Computed tomography (CT) can easily detect coronary calcifications, and allows for a fast and noninvasive assessment of coronary atherosclerosis. This article reviews the use of electron beam (EBCT) versus helical CT for coronary imaging, including the evaluation of symptomatic patients with atypical chest pain to rule out CAD, as well as the investigation of asymptomatic patients to predict the risk of future cardiac events and to follow the effectiveness of risk-factor modification.
is an Associate Professor and the Section Chief of Body CT,
Department of Clinical Radiology, University Hospital Munich,
In the United States, there are 1.5 million heart attacks
annually and 1 of 2 adults dies from heart and vascular disease.
The leading cause of unheralded heart attacks is rupture of
vulnerable atherosclerotic plaques, resulting in thrombosis and
sudden coronary occlusion. However, many more of the pre-existing
vulnerable atherosclerotic lesions are in nonstenotic rather than
in stenotic coronary artery segments and, therefore, do not cause
any symptoms prior to an event.
Because of this fact, vulnerable plaques may not be reliably
assessed by coronary angiography or by electrocardiogram (ECG)
stress testing. Noninvasive ultrasound and Doppler are able to
assess atherosclerosis in several different arterial vessel regions
but not in the coronary arteries. With computed tomography (CT),
coronary calcifications can be detected easily; therefore, it
allows for a fast and noninvasive assessment of coronary
Histopathology of coronary calcium
The presence of arterial calcifications is specific for
atherosclerosis. In rare cases (eg, hypervitaminosis D,
Mönckeberg's sclerosis, and infantile calcifications), vessel
calcifications may mimic classical atherosclerotic calcifications.
In classical atherosclerotic lesions, precipitates of calcium
phosphate develop between the intimal and medial layers of the
vessel wall by mechanisms similar to those known from
osteoneogenesis. From the pathologic point of view, vascular
calcifications are found in fibroatheromas, an advanced and
nonreversible stage of atherosclerosis.
From the clinical point of view, coronary artery calcifications
correlate neither with the site nor with the degree of coronary
artery disease (CAD) with vessel stenoses and myocardial ischemia.
Coronary calcium and coronary artery disease
Agatston et al
first reported the detection of coronary calcifications by electron
beam CT (EBCT). They investigated 475 patients with CAD and 109
patients without CAD by EBCT as well as by fluoroscopy, and divided
the patients into different age groups (30 to 39, 40 to 49, 50 to
59, 60 to 69 years). In every patient, a scan of the first 60 mm of
the heart was acquired, with 3-mm consecutive slices in a
breath-hold period of 30 seconds. To reduce cardiac motion
artifacts, the images were acquired with prospective ECG triggering
and exposure time of 100 milliseconds. To distinguish between
coronary calcification and noise in EBCT images, a threshold of 130
Hounsfield units (HU) was used. Fluoroscopy and EBCT detected
coronary calcifications in 90% and 52% of patients, respectively.
Every plaque in the EBCT images was ranked by its HU density (1 =
130 to 199 HU, 2 = 200 to 299 HU, 3 = 300 to 399 HU, 4 = >= 400
HU) and multiplied by the area of the plaque. A score for every
patient was determined by the sum of all plaque numbers. They
reported that the score in every age group was significantly
different in patients with and without CAD.
When scanning for coronary calcifications became more popular,
the American Heart Association released guidelines for coronary
According to these guidelines, there is no indication for screening
symptomatic patients with obvious myocardial ischemia. Coronary
screening may be indicated only for symptomatic patients with
atypical chest pain, for asymptomatic patients with cardiovascular
risk factors, and for a follow-up investigation in patients under
Laudon et al
demonstrated that in patients presenting to an emergency department
with atypical complaints, the exclusion of coronary calcifications
by EBCT has a high negative predictive value (95% to 98%) in ruling
out CAD. If coronary calcifications are present, these patients
still require further investigations, such as ECG stress testing.
In younger patients suffering from atypical chest pain, coronary
calcifications may be a rare finding, and therefore EBCT fails to
rule out CAD. These patients may have noncalcified plaques only,
resulting in coronary artery stenoses. Therefore, in our
institution, we have decided to perform CT angiography in any
symptomatic patient to investigate calcified, as well as
Coronary calcium and future cardiac events
Conventional risk-factor assessment can help to predict the risk
for future cardiac events in a cohort population, but not in the
individual patient. The most challenging aspect of the detection of
coronary calcification by CT may be the ability to predict cardiac
events in each asymptomatic patient. Arad et al
followed 1173 asymptomatic patients over a 19-month period. In this
patient population, they observed 26 soft (revascularization and
bypass grafting) and hard (myocardial infarction and death) events
in 18 patients. On the base of the data collected, an odds ratio of
35.4 was calculated for a cardiac event in patients with a score
Raggi et al
published score percentiles on the base of 9728 patients
investigated with an EBCT. In a control group study of 172 patients
with myocardial infarction and 632 without, they found that 70% of
all events took place in patients who were above the 75
Wong et al
followed 928 asymptomatic patients over a period of 3.3 years and
observed 28 soft and hard events. Patients were assigned to the 4
quartile if they were above the 75
score percentile from 21,000 patients (relative ranking) or above
the score of 105 (absolute ranking). They found that the odds ratio
was not significantly different between the relative and absolute
ranking (6.02 and 6.37, respectively). Because of the ease of use,
we perform absolute ranking for risk stratification in asymptomatic
All of the currently available literature on the predictive
value of coronary calcium is limited by many different factors.
Most of the patients enrolled in these studies were not randomized
but self-referred; many of the patients were aware of their scan
results and may have changed their lifestyle accordingly; the study
end points were coronary revascularization and bypass grafting
instead of only hard events.
trials are prospective randomized cohort studies with patients who
are unaware of their scan results and use hard events only as the
final end point. They will enroll a total of more than 10,000
patients to prove the hypotheses that coronary calcifications have
a predictive value for hard events independent of, and superior to,
conventional risk-factor assessment. The final results of these
trials will be available no earlier than 2010.
Progression of coronary calcium
Callister et al
reported that the traditional scoring algorithm is inappropriate
for following the progression of coronary calcifications over time.
Therefore, he introduced the volume calcium measurement from EBCT
images and followed 149 asymptomatic patients over a period of 12
to 15 months.
A total of 65 patients with a mean low-density lipoprotein (LDL)
<120 mg/dL and 40 patients with a mean LDL >120 mg/dL
received lipid-lowering medication. The remaining 44 patients
presented with a mean LDL >120 mg/dL and did not receive any
medication. The effectively treated patient group demonstrated a 7%
regression in calcium volume, while the noneffectively treated
patient group had a moderate progression of 25% of the calcium
volume. A mean progression rate of 52% was found in the nontreated
control group. It should be emphasized that the variability of a
repeated coronary calcification measurement with EBCT is >10%
and a regression of coronary calcifications is very unlikely from
the pathologic point of view.
Coronary calcium with multidetector row CT
We were able to demonstrate that conventional CT is as sensitive
as EBCT in detecting coronary calcifications.
Adjusting conventional CT scan parameters to acquire image quality
similar to EBCT also allows for determination of the traditional
However, the score originally defined by Agatston et al
is a dedicated semiquantitative quantification algorithm designed
for the EBCT and it is difficult to reproduce by conventional CT
when scan parameters are changed.
After helical scanning with multi-detector row CT (MDCT),
retrospective ECG gating with overlapping incremental
reconstruction is performed to improve reproducibility of the
calcium measurement. Multiplying the area, slice increment, and
HU-density allows for the determination of the mass equivalent of
calcified plaques in MDCT images. Using a phantom with calcium
inserts of known mass allows for determination of a calibration
factor for different MDCT scan protocols.
Multiplying the mass equivalent by the calibration factor
obtained from the calibration phantom results in the absolute mass
of coronary calcifications in milligrams of calcium hydroxy-apatite
(mg CaHA). Multidetector row CT is able to detect coronary
calcification with a sensitivity of 1 mg CaHA. In patients with
extensive coronary calcifications, a calcium mass of more than 1.5
g CaHA may be found.
The traditional score is approximately 5 times higher than the
calcium mass. Only with the calibrated mass measurement, however,
can MDCT scan protocols be modified with the same results. For
example, we found that the absorption for coronary calcium is
higher, at 80 kV compared with 120 kV. Using 80 kV instead 120 kV
allows reduction of radiation for screening by 30% without loss of
information. Changing the tube voltage will influence the density
of plaques and therefore the traditional score. The calibrated
calcium mass, however, will remain the same with both CT
We still follow the recommendations of the American Heart
Association with the following modifications.
Patients with unstable angina tend to have fewer calcified
plaques, but more noncalcified plaques, than patients with stable
angina. In younger symptomatic patients, noncalcified lesions may
be present even in the absence of any calcified lesions. For
example, in a patient with atypical chest pain, we observed a
noncalcified plaque with a low density (20 HU) that seemed to
correspond to an intracoronary thrombus.
Therefore, we decided to perform a contrast-enhanced MDCT
angiography in any symptomatic patient referred for CT
investigation of the coronary arteries.
In asymptomatic patients, we first perform nonenhanced CT
studies of the coronary arteries. In cases in which no
calcifications are present, we do not recommend any treatment and
simply reassure these patients of their low-risk. In asymptomatic
patients with a positive coronary calcium scan and a calcium mass
<20 mg CaHA (traditional score of 100), we recommend that
patients modify their cardiovascular risk factors and follow the
progression of the calcifications within the next 5 years. If the
amount of coronary calcium exceeds 20 mg CaHA, we recommend
performing further testing for CAD. We never recommend performing a
cardiac catheter investigation on the basis of an unenhanced
coronary CT investigation alone.
However, neither the presence nor the amount of coronary calcium
accurately reflects the extent of coronary atherosclerosis. In
asymptomatic patients, contrast-enhanced CT angiography can detect
calcified as well as noncalcified lesions. We have found that
noncalcified lesions with low CT densities (40 HU) may correspond
to lipid-rich plaques (atheromas), which are more prone to rupture
and to cause an acute event than are plaques with high CT densities
(90 HU) that more likely contain fibrotic tissue
Currently, many MDCT scanners are widely available. Since we
have shown that MDCT is as feasible as EBCT for the detection and
quantification of coronary calcifications, non-invasive assessment
of coronary atherosclerosis is no longer limited to special centers
with an EBCT scanner. Current clinical applications of coronary
MDCT may include the evaluation of symptomatic patients with
atypical chest pain to rule out CAD, as well as the investigation
of asymptomatic patients to predict the risk of future cardiac
events and to follow the effectiveness of risk-factor modification.
Assessment of coronary atherosclerosis and CAD may further improve
with the use of contrast-enhanced MDCT studies.