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Cardiopulmonar y Imaging Original Research

van der Bijl et al.


Agatston Score and Coronary CT Angiography

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Cardiopulmonary Imaging
Original Research

Assessment of Agatston Coronary


Artery Calcium Score Using
Contrast-Enhanced CT Coronary
Angiography
Noortje van der Bijl1
Raoul M. S. Joemai1
Jacob Geleijns1
Jeroen J. Bax 2
Joanne D. Schuijf 2
Albert de Roos1
Lucia J. M. Kroft 1
van der Bijl N, Joemai RMS, Geleijns J, et al.

Keywords: Agatston score, coronary artery calcium, CT


angiography, unenhanced CT
DOI:10.2214/AJR.09.3734
Received October 2, 2009; accepted after revision
January 30, 2010.
1
Department of Radiology, Leiden University Medical
Center, C2-S, Albinusdreef 2, 2333 ZA Leiden, The
Netherlands. Address correspondence to L. J. M. Kroft
(L.J.M.Kroft@lumc.nl).
2
Department of Cardiology, Leiden University Medical
Center, The Netherlands.

AJR 2010; 195:12991305


0361803X/10/19561299
American Roentgen Ray Society

AJR:195, December 2010

OBJECTIVE. The purpose of this article is to evaluate to what extent Agatston scores
may be derived from CT coronary angiography (CTA) examinations, compared with traditional unenhanced CT calcium scores.
MATERIALS AND METHODS. Fifty patients with a CT calcium scoreAgatston
score of zero and 50 patients with a CT calcium scoreAgatston score of 1 or greater whose
CT calcium scores had been calculated and who had undergone CTA using volumetric 320MDCT were included. Agatston scores were obtained at 3.0-mm slices for CT calcium score
and CTA. Method agreement, interobserver agreement, and diagnostic performance of CTA
for detecting coronary calcium were evaluated.
RESULTS. Of 50 patients with a positive CT calcium scoreAgatston score, coronary
artery calcium was detected with CTA in 43 patients by observer 1 (mean CTA score, 102
202; mean CT calcium score, 254 501) and in 46 patients by observer 2 (mean CTA score,
94 147; mean CT calcium score, 272 531). Of the 50 patients with a CT calcium score
Agatston score of zero, 49 (98%, observer 1) and 50 (100%, observer 2) had a zero score
with CTA as well. An intraclass correlation of 0.78 and 0.62 was found between CT calcium
score and CTA (p < 0.01), whereas higher Agatston scores were underestimated with CTA.
For observer 1, the sensitivity, specificity, positive predictive value, negative predictive value,
and diagnostic accuracy for detection of coronary calcium with CTA were 86%, 98%, 98%,
88%, and 92%, respectively, and the corresponding values for observer 2 were 92%, 100%,
100%, 93%, and 96%, respectively. Interobserver agreement was 0.996 for CT calcium score
and 0.93 for CTA.
CONCLUSION. Coronary artery calcium can be detected on CTA images with high accuracy. The Agatston calcium score derived from CTA images shows good correlation with
unenhanced CT calcium score and is highly reproducible. However, higher Agatston scores
are systematically underestimated when derived from CTA images.

oronary artery disease is one of


the leading causes of death.
Quantifying the amount of coronary artery calcium with unenhanced CT calcium score has been shown to
be a reliable noninvasive technique for
screening risk of future cardiac events [1, 2]
and can be quantified by using the Agatston
score [3] or scores such as the volume score
[4] or calcium mass [5]. Large patient studies
have shown that the amount of coronary artery calcium based on the Agatston score is a
strong predictor for risk of myocardial infarction and sudden cardiac death, independently of conventional coronary risk factors
[68].
Absent or low coronary artery calcium has
been shown to be highly accurate in exclud-

ing coronary artery disease in asymptomatic


patients [9, 10]. However, the value of a zero
or low calcium score in symptomatic patients
remains less clear. Several studies have reported the presence of obstructive ( 50%)
noncalcified plaque in up to 8.7% of symptomatic patients with zero or low calcium
scores [1114]. Therefore, in symptomatic
patients, CT calcium score may be followed
by CT angiography (CTA), or CTA may be
performed alone.
CTA with the aid of IV contrast agent injection is widely used for the evaluation of
suspected coronary artery disease. CTA confirms or excludes significant coronary artery
stenosis with high accuracy compared with
invasive coronary angiography [1517]. Furthermore, it has been shown that the presence

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van der Bijl et al.


of coronary artery disease detected with CTA
is of incremental and independent value in
predicting all-cause mortality in symptomatic
patients [1820].
CTA allows visualization of the vessel lumen but also of the vessel wall, including
calcified atherosclerotic plaque [21]. However, the level of contrast enhancement in
the coronary vessels may obscure plaque
and may obviate reliable measurements of
plaque density, especially in noncalcified
plaques. It is conceivable that the amount of
coronary calcium may be estimated by using
the CTA images owing to the relatively high
density of calcified plaques compared with
that of noncalcified plaques. Only a few studies have addressed this issue previously [22
24]. To derive calcium scores from CTA,
these studies increased the threshold values
for coronary calcium from the standard (i.e.,
130 HU) to 350 HU [22, 23] or even 600 HU
[24], to avoid luminal contrast being falsely depicted as coronary artery calcium. The
increase in attenuation threshold resulted in
underestimation [22, 24] or overestimation
of the calcium scores [23], whereas increasing threshold values may lead to decreased
sensitivity for depicting small amounts of
coronary calcium [25].
The purpose of this study was to evaluate to what extent Agatston scores may be
derived from CTA examinations compared
with traditional CT calcium score.
Materials and Methods
Study Population
Fifty patients with an Agatston score of zero
and 50 patients with a positive Agatston score ( 1)
were, per group, consecutively selected from a database of patients who had undergone both unenhanced CT calcium score and contrast-enhanced
CTA investigations for clinical indications (59 men
and 41 women; mean age, 55 11 years; height,
175 20 cm; weight, 82 15 kg). Patients with
coronary stents (n = 5), pacemakers (n = 6), and
prosthetic heart valves (n = 10) had been excluded
beforehand to avoid scoring artifacts. Our institutional review board does not require its approval
for anonymous retrospective technical analysis of
data, as was the case in this study.

CT Protocol
All examinations were performed with a 320MDCT scanner (Aquilion ONE, Toshiba). The
patients had undergone prospectively ECG-gated
unenhanced volumetric CT (to calculate CT calcium score) for scoring the amount of coronary
calcium according to Agatston et al. [3] during the

1300

same session, followed by a prospectively ECGgated contrast-enhanced volumetric CTA for coronary artery evaluation, with (n = 68) or without
(n = 32) functional analysis. To lower the heart
rate, 25100 mg of oral metoprolol was administered to patients with a cardiac frequency exceeding 60 beats per minute, if no contraindications
were present. Mean ( SD) heart rate during scanning was 54 7 beats per minute.
The scan range was planned between the carina
and cardiac apex. Depending on the expected scan
range, a 320 0.5 mm or 280 0.5 mm detector
configuration was used. Immediately before image acquisition, an optimal reconstruction phase
was determined during a breath-hold exercise with
ECG recording. Full cardiac CT calcium score acquisition was performed within a single heart beat
during breath-hold at inspiration. Scan parameters
were 120 kV tube voltage and 200400 mA tube
current (mean, 320 49 mA), depending on patient size and shape (200 mA for small or thin patients, 250 mA for average size patients, and 300
400 mA for large or obese patients). Rotation time
was 0.35 second. Effective radiation dose estimation was based on the doselength product provided by the scanner for each patient and by using the
correction factor 0.017 for chest imaging in adults
[26]. The estimated dose was 1.9 0.3 mSv.
CTA was performed after bolus injection of
5070 mL of iodinated contrast agent (400 mg/mL
iomeprol; Iomeron, Bracco) via antecubital vein
injection with a flow rate of 5.0 mL/s followed by a
20 mL mix of 50% contrast agent and 50% saline,
followed by a 25-mL saline flush using an automatic injector (Stellant CT, MedRad). Bolus tracking was performed by placing a region of interest
in the left ventricle. Image acquisition was automatically started 7 seconds after reaching a predefined threshold difference of 100 HU. Scan parameters dependent on body mass index (BMI)
were as follows: 100 kV and 450550 mA for BMI
1723 (15 patients); 120 kV and 400580 mA for
BMI 2330 (65 patients); and 135 kV and 510 mA
for BMI greater than 30 (20 patients). Mean BMI
was 26 4. Rotation time was 0.35 second. The
scan range for CTA had been planned with the aid
of the CT calcium score scan; care was taken to include the full range of the coronary arteries. Full
cardiac CTA acquisition was performed within a
single heartbeat during breath-hold at inspiration,
with or without functional analysis, including dose
modulation throughout the cardiac cycle. Estimated effective radiation dose was 10.7 5.9 mSv.

Image Reconstruction
Standard reconstruction kernel filters were
used for image reconstruction: FC12 for CT calcium score and FC43 for CTA. For CT calcium

score, nonoverlapping 3.0-mm data sets were reconstructed, which is the standard method used in
clinical practice based on electron-beam CT [3].
Similarly, for CTA, data sets of nonoverlapping
3.0-mm slices were reconstructed for evaluation
of coronary calcium. An additional 0.5-mm CTA
data set, with 0.25-mm increments, that is used
for CTA evaluation in clinical practice was reconstructed. The reconstructions were transferred to
a workstation for analysis.

Analysis
Analysis of coronary artery calcium was performed on a postprocessing workstation (Vitrea
FX, version 1.0, Vital Images) using dedicated
CT calcium score analysis software (VScore, Vital Images). Coronary calcium was defined as an
area of at least three face-connected voxels in
the axial plane in the course of a coronary artery,
with an attenuation threshold value of 130 HU or
greater. Three in-axial-plane face-connected voxels correspond to a minimum lesion area greater
than 1 mm 2, which is used as a reference value in
calcium scoring [6]. Calcium scores of each investigation were calculated and expressed as Agatston scores for standard of reference CT calcium
score and for CTA reconstructions.
Contour drawing was performed by two investigators with 2 years (observer 1) and 4 years (observer 2) of experience in cardiac CT; observer 1
was supervised by a radiologist with 7 years of
experience in cardiac CT. Observers were aware
that patients had been selected on the basis of the
presence (n = 50) or absence (n = 50) of coronary
calcium but were not aware of medical history
of individual patients. Examinations were presented in random order. For CTA, calcifications
that were visually identified in the course of the
coronary arteries were marked by the investigator. The investigator was allowed to compare the
3.0-mm CTA data set with the 0.5-mm CTA data
set. Marking was done on the 3.0-mm data set by
precise contour drawing of visually identified calcium spots after zooming in on the focus, allowing visual identification of individual pixels. Automatic recognition of pixels of 130 HU or greater
was switched off because the design of the coronary calcium analysis program is dedicated for
unenhanced CT. After manual contour drawing,
calcium scores were automatically calculated on
the basis of the 130 HU threshold value. After obtaining the calcium scores in the CTA data sets of
all patients, the calcium scores were obtained in
CT calcium score data sets. With automatic recognition of 130 HU or more, pixels exceeding this
threshold value are colored purple by the postprocessing tool. In each slice (depending on scan
range, 47 or 53 slices), these areas were manually

AJR:195, December 2010

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Agatston Score and Coronary CT Angiography


Fig. 157-year-old man with coronary artery
calcifications.
A and B, CT calcium score images show coronary
artery calcifications (arrows) in left anterior
descending coronary artery. CT calcium score
was calculated with automatic recognition of
130 HU switched off (A) and automatic recognition
switched on (purple color, B). Agatston calcium score
calculated by CT calcium score was 151.
C and D, Coronary artery calcifications (arrows) in
left anterior descending coronary artery are seen on
CT coronary angiography (CTA) images with 3.0 mm
(C) and 0.5 mm (D) reconstruction. Agatston calcium
score was 96 with 3.0 mm CTA reconstruction (C).
Comparison with 0.5 mm CTA reconstruction that is
used in clinical practice for coronary artery lumen
evaluation was allowed (D).

applied to determine a statistically significant difference between the calcium scores obtained with
CT calcium score and CTA. The intraclass correlation coefficient (ICC) was calculated to evaluate method agreement between CT calcium score
and CTA investigations and to assess interobserver
agreement. An ICC less than 0.4 indicated poor reproducibility, an ICC of 0.40.75 indicated fair to
good reproducibility, and an ICC greater than 0.75
indicated excellent reproducibility [30]. The method described by Bland and Altman [31] was used
to study limits of agreement and systematic error
between the two methods and between the two observers, respectively. A p value of less than 0.05
was considered statistically significant.

TABLE 1: CT Calcium Score and Agatston Score Risk Group Distribution


Observer 1
Risk Group,
Agatston
Score
0

No. of
Patients

CT
Calcium
Score

CT
Angiography

0.3 1.6

NS

47
31 20

50

0 0

110

11

3 3

11100

15

42 31

101400

16

188 91

95 53

1158 792

391 401

> 400

Observer 2
CT
Calcium
Score

CT
Angiography

0 0

0.1 0.8

NS

NS

3 4

NS

45 26

< 0.001 198 100


0.01

1243 818

44

NS

29 15

0.02

100 56

< 0.001

339 236

0.01

NoteData are the mean SD Agatston score for 3.0 mm CT calcium score and 3.0 mm CT angiography
reconstructions. NS = not significant.

encircled when present in the course of each coronary artery. Calcium scores were automatically
calculated. A time interval of at least 2 weeks between scoring the CTA and the CT calcium score
was used to prevent recognition bias. Patients
were classified according to Agatston risk groups
as defined by Rumberger et al. [27]. Although this
risk stratification scheme is based on absolute Agatston scores and does not account for patient age,
sex, and race, recent studies have shown that absolute calcium scores may predict cardiovascular
events better than adjusted percentiles [28, 29].

AJR:195, December 2010

Statistical Analysis
Statistical analysis was performed using SPSS
for Windows (version 16.0, SPSS). The diagnostic
performance of CTA in the detection of coronary
artery calcium is presented as sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy; CT calcium score was
used as the standard of reference. The mean and
median calcium scores and SDs were calculated for
CT calcium score and for CTA for the whole group
and for the Agatston risk groups [27]. The Wilcoxons signed rank test for two related samples was

Results
Positive Calcium Score ( 1)
For observer 1, the mean calcium score of
the 50 patients with a positive CT calcium
score was 254 501 (median, 82). At CTA,
coronary calcium was detected in 43 (86%)
of 50 patients, with a mean calcium score of
102 202 (median, 40). Seven patients had
a false-negative calcium score at CTA, with
scores of 1 (n = 4 patients), 2 (n = 1 patient),
4 (n = 1 patient), and 8 (n = 1 patient). Figure 1 shows a comparison of coronary artery
calcium visualization with CT calcium score
and CTA.
For observer 2, the mean calcium score of
the 50 patients with a positive CT calcium
score was 272 531 (median, 82). Coronary
artery calcium was detected in 46 (92%) of
these 50 patients at CTA, with a mean calcium
score of 94 147 (median, 45). Four patients
had a false-negative calcium score, with scores
of 1 (n = 2 patients) and 8 (n = 2 patients).
The distribution of patients within different
Agatston risk groups, as defined by Rumberger et al. [27], is shown in Table 1. No statistically significant difference was found between
CT calcium score and CTA-derived calcium
scores for patients with low calcium scores

1301

Difference Observer 2 (CTCSCTA)

Difference Observer 1 (CTCSCTA)

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van der Bijl et al.

2,000

1,000

1,000

1,000

1,000
1

2,000

10

1,000

100

10,000

Mean Agatston Score Observer 1 ([CTCS + CTA] /2)

10

100

1,000

10,000

Mean Agatston Score Observer 2 ([CTCS + CTA] /2)

Fig. 2Bland-Altman analysis showing limits of agreement and systematic errors for both observers. Results for Agatston calcium scores obtained with CT calcium
score (CTCS) and CT angiography (CTA) are shown for observer 1 (A) and for observer 2 (B). Dashed lines show upper and lower limits of agreement 1.96 SD and 95% CI.
Note that good agreement can be observed for low calcium scores, whereas highest Agatston scores above upper limit of calcium score exceeding 544 (observer 1) and
686 (observer 2) contain systematic error.

TABLE 2: Shift in Risk Group Distribution for CT Calcium Score and CT


AngiographyDerived Agatston Scores
Risk Group,
Agatston
Score
0

Observer 1

Observer 2

No. of
Patients

Shift Up

Shift Down

Total Shift

50

Shift Up Shift Down

Total Shift

110

11

11100

15

101400

16

10

10

> 400

Total

100

23

27

19

20

NoteData the number of patients shifting between Agatston score risk groups. Dashes indicate that no risk
group-shift occurred.

(< 10, both observers). For the patients with


calcium scores exceeding 10 (observer 2) and
100 (observer 1), the calcium score was statistically significantly underestimated by CTA,
with a mean factor of 2.8 (observer 1 range,
2.44.1; observer 2 range, 1.74.5) compared
with the reference method (Table 1).
Despite underestimated calcium scores by
CTA, good ICCs (observer 1, 0.78; observer 2, 0.62) were found between CT calcium
score and CTA-derived calcium scores, showing good-to-excellent agreement between
the two methods for the whole patient group
(both p < 0.01). Bland-Altman plots in Figure
2 show the limits of agreement and systematic error for individual scores and show good
agreement for low calcium scores, whereas
the highest scores (exceeding 466 for observer 1 and 596 for observer 2; for the highest
risk Agatston group, > 400) show systematic

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error resulting from underestimation of CTAderived calcium scores.


Zero Calcium Score (0)
For observer 1, 49 (98%) of the 50 patients
with a zero CT calcium score had a zero score
derived from CTA as well. In one patient, a
calcium score of 5 was calculated. In that patient, contrast enhancement in the left anterior
descending artery was visually interpreted as
coronary calcium. All 50 patients with a zero
CT calcium score scored by observer 2 had a
zero CTA-derived calcium score as well.
Diagnostic Performance for Detecting
Coronary Artery Calcium
For observer 1, the diagnostic performance
and predictive value of CTA for the detection
of coronary artery calcium were as follows:
sensitivity, 86% (95% CI, 7394%); specific-

ity, 98% (95% CI, 88100%); positive predictive value, 98% (95% CI, 86100%); negative
predictive value, 88% (95% CI, 7594%);
and diagnostic accuracy, 92%. For observer 2, the values were as follows: sensitivity,
92% (95% CI, 8097%); specificity, 100%
(95% CI, 91100%); positive predictive value, 100% (95% CI, 90100%); negative predictive value, 93% (95% CI, 8198%); and
diagnostic accuracy, 96%.
The change in classification according
to risk groups for the whole patient population for CTA-derived Agatston scores, compared with the standard of reference CT calcium score, for the two observers is shown
in Table 2. Classification in another risk
group occurred for 27% of patients by using
CTA-derived calcium scores; for observer 1,
downgrading of the Agatston risk group
occurred in 23% of cases, and upgrading of
Agatston risk group occurred in 4% of cases.
For observer 2, classification in another risk
group occurred for 20% of patients by using
CTA-derived calcium scores, whereas downgrading of the Agatston risk group occurred
in 19% of cases, and upgrading of Agatston
risk group occurred in 1% of cases.
Interobserver Variability
Interobserver agreement was excellent for
both the CT calcium scoreAgatston scores
(ICC, 0.997; p < 0.001) as well as the CTAderived Agatston scores (ICC, 0.94; p < 0.001)
for the total group. Also, for the groups with
a positive CT calcium scoreAgatston score,

AJR:195, December 2010

Agatston Score and Coronary CT Angiography

500
Difference CTA Agatston Score
(Observer 1 Observer 2)

Difference CTCS Agatston Score


(Observer 1 Observer 2)

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500

250

250

500

250

500

250

10

100

1,000

Mean CTCS Agatston Score ([Observer 1 + Observer 2]/2)

10

100

1,000

Mean CTA Agatston Score ([Observer 1 + Observer 2]/2)

Fig. 3Bland-Altman analysis showing interobserver agreement, limits of agreement, and systematic errors for Agatston calcium score calculated by both CT calcium
score (CTCS) (A) and CT angiography (CTA) (B). Dashed lines show upper and lower limits of agreement 1.96 SD and 95% CI. Excellent agreement can be observed for
both CTCS as well as CTA-derived calcium scores between two observers (p < 0.001).

excellent interobserver agreement was found


(ICC for CT calcium score, 0.996; ICC for
CTA, 0.93; both p < 0.001). Bland-Altman
plots in Figure 3 show levels of agreement
and systematic error for individual scores and
show excellent observer agreement. In the
highest risk group, a few outliers for CT calcium scoreAgatston scores were found between the two observers. The differences in
Agatston scores between the two observers
for these outliers can be explained by dissimilar inclusion of coronary artery calcium at the
origin of the coronary arteries that was continuous with calcifications in the aortic wall.
Discussion
The main finding of the current study is
that the presence of coronary calcification
can be estimated by using contrast-enhanced
CTA, with excellent diagnostic accuracy,
positive predictive value, and specificity.
Second, the Agatston score derived from
coronary CTA correlates well with unenhanced CT calcium score, which is the standard of reference. Third, both enhanced and
unenhanced CT provide equivalent Agatston
scores when there is a limited amount of coronary calcium, but coronary CTA underestimates the amount of calcium in cases with
higher Agatston scores. Fourth, deriving Agatston scores from coronary CTA can be obtained with a high reproducibility and excellent observer agreement.
The excellent diagnostic accuracy, positive
predictive value, and specificity found in the
current study indicate that coronary calcium

AJR:195, December 2010

can be considered as present with a positive


CTA-derived Agatston score. Although a
good sensitivity and negative predictive value were found, the absence of coronary calcium on CTA may be a false-negative observation of coronary calcium that is actually
present. However, no large amounts of coronary calcium were missed on CTA, because
in missed cases, the actual Agatston score
was low, and within Agatston risk group 10
or less, the median Agatston score was 2.
In two previous studies in which Agatston
scores were derived from CTA investigations,
the detection threshold for coronary calcium
was increased from 130 to 350 HU for CTAderived calcium scores and was compared
with the 130 HU CT calcium score threshold
[22, 23]. One study, which used nonoverlapping 3.0-mm-slice CT calcium score to compare with overlapping 1.25-mm-slice CTA
in 50 patients, reported an overestimation of
CTA Agatston scores by a factor of approximately 3 [23]. It is unclear whether the overestimation found in that study was due to the
inclusion of contrast material exceeding 350
HU or to differences in reconstructed slice
thickness and use of overlapping image reconstruction. With thin-slice overlapping
images, voxel sizes and, thus, partial volume
effect decrease. The chance of a voxel containing sufficient calcification attenuation to
reach the detection threshold increases with
smaller voxels [32], leading to higher scoring
results [25, 33, 34].
Another study used 3.0-mm slices and
2.0-mm increments for both CTA and CT

calcium score [22]. In that study, CTA data


for only 28 of 38 patients were used for analysis, because seven patients with a negative
CT calcium score were not included for CTA
analysis, and CTA analysis could not be performed for another three patients. CTA Agatston scores were underestimated by a factor
of approximately 3 [22], which is the range
of the current study. In the current study, the
traditional threshold value of 130 HU was
used for both CTA-derived calcium scores
and CT calcium score. Good agreement was
found between CT calcium score and CTAderived calcium scores. Although low Agatston scores derived from CTA were not statistically different from the CT calcium score,
a substantial underestimation was found in
the higher risk groups, which led to a downshift of risk group for 2022% of the patients,
whereby 14% of patients shifted from the
high-risk group (calcium score, > 400) to the
intermediate-risk group (calcium score, 100
400). Total shift in risk groups occurred for
2027% of all our patients by visual assessment of coronary artery calcium and by using
the 130 HU threshold value, compared with
57% of analyzed patients in a study that used
automatic assessment and 350 HU as threshold value for detection [23].
Furthermore, in the current study, all
100 CTA studies were included for analysis. Moreover, by using volumetric imaging within a single heartbeat for both the CT
calcium score and CTA acquisitions, the 3D
volume data sets reconstructed to 3.0-mm
slices were technically most comparable. It

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van der Bijl et al.


should be noted that the original Agatston
score and large outcome studies were based
on nonoverlapping 3.0-mm-slice data sets
as well [3, 10]. In symptomatic patients, the
extent of coronary artery calcium has been
shown to provide additional prognostic information over invasive coronary angiography alone [6]. However, even a zero calcium
score may not exclude obstructive coronary
artery disease [1114], and a positive score is
no direct indicator for coronary artery stenosis. Therefore, CT calcium score alone seems
not to be optimal for excluding coronary artery disease in symptomatic patients and is
often followed by CTA.
Now that the CTA technique has developed into a clinical tool that is increasingly
used for coronary artery evaluation in routine clinical practice, CTA rather than CT
calcium score may be used for coronary artery evaluation. CTA allows direct evaluation of the presence and extent of coronary
artery luminal obstruction, whereas CTAbased estimation of the presence and extent
of coronary artery calcium from the same
images may provide additional risk information that may obviate the traditional CT
calcium score. Radiation exposure is of major concern in coronary CTA because of the
associated risk of radiation-induced cancer
[35]. Several methods, including prospective ECG-triggering techniques, have been
developed and have been very effective in
reducing patient dose [36, 37]. If a separate
CT calcium score examination can be avoided by using the CTA examination in deriving
the presence and extent of coronary calcium,
this may aid substantially in further decreasing patient dose.
The present study has some limitations.
Deriving Agatston scores from CTA was
more time consuming than deriving Agatston scores from CT calcium scores (the
standard of reference), with approximately
double the time needed for analysis, because
the reader was not alerted by automatic color
encoding of coronary artery calcium during
evaluation. Also, the scoring method used
may not be available on all workstations and
may be vendor dependent. Application of the
technique in routine clinical practice may require software improvements. Further coronary artery analysis software developments
may facilitate deriving calcium scores from
CTA investigations. Furthermore, although
good method agreement between CT calcium score and CTA-derived calcium scores
was found, it is unclear whether the CTA-de-

1304

rived Agatston scores may be used for actual


risk stratificationeven if a conversion factor is appliedas is done now for the large
patient databases obtained by electron beam
CT [9, 10].
A relatively small group of 100 patients
was used for analysis in this feasibility study,
and patients were selected according to the
presence or absence of coronary calcium (n =
50 patients each). It is not known what the effect of using CTA-derived calcium scores by
means of risk stratification and clinical consequences would be for individual patients, because such studies would require large study
populations other than our selected groups of
50 patients each, because outcome depends
on disease prevalence. It should be noted that
patient risk stratification is not based on the
amount of coronary artery calcium alone but
also depends on patient characteristics and the
presence or absence of other risk factors [2]. It
has been shown that using CTA data, with its
information on luminal narrowing and plaque
composition, has incremental prognostic value over using CT calcium score alone [14, 18,
38]. Therefore, combining the results of luminal narrowing, plaque composition, and calcium score may provide optimal information
for CT-based risk stratification. Radiation
dose was relatively high, because the study
was performed early after installation of the
new scanner type. At that time, the majority of patients (68%) had undergone imaging
that included a functional analysis with a relatively high radiation dose compared with prospective CTA for coronary imaging alone that
is routinely applied today. Also, tube current
settings for CT calcium score have now been
substantially decreased.
In conclusion, coronary artery calcium
can be detected on CTA with high accuracy. The Agatston calcium score derived from
CTA shows good correlation with unenhanced CT calcium score and is highly reproducible. However, higher Agatston scores
are systematically underestimated when derived from CTA.
Acknowledgment
We thank B. J. A. Mertens for statistical
advice.
References
1. Oudkerk M, Stillman AE, Halliburton SS, et al.
Coronary artery calcium screening: current status
and recommendations from the European Society
of Cardiac Radiology and North American Society for Cardiovascular Imaging. Int J Cardiovasc

Imaging 2008; 24:645671


2. Greenland P, Bonow RO, Brundage BH, et al.
ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by
computed tomography in global cardiovascular
risk assessment and in evaluation of patients with
chest pain: a report of the American College of
Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee
to Update the 2000 Expert Consensus Document
on Electron Beam Computed Tomography). Circulation 2007; 115:402426
3. Agatston AS, Janowitz WR, Hildner FJ, Zusmer
NR, Viamonte M Jr, Detrano R. Quantification of
coronary artery calcium using ultrafast computed
tomography. J Am Coll Cardiol 1990; 15:827
832
4. Callister TQ, Cooil B, Raya SP, Lippolis NJ, Russo DJ, Raggi P. Coronary artery disease: improved
reproducibility of calcium scoring with an electron-beam CT volumetric method. Radiology
1998; 208:807814
5. Hoffmann U, Siebert U, Bull-Stewart A, et al.
Evidence for lower variability of coronary artery
calcium mineral mass measurements by multidetector computed tomography in a communitybased cohortconsequences for progression
studies. Eur J Radiol 2006; 57:396402
6. Keelan PC, Bielak LF, Ashai K, et al. Long-term
prognostic value of coronary calcification detected by electron-beam computed tomography in
patients undergoing coronary angiography. Circulation 2001; 104:412417
7. Wong ND, Hsu JC, Detrano RC, Diamond G,
Eisenberg H, Gardin JM. Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular
events. Am J Cardiol 2000; 86:495498
8. Arad Y, Spadaro LA, Goodman K, Newstein D,
Guerci AD. Prediction of coronary events with
electron beam computed tomography. J Am Coll
Cardiol 2000; 36:12531260
9. Shaw LJ, Raggi P, Schisterman E, Berman DS,
Callister TQ. Prognostic value of cardiac risk factors and coronary artery calcium screening for
all-cause mortality. Radiology 2003; 228:826
833
10. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term
prognosis associated with coronary calcification:
observations from a registry of 25,253 patients. J
Am Coll Cardiol 2007; 49:18601870
11. Cheng VY, Lepor NE, Madyoon H, Eshaghian S,
Naraghi AL, Shah PK. Presence and severity of
noncalcified coronary plaque on 64-slice computed tomographic coronary angiography in patients with zero and low coronary artery calcium.
Am J Cardiol 2007; 99:11831186
12. Akram K, ODonnell RE, King S, Superko HR,

AJR:195, December 2010

Downloaded from www.ajronline.org by 112.215.201.231 on 01/16/17 from IP address 112.215.201.231. Copyright ARRS. For personal use only; all rights reserved

Agatston Score and Coronary CT Angiography


Agatston A, Voros S. Influence of symptomatic
status on the prevalence of obstructive coronary
artery disease in patients with zero calcium score.
Atherosclerosis 2009; 203:533537
13. Rubinshtein R, Gaspar T, Halon DA, Goldstein J,
Peled N, Lewis BS. Prevalence and extent of obstructive coronary artery disease in patients with
zero or low calcium score undergoing 64-slice
cardiac multidetector computed tomography for
evaluation of a chest pain syndrome. Am J Cardiol
2007; 99:472475
14. van Werkhoven JM, Schuijf JD, Gaemperli O, et
al. Incremental prognostic value of multi-slice
computed tomography coronary angiography over
coronary artery calcium scoring in patients with
suspected coronary artery disease. Eur Heart J
2009; 30:26222629
15. Mowatt G, Cook JA, Hillis GS, et al. 64-Slice
computed tomography angiography in the diagnosis and assessment of coronary artery disease:
systematic review and meta-analysis. Heart 2008;
94:13861393
16. Miller JM, Rochitte CE, Dewey M, et al. Diagnostic performance of coronary angiography by
64-row CT. N Engl J Med 2008; 359:23242336
17. Meijer AB, YL O, Geleijns J, Kroft LJ. Metaanalysis of 40- and 64-MDCT angiography for
assessing coronary artery stenosis. AJR 2008;
191:16671675
18. Ostrom MP, Gopal A, Ahmadi N, et al. Mortality
incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol 2008; 52:13351343
19. Min JK, Shaw LJ, Devereux RB, et al. Prognostic
value of multidetector coronary computed tomographic angiography for prediction of all-cause
mortality. J Am Coll Cardiol 2007; 50:11611170
20. Hadamitzky M, Freissmuth B, Meyer T, et al. Prognostic value of coronary computed tomographic
angiography for prediction of cardiac events in patients with suspected coronary artery disease.
JACC Cardiovasc Imaging 2009; 2:404411
21. Budoff MJ, Achenbach S, Blumenthal RS, et al. As-

AJR:195, December 2010

sessment of coronary artery disease by cardiac


computed tomography: a scientific statement from
the American Heart Association Committee on
Cardiovascular Imaging and Intervention, Council
on Cardiovascular Radiology and Intervention, and
Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 2006; 114:17611791
22. Muhlenbruch G, Wildberger JE, Koos R, et al.
Coronary calcium scoring using 16-row multislice
computed tomography: nonenhanced versus contrast-enhanced studies in vitro and in vivo. Invest
Radiol 2005; 40:148154
23. Hong C, Becker CR, Schoepf UJ, Ohnesorge B,
Bruening R, Reiser MF. Coronary artery calcium:
absolute quantification in nonenhanced and contrast-enhanced multi-detector row CT studies.
Radiology 2002; 223:474480
24. Glodny B, Helmel B, Trieb T, et al. A method for
calcium quantification by means of CT coronary
angiography using 64-multidetector CT: very
high correlation with Agatston and volume scores.
Eur Radiol 2009; 19:16611668
25. Muhlenbruch G, Klotz E, Wildberger JE, et al.
The accuracy of 1- and 3-mm slices in coronary
calcium scoring using multi-slice CT in vitro and
in vivo. Eur Radiol 2007; 17:321329
26. Menzel HG, Schibilla H, Teunen D, et al. European guidelines on quality criteria for computed
tomography: report no. EUR 16262 EN. Luxembourg: European Commission, 2000.
27. Rumberger JA, Brundage BH, Rader DJ, Kondos
G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines
for use in asymptomatic persons. Mayo Clin Proc
1999; 74:243252
28. Budoff MJ, Nasir K, McClelland RL, et al. Coronary calcium predicts events better with absolute
calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2009; 53:345352
29. Akram K, Voros S. Absolute coronary artery calcium scores are superior to MESA percentile rank
in predicting obstructive coronary artery disease.

Int J Cardiovasc Imaging 2008; 24:743749


30. Rosner B. Multisample inference. Fundamentals
of biostatistics, 5th ed. Belmont: Duxbury Press,
2000:563
31. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1:307310
32. Muhlenbruch G, Thomas C, Wildberger JE, et al.
Effect of varying slice thickness on coronary calcium scoring with multislice computed tomography in vitro and in vivo. Invest Radiol 2005;
40:695699
33. Sabour S, Rutten A, van der Schouw YT, et al.
Inter-scan reproducibility of coronary calcium
measurement using multi detector-row computed
tomography (MDCT). Eur J Epidemiol 2007;
22:235243
34. Groen JM, Greuter MJ, Schmidt B, Suess C,
Vliegenthart R, Oudkerk M. The influence of
heart rate, slice thickness, and calcification density on calcium scores using 64-slice multidetector computed tomography: a systematic phantom
study. Invest Radiol 2007; 42:848855
35. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation
exposure from 64-slice computed tomography
coronary angiography. JAMA 2007; 298:317323
36. Earls JP, Berman EL, Urban BA, et al. Prospectively gated transverse coronary CT angiography
versus retrospectively gated helical technique:
improved image quality and reduced radiation
dose. Radiology 2008; 246:742753
37. Efstathopoulos EP, Kelekis NL, Pantos I, et al.
Reduction of the estimated radiation dose and associated patient risk with prospective ECG-gated
256-slice CT coronary angiography. Phys Med
Biol 2009; 54:52095222
38. Rubinshtein R, Halon DA, Gaspar T, Peled N,
Lewis BS. Cardiac computed tomographic angiography for risk stratification and prediction of
late cardiovascular outcome events in patients
with a chest pain syndrome. Int J Cardiol 2009;
137:108115

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