This article presents the evidence for coronary arterial calcium (CAC) screening as a predictor of coronary heart disease (CHD) and examines the characteristics of electron beam computed tomography (EBCT) that have improved CAC detection. Also, the authors discuss how the rapid technologic advances in helical CT are creating a challenge to EBCT’s role as the reference standard for CAC screening.
is an Associate Professor and
is a Professor at Roy J. and Lucille A. Carver College of
Medicine, Iowa City, IA.
Coronary heart disease (CHD) affects 1.6 million Americans each
year and accounts for approximately 500,000 deaths annually.
The pathogenesis of cardiovascular heart disease is complex, poorly
understood, and is related to a multitude of predisposing factors.
Even with a high aggregate risk for CHD, many individuals with
coronary artery disease (CAD) will not experience a "cardiac
event." Conversely, of those who experience a myocardial
infarction, only approximately 50% will have a history of CAD.
Despite the fact that the 8-year risk of CHD for the average
middle-aged person is only 1% to 5%, depending on risk factors, the
enormous costs of this disease (both in lives lost and healthcare
expenditures) makes the development of an effective screening
program extremely important.
The results of therapies specifically aimed at risk factors, such
as hypertension and hypercholesterolemia, have reduced the
mortality rates from heart disease.
Despite the enormous epidemiological efforts that target
risk-factor assessment and modification, risk-factors alone predict
only two-thirds of individuals who will eventually succumb to heart
Thus, there is a critical need to develop a simple, noninvasive
screening test that can provide an accurate assessment of the
presence and severity of CAD, while at the same time can predict
the individual risk for developing CHD.
In the last 11 years, there has been an explosion of interest
and associated scrutiny examining the clinical value of using the
presence of coronary arterial calcification (CAC) as a
prognosticator of CHD. Since CAC has been unequivocally shown to be
a marker of arteriosclerosis, considerable investigation has been
performed over the last decade, evaluating CAC detection and
quantification as a means to identify and predict those who are at
greatest risk for CHD. A great deal of this research has focused on
computed tomography (CT), specifically electron beam CT (EBCT),
producing evidence that EBCT has value as a valid screening tool
for CHD. Recently, the development of helical CT (HCT) technology
has refocused these research interests toward helical CT, assessing
its potential for CHD screening as well.
This article will briefly revisit the evidence for CAC screening
as a predictor of CHD and examine the unique characteristics of
EBCT that have established its superiority in CAC detection.
Additionally, the authors will discuss how the rapid technological
advances in HCT are creating a challenge to EBCT's role as the
reference standard for CAC screening.
The predictive "value" of coronary calcium
The presence of vascular calcification is an indisputable marker
for atherosclerosis. Furthermore, a strong correlation has been
identified between quantitative CAC measurements and pathologic
assessment of plaque volume and area.
Detection of CAC initially performed by conventional and digital
fluoroscopy subsequently identified an association between the
amount of CAC and CAD
and demonstrated a relationship between actual calcium mass
measurements and the measurements of the actual histologic
The presence of large and diffuse calcium deposits is also
associated with significant vascular narrowing on angiography on a
Coronary calcification, particularly when distributed over multiple
vessels, correlates with angiographic results, showing a high
sensitivity for atherosclerotic vascular disease (80% to 100%).
Coronary calcification serves as a strong predictor of significant
There is also a strong correlation between individual artery CAC
area measurements and plaque assessments determined by histology (r
Numerous studies have also repeatedly shown that extensive CAC,
particularly when distributed over multiple vessels, is associated
with significant coronary narrowing, correlates well with
angiography, and is also a predictor of patient outcomes.
Conversely, there is strong evidence that the absence of CAC, while
not excluding the presence of coronary atherosclerotic disease,
virtually excludes the likelihood of significant coronary arterial
stenosis (negative predictive values = 84% to 100%).
The specificity of CAC measurements for CAD is generally lower,
with reports ranging from 31% to 100%. No gender differences exist
between men and women.
While the presence of CAC as measured by calcium volumes and
scores are reflective of atherosclerosis, can such measurements
really be predictive of future coronary heart disease? Although the
development of CHD is unpredictable, autopsy studies have shown a
definite correlation between coronary calcium burden and the
frequency of myocardial infarction.
The causes of acute coronary occlusion due to atherosclerosis are
likely multifactorial. "Unstable" plaque configurations in
conjunction with localized inflammation probably act as a
Histologically, "soft plaques" (those with lipid cores and thin
fibrous caps) are believed to be at greatest risk for rupture and
subsequent vascular thrombosis.
It is postulated that soft plaques are more likely unstable and
prone to rupture, leading to acute cardiac syndromes, but that such
plaques are not necessarily associated with significant luminal
Occlusive coronary disease that arises from the rupture of
lipid-rich plaques occurs independent of plaque size or severity of
In fact, up to two-thirds of patients who have acute myocardial
infarction or unstable angina may have only minimal narrowing at
the site of the occlusion.
It is not clear if vascular calcium destabilizes plaques
facilitating rupture or whether this marker of plaque maturity
imparts plaque stability.
It is known, however, that hard and soft plaques coexist in similar
Therefore, the quantification of calcified plaques could serve as a
surrogate measurement of the number of soft plaques.
Thus, it seems logical to assume that CAC could be useful as one
determinate to establish individual relative risk for CHD.
There is growing consensus that the risk of developing CHD can
be stratified according to CAC volume, with greater risk ascribed
to those with extensive, multivessel disease. Quantitative CAC
measurements by EBCT have shown that as CAC increases so does the
likelihood of coronary heart disease.
Patients with EBCT calcium scores above the median (>75) were
found to be six times more likely to experience a cardiac event,
such as myocardial infarction and sudden cardiac death.
Arad et al
demonstrated that individuals with calcium scores >160 were 35
times more likely to experience a cardiovascular event and that CAC
was more predictive of such events than other traditional risk
factors. For coronary artery calcium score thresholds of 100, 160,
and 680, the sensitivities of EBCT for cardiac events were 89%,
89%, and 50%, while the specificities were 77%, 82%, and 95%,
respectively. Ultimately, such observations have served as the
foundation for the establishment
of CAC quantification by CT as a valid useful screening exam for
These investigators, among many others, were instrumental in
developing EBCT imaging standards that have become universally
applied by many investigators and screening centers around the
Technical advantages of EBCT
The unique design of EBCT affords significant advantages over
conventional CT for cardiac imaging. Having no moving parts, EBCT
is capable of providing 50-msec image acquisition times. Coupled
with prospective electrocardiogram (ECG) gating, EBCT can provide
near real-time cross-sectional imaging of the beating heart.
Possessing excellent spatial and temporal resolution, EBCT is
considered by many as the reference standard in providing cardiac
analysis, and, particularly, CAC quantification.
EBCT imaging protocol
Standard imaging protocol for EBCT CAC screening encompasses
single breath-hold neutral axis imaging with prospective ECG
gating. Implementing a 60% to 80% R-REKG interval (R-R) interval
trigger point, coupled with superb temporal resolution, EBCT can
provide reproducible diastolic image sets of the heart that are
critical to CAC quantification. In the volume mode sequence (3-mm
slice thickness at 100 msec/slice), EBCT can produce 80 images of
the heart with a nominal pixel size of 0.68 mm
(35-cm reconstruction circle) (Figure 1). To optimize temporal and
Z-axis spatial resolution, a complete data set can usually be
acquired with one breath. The examination time is usually <15
minutes, delivering <2.6 mSv of radiation for a complete
coronary calcium study. This would equate to approximately 10.4
months of background radiation to the general public.
Several proprietary software packages enable operators to
quickly detect and perform quantitative CAC measurements for all
major coronary arteries. Aggregate calcium burden is usually
reported as a calcium score that can be compared with normalized
data according to age- and gender-matched controls.
While scoring packages allow independent manipulation of threshold
criteria, most centers default to the scoring protocol established
by Agatson et al.
However, increasing emphasis is being placed on the volume score,
rather than on the calcium score, as a measurement of CAC
The inter- and intra-observer variabilities of EBCT CAC
measurements are excellent.
Poorer inter-study variability exists, particularly with the
identification of smaller foci of calcium.
This variability largely stems from slice misregistration due to
cardiac motion. This problem has been largely rectified by
manipulating threshold area or slice thickness and/or by averaging
the CT density measurements of lesions (rather than using peak
density of calcium deposits) to calculate calcium scores.
Other solutions that have improved examination reproducibility have
been achieved by implementing postprocessing.
Similarly, averaging scores from duplicate scans has improved
reproducibility and is now becoming common practice at many
screening sites. Shields et al
reported a reliability of 0.99 in 50 subjects who underwent dual
Hernigou et al
reported an inter-examination error rate of 7.2%.
Since EBCT is considered the reference standard for imaging of
coronary calcium, how does HCT compare? Due to a host of very
significant technologic advances in recent years, the performance
of HCT in CAC quantification is quickly approaching that achieved
with EBCT. The most significant of these developments relate to
faster image acquisition times, use of multislice systems, and
institution of ECG gating. Just in the past 3 years, image
acquisition times have decreased from 1 sec to 500 msec,
significantly enhancing temporal resolution, image quality and scan
reproducibility (Figures 2A and B). Half-scan techniques in the
sequential single-slice mode have decreased imaging time from 320
msec to 125 msec. Like EBCT, HCT allows examinations to be
performed using single breath-hold sequences, thereby improving Z
axis resolution. Inherent advantages in image efficiency have also
been realized with the introduction of multislice scanning
protocols that provide greater Z axis coverage per revolution,
further decreasing examination time and decreasing problems with
The ability to acquire a true diastolic image data set has
become a reality with development software that provides
prospective ECG gating. The significance of this development has
remedied a significant shortcoming of HCT--previously, nongated
acquisitions that were prone to significant volume averaging and
slice misregistration errors resulted in divergent CAC measurements
as compared with EBCT.
Gated acquisitions can be performed operating in the sequential
(single-slice) mode or helical acquisition mode, and can be
obtained either prospectively (similar to EBCT) or retrospectively.
The latter requires postprocessing of the entire data set, allowing
operators to select diastolic images individually for analysis.
Since retrospective ECG-gated studies are associated with large
data sets, there is a concomitant increase in total radiation dose
as well as additional time requirements to perform postprocessing
image analysis (Table 1).
Prospective ECG gating closely resembles an EBCT acquisition,
choosing a triggering point at peak diastole (usually 60% to 80% of
the R-R interval). Compared with retrospective gating, this mode
represents a targeted, smaller data set with an associated decrease
in total radiation dose. Unfortunately, prospective gated
sequential acquisitions require longer examination times to allow
for table movement to occur. This, in turn, often requires two
acquisitions to complete a study, potentially introducing breathing
and slice misregistration artifacts. Compared with multislice
acquisitions that can examine the heart in larger tissue volumes,
the sequential gated acquisitions, in reality, are associated with
less artifact degradation and tend to provide CAC scores that more
closely approximate EBCT measurements.
Regardless, the development and institution of ECG gating has
significantly improved image quality (Figure 2) and calcium score
variability compared with traditional nongated acquisitions.
Early investigations that compareCAC measurements of EBCT and
HCT show that both now possess comparable performance in image
quality and CAC quantification. Reproducibility correlation
coefficients reported by several investigators are also excellent
(r = .95 to .99).
Preliminary evidence also shows that helical CAC measurements, like
EBCT, correlate well with angiography with regard to accuracy and
predictive values for CAD.
Broderick et al,
using two scoring methods for HCT, reported sensitivities and
specificities of 81% to 88% and 52% to 61%, respectively, as
compared with obstructive disease by angiography. There was no
significant difference between contiguous slice acquisitions and
overlapping slice (volumetric) acquisitions.
Like EBCT, negative HCT scans appear to have high
negative-predictive values for CAD compared with angiography
(specificity 100%; sensitivity 61%; accuracy 85%).
With significant advancements in hardware design and software
technology, HCT technology has made great progress in removing many
of the hurdles that initially limited its CAC screening capability,
as compared with EBCT. At this time, preliminary data is beginning
to demonstrate comparable performances for both modalities. Unlike
EBCT, where the technology is mature and additional refinements
unlikely, helical technology will continue to undergo further
refinements, such as expansion of multislice configurations. This
will, in turn, provide additional improvements in spatial
resolution and will decrease examination times. Considering the
popularity and widespread availability of spiral scanners, these
inevitable refinements portend a future in which HCT will likely
assume a pre-eminent role in CAC detection and quantification.