cardiology education

1. REVIEW ARTICLE
Characterizing stable coronary plaques with MSCT
angiography
C. Van Mieghem
Department of Cardiology, OLV Hospital, Aalst, Belgium
Keywords
Atherosclerosis, coronary plaque, multislice
computed coronary angiography
Correspondence
C. Van Mieghem, Department of Cardiology,
OLV Hospital, Moorselbaan 164, Aalst,
Belgium. Tel: +32 53 728884; Fax: +32 53
724587; E-mail: carlos.van.mieghem@olvz-
aalst.be
Funding Information
No funding information provided.
Continuing Cardiology Education, 2016;
2(2), doi: 10.1002/cce2.28
Abstract
Noninvasive access to coronary anatomy has long been anticipated and eventu-
ally became available with the emergence of multislice computed tomography
angiography (MSCTA). MSCTA offers the possibility to identify coronary artery
disease already in its preclinical phase. This unprecedented information proves
to be useful in clinical practice as it allows the appropriate allocation of preven-
tive therapies such as statin and aspirin.
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Introduction
Cardiac imaging is at the cornerstone of diagnosis, prog-
nostic stratification, and treatment of virtually all cardio-
vascular diseases and, specifically, coronary artery disease
(CAD). Noninvasive access to coronary anatomy has long
been anticipated and eventually became available with the
emergence of multislice computed tomography angiogra-
phy (MSCTA). The diagnostic accuracy and prognostic
utility of MSCTA when assessing for the presence of ana-
tomic CAD has been well examined [1, 2]. Three prospec-
tive multicenter studies have demonstrated MSCTA,
compared with invasive coronary angiography (ICA) as
the reference standard, to have exceptional sensitivity and
moderate specificity for CAD detection and exclusion [1,
3, 4]. Of perhaps equal importance, MSCTA identifies
the presence of CAD at a preclinical stage in “healthy”
subjects.
Detection and Characterizing
Coronary Plaques by MSCTA
With the advent of MSCTA, coronary anatomy and the
presence of atherosclerosis can be directly imaged
noninvasively. Coronary atherosclerosis can be either
nonobstructive due to arterial wall compensatory remodel-
ing or may impact on the coronary lumen (Figure 1).
MSCTA allows to assess the extent, severity, and localiza-
tion of coronary plaques [5–9]. Furthermore, the CT scan-
ner distinguishes the various components of coronary
plaques as they have different X-ray density values. Lipid
and fibrous tissue are low-density structures and calcium
is a high-density structure, whereas a very low-density
obstruction in the setting of an acute coronary syndrome
may represent a thrombotic occlusion. When assessing car-
otid artery plaques in patients who underwent carotid
endarterectomy, the CT attenuation value, expressed in
Hounsfield units (HU), of lipid tissue (39 Æ 12 HU) is
distinctly lower than the attenuation value of fibrous tissue
(90 Æ 24 HU) [10]. The distinction between lipid and
fibrous plaques is also feasible in the larger segments of
coronary arteries, provided that the imaging conditions are
optimal and with the caveat of using intravascular ultra-
sound (IVUS) as the reference standard instead of histo-
logical specimens [11]. In the real world, the density values
of fibrous and lipid plaques overlap significantly, which
makes the assessment of the individual noncalcified plaque
components in the coronary tree much less reliable [12].
ª 2016 Hellenic College of Cardiology Continuing Cardiology Education, doi: 10.1002/cce2.28 (99 of 104)
Continuing Cardiology Education

2. Coronary calcifications can be easily detected with car-
diac CT, because of the high radiation absorption coeffi-
cient of calcium. Coronary calcification is an active
process and the development of coronary artery calcifica-
tion is intimately associated with the development of
coronary atherosclerotic plaques [13, 14]. Calcification
does not occur in the wall of normal coronary arteries
and the presence of coronary calcification is pathog-
nomonic for the presence of coronary atherosclerosis
[15]. The presence of coronary calcification is associated
with coronary plaque size. However, not all plaques are
calcified: in a histological study, the total calcium area
was approximately only 20% of the total atherosclerotic
plaque burden [16].
Calcification of the coronary arteries was already docu-
mented many years ago by early electron beam computed
tomography (EBCT) [17]. Coronary calcium deposits
have a high X-ray density which is approximately 2–10
fold higher than the low-density adjacent noncalcified tis-
sue and surrounding fat tissue. Agatston et al. developed
a calcium scoring algorithm for CT images that is now
widely used in research and clinical practice (Figure 2)
[18]. The calcium score is derived from the product of
the area of calcification (expressed in square millimeters)
and a factor determined by the maximal X-ray density
within that area. The total Agatston score results from
adding up the scores for all individual calcific lesions.
Alternative quantification methods include assessment of
the calcified volume and the mass of calcium. These
newer quantification methods have better reproducibility
as compared to the traditional scoring method by Agat-
ston [19, 20]. They are, however, seldomly used, as nearly
all reported studies are based on the “Agatston” score.
The prevalence of coronary calcium is strongly related
to age, with sharply increasing prevalences after age 50 in
men and age 60 in women. At the ages of 65–70, the
prevalences are almost equal [21]. The extent of coronary
calcification, expressed in Agatston score, is larger in men
than in women and in persons with diabetes or insulin
resistance as compared to those without diabetes or insu-
lin resistance [22, 23].
Rationale and Clinical Implications of
Coronary Plaque Imaging with
MSCTA
For a long time, only ICA was available to provide access
to coronary anatomy and to evaluate for the presence of
(A) (B)
Figure 2. Calcium scoring scan: examples of a scan with a high amount of calcium (A) and no calcium (B).
(A) (B) (C)
Figure 1. CT images of a normal left coronary artery (A), non-obstructive plaque (arrowhead) in the distal left main coronary artery (B) and
extensive calcified and non-calcified atherosclerosis (arrowheads) with significant lumen narrowing in the left main coronary artery and left
anterior descending artery (C).
Continuing Cardiology Education, doi: 10.1002/cce2.28 (100 of 104) ª 2016 Hellenic College of Cardiology
MSCT angiography in stable CAD C. Van Mieghem

3. CAD. Due to biological factors (mainly arterial remodel-
ing) and the methodological limitations of a contour
method, ICA underestimates both the extent and severity
of atherosclerosis [24]. IVUS is a reliable technique to
study both the morphologic changes of the coronary ves-
sel wall as well as the degree of luminal encroachment.
When analyzing patients affected by CAD with MSCTA,
IVUS, and ICA, early coronary plaque formation is reli-
ably detected by MSCTA and often remains “silent” on
ICA [25, 26]. While other noninvasive tests focus on the
physiological consequences of coronary obstruction,
MSCTA represents anatomic disease itself (Figure 3) [27].
As a result, MSCTA offers the possibility to screen sub-
jects for preclinical CAD. It is conceptually appealing to
believe that these subjects are at higher risk than their
asymptomatic counterparts who have no coronary plaque
and a normal or low calcium score. Large studies with
prospective prognostic data have indeed demonstrated
that the quantification of coronary calcifications using the
Agatston score can be used as a tool to predict the risk
of future cardiovascular events and all-cause mortality
[28–31]. There is generally a strong consistency between
increased coronary artery calcium (CAC) score and risk
of cardiovascular events. The absence of CAC is associ-
ated with low annual event rates of between 0.06% and
0.11% [32, 33]. The relative risk in asymptomatic individ-
uals with high CAC burden seems to be significant, with
relative risk up to 26 times in subjects with a CAC score
of greater than 400 compared with subjects with no CAC
[29]. For very high scores of 1000 or greater, the risk of
myocardial infarction or coronary death within 1 year
was as high as 25% [34].
It is common practice to risk stratify asymptomatic
individuals using risk factor models such as the Framing-
ham or European Society of Cardiology scoring systems
[35, 36]. Asymptomatic individuals can be categorized
into three levels of risk. Individuals considered to be at
high risk are defined as having a Framingham risk of
20% or more (SCORE risk of 5% or more) of a coronary
event within 10 years. It is estimated that approximately
25% of adults fall into this category. Intermediate risk
is defined as a Framingham risk of a coronary event of
10–20% (SCORE risk between 1% and 5%) within
10 years, and about 40% of adults over 20 years of age
fall into this category. Low risk is defined as a Framing-
ham risk of a coronary event within 10 years of less than
10% (SCORE risk lower than 1%). About 35% of adults
over 20 years of age have low risk.
The benefit of the CAC score lies in its potential to
add incremental information for the prediction of coro-
nary events and mortality beyond traditional risk factors
(Table 1) [29, 31, 37, 38]. Based on American and Euro-
pean guidelines, it is reasonable to consider the use of a
calcium scan in an intermediate-risk group of individuals
as the outcome of the calcium scan can influence clinical
decision making in this selected group [36, 39]. Such
individuals might be reclassified to a higher group risk
Figure 3. Overview of noninvasive and invasive tests available for the
evaluation of patients with coronary atherosclerosis. The noninvasive
tests are usually designed to detect the physiologic effects of (flow-
limiting) coronary stenoses on myocardial perfusion. MSCTA allows
for direct visualization of coronary plaques, often in early stages of
the disease. Such plaques frequently develop in coronary segments
with positive remodeling (from “The dawn of a new era–noninvasive
coronary imaging1996 Apr;21(2):75-7 Erbel R. Herz.,” with
permission of Springer)
Table 1. C-statistic with coronary risk factors and with the addition of coronary artery calcium. Data from references [29, 31, 37, 38]
Study, Year
No. of
participants
Follow-up
(years)
C-statistic with
risk factors
C-statistic with
coronary artery
calcium P-value
St Francis Heart Study, 2005 4903 4.3 0.69 0.79 0.0006
Budoff et al., 2007 25.253 6.8 0.611 0.813 <0.0001
Becker et al., 2008 716 8.1 0.68 0.77 <0.01
Multi-ethnic study of
atherosclerosis, 2012
6722 3.8 0.623 0.784 <0.001
Recall, 2009 4814 5 0.667 0.754 0.0001
ª 2016 Hellenic College of Cardiology Continuing Cardiology Education, doi: 10.1002/cce2.28 (101 of 104)
C. Van Mieghem MSCT angiography in stable CAD

4. status based on high CAC score, and subsequent manage-
ment may be modified (Figure 4). The demonstration of
the early stages of CAD by means of MSCTA may prove
to be a valuable tool for the appropriate allocation of pre-
ventive therapies such as statins and aspirin. In a recent
study, statin therapy was associated with a significantly
lower mortality for individuals with atherosclerotic plaque
on MSCTA, but not for individuals with normal coronary
arteries [40].
Conclusions
Coronary anatomy used to be accessible only through
invasive catheterization. With the emergence of MSCTA,
it has become possible to screen subjects while the
atherosclerotic disease is still at a preclinical stage.
Atherosclerosis imaging using MSCTA helps to refine risk
assessment built on the knowledge of the individual’s
burden of atherosclerosis. Clinical data are becoming
available showing the efficacy of targeted preventive thera-
pies, such as the effective use of statins in asymptomatic
individuals with evidence of CAD but not in those with-
out signs of CAD.
Conflict of Interest
Dr. Van Mieghem has nothing to disclose.
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MSCT angiography in stable CAD C. Van Mieghem