gina has a financial burden of reaching tens of billions of
US dollars [4].
Duke treadmill score is a scoring system employed in
conjunction with a standard exercise treadmill test to
*Corresponding author.
H. Haybar et al. / World Journal of Cardiovascular Diseases 3 (2013) 433-441
determine the prognosis of chronic stable angina when
the diagnosis is uncertain [4]. In addition to helping
quantify ischemia severity [5], Duke Score enables us to
postpone cardiac catheterization in patients classified as
low-risk. Nevertheless in intermediate-risk patients, at-
tempts to quantify ischemia severity may prove incon-
clusive [6]. Since patients in the intermediate-risk group
are usually referred for cardiac catheterization, which is
costly, needs expertise and is potentially hazardous, a
search is going on to find newer methods and prediction
models, with respect to coronary artery involvement
[6-10]. Furthermore, considering that traditional models
for atherosclerosis risk-stratification mainly determine
the long-term risk of cardiac events, there is a trend to-
wards biomarkers and their use for assessing short-term
risk of cardiovascular events [11].
The significance of C-reactive protein (CRP) and
high-sensitivity CRP (hs-CRP) and their implications in
CAD remains controversial, some studies implying their
levels as predictors of cardiac risk, and some indicating
the contrary [8,12-14].
Pentraxin-3 (PTX-3), initially proposed as an early in-
dicator of innate immunity and inflammatory response, is
also expressed abundantly in cardiac tissue during in-
flammatory processes, in the atherosclerotic lesions, in
circulation in patients affected by arterial inflammation,
especially those suffering from unstable angina. In-
creased expression has also been observed in vitro from
endothelial cells in response to inflammatory agents
[15-17]. PTX-3 is thought to be released specifically in
vascular insults, so it seems reasonable to assume that
measuring its level would provide us with a more reliable
assessment of the course and progression of the athero-
sclerotic processes and corresponding lesions than more
conventional and non-specific inflammatory markers like
CRP. Furthermore, newly published work of Turkish car-
diologists suggests that PTX-3 is more tightly associated
with the complexity and severity of CAD than hs-CRP
[18]. In a study on prognostic significance of long Pen-
traxin in MI, this biomarker was shown to enable predic-
tion of 3-month mortality probability after accounting for
other factors [19].
Yet the association of PTX-3 with cardiovascular dis-
eases as an entity, its associated risk factors, its incidence
or its other associated conditions like the subclinical
forms of cardiovascular disease has not been fully inves-
tigated [20]. Furthermore, different studies suggest that
PTX-3 acts rather locally, therefore, its levels in coro-
nary vessels are related to cardiovascular disorders, in
general. But obtaining blood samples from coronary
vessels is nothing short of performing cardiac catheteri-
zation. As a result, we sought to determine the relation-
ship between PTX-3 levels in coronary sinus and periph-
eral venous blood.
Calcification of atherosclerotic lesions starts early as
plaque formation in human body, albeit in small quanti-
ties, but more advanced lesions are more commonly cal-
cified [10]. Various methods for evaluating and quanti-
fying this aspect of atherosclerotic process have been
used. Spiral CT scanning has a reasonable (91% sensi-
tiveity and 52% specificity compared with angiography,
when looking for calcification) statistical and financial
balanced utility [10]. However, it is still suggested to be
used in conjunction to other more “traditionally” ac-
cepted criteria [20].
To sum up, chronic stable angina affects a relatively
large and growing population with a tremendous associ-
ated cost which is going to increase in developing coun-
tries. Risk assessment is somewhat problematic in a ma-
jor group of these patients, the intermediate-risk group.
We therefore evaluated the role of inflammation markers,
specifically of pentraxin-3, hs-CRP and calcium score in
patients with intermediate risk unstable angina who un-
derwent coronary angiography to determine if there is a
direct relationship between severity of CAD by an-
giographic criteria and these parameters in this specific
2.1. Overview
The study is an observational study on patients with
symptoms suggestive of chronic stable angina. Our main
goal was to determine a reliable guide to help decide
which intermediate-risk patients, classified in this risk
stratum by Duke score, should undergo more invasive
and costly procedures, most importantly cardiac cathe-
terization. Participants underwent sampling from femoral
vein, an interview for collecting demographic data and
other relevant medical history, and cardiac catheterize-
tion during the initial visit. The hypothesis tested was
that a combination of laboratory data including serum
level of inflammatory markers and certain imaging mo-
dalities, which in our study is Multi-slice Computed
Tomography (CT) scanning of heart to determine coro-
nary Calcium Score, is superior to more traditional
measures of risk determination like Duke scoring, espe-
cially in those categorized as intermediate-risk cases.
2.2. Participants
The study population consisted of fifty one females and
forty nine males selected from patients who were seeking
care from the Imam Khomeini Cardiology Clinic, in
Ahvaz, Iran. The patients presented with symptoms sug-
gesting chronic stable angina. All participants were clas-
sified by Duke Score as intermediate-risk upon complet-
ing a treadmill exercise test. None of the patients had an
Electrocardiogram (ECG) diagnostic for MI, a history of
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H. Haybar et al. / World Journal of Cardiovascular Diseases 3 (2013) 433-441 435
MI or laboratory findings of MI, that is elevated levels of
serum Creatinine Phosphokinase, muscle type B (CPKMB)
and Troponin. The study design was passed on to and
approved by both cardiology department of Jundishapur
University of Medical Sciences, Ahvaz, Iran, and Medi-
cal Ethics Committee of the university. Participants were
informed of the study and all gave informed consent to
be recruited to the study.
2.3. Measurements
Demographic data and past medical history of partici-
pants were collected by a trained interviewer using a
pretested questionnaire. Each patient’s blood pressure
was measured twice, each time from the right arm, in the
sitting position, after a fifteen minute rest by the same
examiner using a standard mercury sphygmomanometer.
Mean of the two values was recorded as an individual’s
blood pressure (BP). At the first visit blood samples were
obtained between seven and nine in the morning (7-9
AM) after twelve to fourteen hours of overnight fasting.
Blood samples were taken from the femoral vein before
performing angiography and from the coronary sinus
during the procedure; The JL-JR and MP catheters were
used for blood sampling from coronary sinus. All sam-
ples were centrifuged, kept at 70 degrees Celsius, and
analyzed in the same laboratory at the Imam Khomeini
Hospital, Ahvaz, and the analysis for all samples was
performed on the day of collection. Samples were ana-
lyzed for measuring plasma glucose, total cholesterol,
HDL, Pentraxin-3, hs-CRP and uric acid. Glucose and
total cholesterol measurements were performed with an
enzymatic calorimetric assay using glucose oxidase and
cholesterol esterase and cholesterol, respectively. Ana-
lyses were performed using Pars Azmon kits (Pars Az-
mon Inc., Tehran, Iran), Cusabio kits (Cusabio Biotech,
Wuhan, Hubei Province, China), and a Selectra 2 auto-
analyzer (Vital Scientific, Spankeren, Netherlands). In-
tra-assay standard deviations were below 10% in all of
the tests.
All subjects underwent cardiac imaging with a Sei-
mense Samatom Sensation 64-slice scanner. Imaging was
performed with a 100-milliseconds scanning time and a
single-slice thickness of 3 millimeters. A total of 40
slices were obtained during a single breath-holding pe-
riod. Tomographic imaging was electrographically trig-
gered at 60 percent of the interval between R waves. All
area of calcification within the borders of a coronary
artery with a minimal attenuation of 130 Hounsfield
units was computed. A calcified coronary plaque was
considered present if at least three consecutive pixels
were measured (voxel size, 1.03 cubic millimeters).
2.4. Definitions
A participant was diabetic if fasting plasma glucose
concentration was 126 mg/dl on two separate occasions,
or if the patient was on treatment with insulin or oral
hypoglycemic agents. Smoking was defined as current
smoking or having a history of habitual smoking.
Hypertension was defined as diastolic blood pressure
greater than or equal to 90 mmHg or systolic blood
pressure greater than or equal to 140 mmHg or self-re-
ported use of antihypertensive drugs.
All patients underwent standard coronary angiography
assessment through a femoral approach, with standard
Seldinger techniques performed by the same cardiologist.
Coronary artery stenosis was defined as 70% or more
stenosis of the vessel’s diameter.
The degree of coronary artery calcification was calcu-
lated as described by Agatston et al . [21].
The sum of the scores for all arterial lesions provides
an overall score for each subject.
2.5. Statistical Analyses
Data are presented as mean ± standard deviation (SD)
and frequency (%) for continuous and categorical vari-
ables respectively. Continuous variables were checked
for the normal distribution assumption using the Kol-
mogorov-Smirnov statistics and those that did not satisfy
the criteria were log-transformed to attain normal distri-
bution. The study group was divided into two subgroups
based on angiographic findings. Significant differences
between groups were assessed with unpaired two sided
Student’s t test or the Mann Whitney test for continuous
variables. Heterogeneity of hs-CRP, PTX-3, and calcium
score levels were evaluated using ANOVA or Kruskal-
Wallis ANOVA (for unequal variances) to distinguish
between patients with different degrees of coronary ar-
tery disease.
Categorical variables were tested with Fisher’s exact
or chi square tests. The Pearson coefficient of correlation
was used to assess correlations between variables with
normal distribution. Significance was set at p < 0.05. In
order to assess the diagnostic utility of calcium score and
pentraxin levels and determine the optimal cutoff-points
for predicting CAD, the receiver operator characteristic
(ROC) curve analysis was used with an estimation of the
variable’s sensitivity and specificity. The cutoff-point for
each variable was assessed by the minimum value of
1 sensitivity1 specificity
[23] which repre-
sented the maximum sum of sensitivity and specificity
(MAXss) in each group. In addition to comparing those
with CAD with those who had patent coronary arteries,
we sought to determine the ability of the variables to
distinguish patients with three-vessel disease from the
rest of the participants.
The area under curve (AUC) relates to the overall
ability of using the calcium score and pentraxin level
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H. Haybar et al. / World Journal of Cardiovascular Diseases 3 (2013) 433-441
Copyright © 2013 SciRes.
cutoff-points to discriminate between those with and
without CAD. In this analysis, AUC can be considered
equal to the probability that a randomly drawn individual
from a sample of subjects with CAD has a higher cal-
cium score and/or pentraxin level than a person ran-
domly drawn from the non-CAD sample. AUC can be
interpreted according to the following principles: test
equal to chance (AUC = 0.5) less accurate, (0.5 < AUC
0.7), moderately accurate (0.7 < AUC 0.9), highly ac-
curate (0.9 < AUC 1.0), and perfect performance tests
(AUC = 1.0) (28). Data were analyzed using the SSPS
16.0 for Windows software (SPSS Inc., Chicago, Ill.,
Of all the participants 51% were female and 49% were
male. Sixteen percent were smokers. Mean age was 56 ±
11 years. Thirty three percent were diabetic. Based on
angiographic findings 38% of the participants had patent
coronary arteries, 22% had single vessel involvement,
16% had double vessel involvement, and in 24% all three
coronary arteries were involved. Mean values for HDL
and uric acid levels in serum were 39.61 ± 7.70 milli-
grams/deciliter (mg/dL) and 5.6 ± 2.8 mg/dL, respec-
tively. Based on our definition for hypertension (HTN),
42% of the participants were hypertensive, and 43% had
hyperlipidemia (Ta bl e 1 ). Calcium Score of the partici-
pants had a mean value of 231.57 ± 423.42. Calcium
Scores were divided according to the participants corre-
sponding status, with regard to their coronary arteries
involvement. Minimum values for Calcium Score in in-
dividuals with patent coronaries and single vessel in-
volvement were 0.00 and 1.00, respectively, whereas
these variables for double or triple vessel disease groups
were 15.60 and 86.50, respectively. Mean Calcium scores
for patent coronary artery group, single, double and triple
vessel disease groups were 12.26 ± 23.88, 54.02 ± 62.67,
272.11 ± 228.57, 716.25 ± 609.74, respectively (Table 2).
Determining the correlation between coronary vessel
PTX-3 levels and its level in the periphery concerned the
centerpiece of our study. After log-transformation, coro-
nary PTX-3 levels had a linear association with those in
peripheral circulation, as in the equation loge (coronary
PTX-3) = 0.7973173loge (femoral PTX-3) 0.2155287
(Figure 1). Pearson’s coefficient showed a value of r =
0.75 and p < 0.001, considered satisfactory and indicat-
ing a positive correlation between femoral and coronary
PTX levels.
Participants were divided into two groups of indi-
viduals with patent coronary arteries (Patent), based on
angiographic findings, and those with at least one of their
coronary arteries involved (CAD), as previously defined.
Both groups matched equally for gender distribution,
prevalence of hyperlipidemia, serum level of HDL-C,
Table 1. Demographic, laboratory and imaging findings of study subjects, with respect to the presence of coronary artery disease.
Patent (n = 38) CAD (n = 62) Total (n = 100) p value
Age, years 53 ± 11 59 ± 11 56 ± 11 0.012
Male gender, number (percentage %) 16 (42.1%) 33 (53.2%) 49 (49%) 0.28
Smoking, n (%) 2 (5.3%) 14 (22.6%) 16 (16%) 0.02
Diabetes Mellitus, n (%) 7 (18.4%) 26 (41.9%) 33 (33%) 0.015
Hyperlipidemia, n (%) 14 (36.8%) 29 (46.8%) 43 (43%) 0.33
HDL cholesterol, milligrams/deciliter, mean ± SD 40.00 ± 7.77 39.37 ± 7.71 39.61 ± 7.70 0.62
Hypertension, n (%) 16 (42.1%) 26(41.9%) 42 (42%) 0.99
Uric acid micromole/Liter , mean ± SD 5.2 ± 2.7 5.8 ± 2.8 5.6 ± 2.8 0.26
Positive CRP (qualitative) 7 (18.4%) 18 (29%) 25 (25%) 0.23
Femoral hs-CRP micrograms/deciliter, mean ± SD 3340.2 ± 2841.66 3291.5 ± 2638.653 3310 ± 2703.43 0.93
Coronary hs-CRP micrograms/deciliter, mean ± SD 3482.3 ± 2939.095 2885.2 ± 2431.052 3112.1 ± 2637.2 0.27
Femoral PTX-3 nanograms/milliliter , median
(75th percentile-25th percentile) 0.196 (0.222 - 0.138) 0.223 (0.306 - 0.196) 0.250 ± 0.2024 0.002
Coronary PTX-3 nanograms/milliliter, median
(75th percentile-25th percentile) 0.201 (0.242 - 0.159) 0.260 (0.358 - 0.196) 0.280 ± 0.2367 0.001
Calcium score, median (75th percentile-25th percentile) 3.35 (13.4 - 0.0) 187 (542.2 - 51) 231.57 ± 423.42 <0.001
Coronary artery disease: CAD; Number(s): n; High-density lipoprotein: HDL; High sensitivity C-reactive protein: Hs-CRP; Pentraxin-3: PTX-3; Standard
deviation: SD.
H. Haybar et al. / World Journal of Cardiovascular Diseases 3 (2013) 433-441 437
Table 2. Calcium score in CAD.
Calcium score
Mean Standard deviation Maximum Minimum
One-vessel 54.02 62.67 192.00 1.00
Two-vessel 272.11 228.57 673.70 15.60
Three-vessel 716.25 609.74 2657.30 86.50
Patent 12.26 23.88 127.30 .00
Coronary artery disease: CAD.
Figure 1. Log-transformed femoral and coronary PTX. PTX;
prevalence of hypertension, serum level of uric acid, a
positive qualitative CRP, and either of femoral or coro-
nary artery hs-CRP levels. But a statistically significant
difference existed between two groups regarding age
distribution (p = 0.012), number of smokers (p = 0.02),
and prevalence of DM (p = 0.015), both femoral (p =
0.013) and coronary (p = 0.001) artery PTX-3 levels and
the Calcium Score (p < 0.001). Mean values and standard
deviations of variables are provided in Ta bl e 1. Logistic
regression was applied to account for the differences
between age and prevalence of DM and smoking on
comparing serum PTX-3 levels of coronary and femoral
samples and calcium scores between the two groups with
a confidence interval (CI) of 95 % (Table 3).
Based on our hypotheses the differences between
PTX-3 levels, hs-CRP levels and Calcium Score were
important and invited further investigation. This time the
CAD group was sub-divided into three groups of sin-
gle-vessel disease, two-vessel disease and three-vessel
disease, and a one-way ANOVA was performed. P values
suggested that values for Calcium Score, and femoral
vein and coronary sinus PTX-3 levels had a statistically
significant difference (Ta bl e 4). Comparison of hs-CRP
revealed no significant differences between the groups.
Post hoc comparisons using the Tukey test revealed
that calcium scores were significantly higher in the three
vessel disease groups in comparison to all other groups
(p < 0.001). Calcium score for the two vessel disease
group also showed significantly higher values compared
to that of the patent group (p < 0.05) but was not signifi-
cantly higher than the one vessel disease group (p =
Femoral and coronary PTX-3 levels in the three vessel
disease group were higher than the patent (p < 0.0001),
one vessel disease (p < 0.01), and two vessel disease (p <
0.05) groups.
The prevalence of disease was also assessed for pre-
defined subgroups of patients with an Agatston Calcium
Score smaller than 10, between 10 and 100, between 100
and 400 and greater than 400 based on a previous study
by Rumberger and colleagues [24]. As shown in Table 5,
with increasing calcium score the prevalence of signifi-
cant CAD increased steeply. In patients with a CS <10
the prevalence of significant CAD was 24.2%, whereas
in those with a CS >400 it was 100%.
The ROC curve analysis revealed that the Calcium
Score was a strong indicator of both CAD and three ves-
sel involvement with an area under curve (AUC) of
0.913 (95% CI, 0.86 - 0.97) and 0.944 (95% CI, 0.90 -
0.98) respectively. The optimal cut-off point of Calcium
Score for CAD and three vessel involvement were 34.65
(sensitivity of 80% and specificity of 92%) and 116.5
(sensitivity of 96% and specificity of 84%) respectively.
To a less extent, femoral PTX-3 level was also an indi-
cator of CAD and three vessel involvement with an area
under curve (AUC) of 0.68 (95% CI, 0.57 - 0.79) and
0.83 (95% CI, 0.73 - 0.92) respectively. The optimal cut-
off points of femoral PTX-3 for CAD and three vessel
involvement were 0.22 (sensitivity of 58% and specific-
ity of 74%) and 0.56 (sensitivity of 79% and specificity
of 70%) respectively. A combination of hs-CRP, calcium
score, and PTX-3 achieved an AUC of 0.893 (95% CI,
0.827 - 0.958) for CAD and 0.960 (95% CI, 0.926 -
0.995) for three-vessel involvement.
All of the participants in this study were worried about
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H. Haybar et al. / World Journal of Cardiovascular Diseases 3 (2013) 433-441
Table 3. Comparison of CAD predictors between individuals with patent and stenotic coronary arteries, with and without adjustment
for age, and presence of DM and smoking.
Patent (mean ± SD) CAD (mean ± SD) OR (unadjusted) OR (adjusted)
Calcium Score 12.26 ± 23.875 368.2 ± 493.0 1.04 (1.02 - 1.06) 1.03 (1.01 - 1.06)
Log-transformed femoral PTX-3 1.7 ± 0.36 1.4 ± 0.5 4.6** (1.5 - 13.7) 3.7* (1.1 - 11.8)
Log-transformed-coronary PTX-3 1.6 ± 0.32 1.3 ± 0.55 6.7** (2.1 - 21.6) 7** (1.9 - 26.2)
Coronary artery disease: CAD; Diabetes mellitus: DM; Odds ratio: OR; Pentraxin-3: PTX-3; Standard deviation: SD; *p < 0.05; **p < 0.01.
Table 4. Significance of differences between Pentraxin-3, Calcium score and high-sensitivity C-reactive protein among patients with
varying numbers of involved coronary arteries.
Patent One vessel disease Two vessel diseaseThree vessel disease ANOVA p
Femoral hs-CRP micrograms/deciliter 3340 ± 2841.66 3842 ± 2824.730 2572 ± 2411.747 3266 ± 2595.461 0.567
Coronary hs-CRP micrograms/deciliter 3482 ± 2939.095 3125 ± 2519.943 2059 ± 1935.683 3217 ± 2605.439 0.346
Calcium Score 12.26 ± 23.88 54.02 ± 62.67 272.1 ± 228.57 716.25 ± 609.74 <0.0001
Femoral PTX-3 nanograms/milliliter 0.197 ± 0.083 0.21 ± 0.070 0.21 ± 0.070 0.398 ± 0.357 <0.0001
Coronary PTX-3 nanograms/milliliter 0.202 ± 0.060 0.24 ± 0.084 0.26 ± 0.166 0.45 ± 0.411 <0.0001
ANOVA indicates 1-way ANOVA for equal variances or Kruskal-Wallis ANOVA for unequal variances. Values are mean± SD. High-sensitivity C-reactive
protein: Hs-CRP; Pentraxin-3: PTX-3.
Table 5. Prevalence of disease based on Calcium Score.
Patent CAD
CountPercent CountPercent
<10 25 75.8% 8 24.2%
<100 12 40.0% 18 60.0%
<400 1 5.6% 17 94.4%
Calcium score
>400 0 0.0% 18 100.0%
Coronary artery disease: CAD.
their health and wanted to know whether they were in a
serious peril. Every clinician tries to console his or her
patients in a scientifically justifiable manner and would
therefore employ the most accurate means, however one
must not forget that clinical practice is a delicate balance
between ethical, medical, financial and more elements.
Hence it is always prudent to develop cost-efficient, ac-
curate and reliable medical methods.
Demographically the participants in this study were
not different from the patient population seeking medical
attention in everyday clinical situations. Risk factors
were not assessed in the present study; however those
detected in our subjects correspond with established risk
factors, indicated by other studies [25,26]. A cornerstone
of what we propose is the point that serum PTX-3 levels
in peripheral vessels, such as femoral vessels can be re-
liably used instead of coronary level values. It enables us
to measure a variable of our desired equation to predict
coronary artery stenosis, without depending on interven-
tional modalities. What is intriguing is the point that al-
though Calcium Scores are different for different catego-
ries of coronary artery involvement in general, this dif-
ference is significant only when comparing a patient with
all three of coronary arteries involved, with the rest, and
also when comparing two-vessel disease group with pat-
ent coronary group. We could assume Calcium Score by
itself can predict the presence of a two or three-vessel
involvement, but falls short of differentiating between
individuals without any significant coronary artery in-
volvement and those with CAD. One of the powers of
the present study is that the gold standard of diagnosis,
that is, coronary angiography was used to determine sig-
nificant stenosis; as shown in other studies [26] due to
artifact caused by extensive calcification, imaging mo-
dalities like CT angiography may overestimate the extent
of stenosis.
Femoral venous PTX-3 levels were also different
among four groups. However, PTX-3 is a more contro-
versial issue and its role is not yet fully understood [26-
31]. Nevertheless PTX-3 levels were significantly higher
in the individuals with three-vessel stenosis, than any
other groups, and it seems to be a reliable indicator of
significant coronary artery stenosis.
Regardless of its utility in predicting mortality of pa-
tients with CAD, as suggested by other studies [8,12-14],
we found that serum levels of hs-CRP do not correlate
with coronary artery stenosis. Our main objective was to
be able to avoid unnecessary angiography in patients;
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H. Haybar et al. / World Journal of Cardiovascular Diseases 3 (2013) 433-441 439
whether we could predict significant coronary artery
stenosis, ahead of performing cardiac catheterization.
According to our findings serum levels of PTX-3 and
Calcium Scores are much higher in individuals with sig-
nificant stenosis of coronary arteries, than those with pa-
tent vessels. Our argument is that if we consider enough
variables, we may be able to predict the presence of sig-
nificant coronary stenosis. Of course this holds true for
patients within the intermediate-risk category based on a
standard exercise test. As another study on a similar
population had suggested [32], both coronary sinus and
femoral arterial PTX-3 levels are independent predictors
of CAD; also, a combined model of traditional CAD risk
factors and femoral arterial PTX-3 levels would make
net reclassification improvement indices 40% and 15%
regarding cutpoint-free and cutpoint-based assumptions,
Rumberger and colleagues [24] used 10, 100 and 400
intervals for Calcium Score as a basis for categorizing
individuals in order to what. We used the same amounts
and observed that indeed very few individuals without
significant stenosis in any of their coronary arteries had
Calcium Scores higher than 100. However similar argu-
ment cannot be made about Calcium Score in patients
with CAD.
Calculating the Area under Curves considering both
three-vessel disease and the rest of the participants, and
presence of a significant stenosis in any of the coronary
arteries versus patent vessels resulted in the conclusion
that Calcium Score has a satisfactory ability in differen-
tiating the two groups, in both of these settings. PTX-3
can also be used in the same manner. The calculated
AUC for the combination of hs-CRP, PTX-3 and calcium
score for different groups of patients, suggests that cal-
cium score is a better predictor of CAD in our sample
than a combination of hs-CRP, PTX-3 and calcium score;
while among patients with three-vessel involvement,
combined model had a slightly higher AUC, compared to
calcium score alone (0.960 versus 0.944). This finding is
compatible with other findings of our study, regarding
individuals with three-vessel disease.
PTX3 levels in peripheral vessels can reliably be used to
predict coronary level values enabling prediction of
coronary artery stenosis without depending on interven-
tional modalities. Furthermore, Calcium Score calculated
using multi-slice CT scanning, without contrast, is
cheaper, safer and more available than angiography or
CT angiography; however, its utility to determine pres-
ence of significant coronary artery stenosis relies on us-
ing additional inputs, such as serum PTX-3 levels. Still,
the number of stenotic coronary arteries might limit the
applicability of such combined models.
A limitation of our study was that we did not have base-
line values of PTX-3 of our patients for comparison.
Another limitation is related to the point that calcifica-
tion of blood vessels is a natural ongoing process in hu-
man body, and can be altered by changes in metabolism,
particularly that of calcium. As other authors [23] have
pointed out, outside an arbitrary range for age, Calcium
Score may fail to produce the expected results.
It is advisable that future studies be designed to deter-
mine the correlation between Calcium Score and per-
centage of stenosis in the lumen of coronary arteries and
whether it could be used to construct a model for pre-
dicting the behavior of atherosclerotic process in coro-
nary arteries.
Although the mechanisms involved with PTX-3 are
not the main foci of this study, determining the actual
role of PTX-3 in MI plays an essential part in structuring
risk-stratification models that incorporate this variable.
That is, if there are variations in base-line level of PTX-3
due to acute MI, the period between PTX-3 measurement
and onset of acute cardiac event can alter the results of
any study significantly.
Our special thanks go to members of Golestan Hospital Clinical
Development Research Unit for helping us in submission and sub-
mission consultancy Gholamreza Eskandari Joi and for data collection.
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