Cardiovascular Diseases and Internal Medicine,
Mayo Clinic,
Rochester, Minn
To the Editors:
I read with enthusiasm the recent article by Secci et
al.1 This prospective study using electron beam
CT (EBCT) and coronary calcium score was done in 326 mostly
elderly (mean age, 66±8 years) men (82%). Hypertension (50%) and
family history of coronary disease (44%) were common, but
lipids were average (LDL 144±37 mg/dL, HDL 54±14 mg/dL). The 10-year
Framingham risk was 19±9%. Each was followed up for 32 months after
EBCT or until documentation of a hard (death, infarction) or a soft
(need for revascularization) event. Dividing
results into quartiles of EBCT calcium score, Secci et al found a clear
trend for more total events in those with scores above the median. When
hard and soft events were separated, there were still significantly
more soft events when the score was above the median. However, despite
a greater total number of events for subjects with calcium scores in
the highest quartile, especially compared with those with scores in the
lowest quartile, there was no significant trend for hard events
alone.
My comments relate to four important issues not raised in the
discussion. First, the amount of calcified plaque correlates, albeit as
an underestimation, with the total atherosclerotic plaque burden
(lipid-rich, fibrotic, and calcified fibrotic plaques) as shown by
histological2 3 and
ultrasonic4 5 studies. The discussion by Secci et
al of calcified plaque and acute coronary syndromes totally
misses the point regarding total plaque burden and vulnerable plaques,
calcification, and inflammation.6 Second, the
data7 given in their reference 16 states an
average 10-year risk for men between 60 and 70 years old of 21% to
30%. This would suggest that the cohort currently under discussion was
likely average and not necessarily high risk, since age and male gender
are particularly important determinants using the Framingham equations.
In fact, the calcium scores given in Table 3 of the Secci study (3-mm
protocol) are similar to those previously published in similar age
groups by Janowitz for "average" asymptomatic
adults.8 Third, the study is significantly
underpowered (n=326) for hard cardiac events, and from the outset, a
potentially weak but not necessarily significant relationship to
calcium score would have been anticipated. By combining hard and soft
events, they likely improved the power and were able to demonstrate a
correlation to higher calcium scores (above the median and especially
in the highest quartile). Fourth, the follow-up was actually short,
less than 3 years, and arbitrary at best. Follow-up of a minimum of 5
years is the common time period for most prospective studies examining
cardiac events. They need to continue follow-up for a more extended
time period. Rather than decrying this as such a "negative" study,
I find the results provocative, consistent with
prior studies9 10 11 in younger adults, and
supportive of the notion that the EBCT calcium score, as a surrogate to
total atherosclerotic plaque burden and thus extent of coronary
disease, has the potential to become one of the most if not the most
powerful noninvasive predictors of cardiac mortality and morbidity in
adults at risk, irrespective of age and gender.
References
1.
Secci A, Wong N, Tang W, Wang S, Doherty T,
Detrano R. Electron beam computed tomographic coronary calcium
as a predictor of coronary events: comparison of two protocols.
Circulation. 1997;96:1122–1129.
2.
Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF,
Schwartz RS. Coronary artery calcium areas by electron beam
computed tomography and coronary atherosclerotic plaque area: a
histopathologic correlative study. Circulation. 1995;92:2157–2162.
3.
Mautner SL, Mautner GC, Froehlich J, Feuerstein IM,
Proschan MA, Roberts WC, Doppman JL. Coronary artery disease:
prediction with in vitro electron beam CT. Radiology. 1994;192:625–630.
4.
Mintz GS, Pichard AD, Popma JJ, Kent KM, Satler LF,
Bucher TA, Leon MB. Determinants and correlates of target lesion
calcium in coronary artery disease: a clinical, angiographic
and intravascular ultrasound study. J Am Coll Cardiol. 1997;29:268–274.[Abstract]
5.
Baumgart D, Schmermund A, Goerge G, Haude M, Ge J,
Adamzik M, Sehnert C, Altmaier K, Groenemeyer D, Seibel R, Erbel R.
Comparison of electron beam computed tomography with
intracoronary ultrasound and coronary angiography for
detection of coronary atherosclerosis.
J Am Coll Cardiol. 1997;30:57–64.[Abstract]
6.
Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL,
Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic
mechanisms—oxidation, inflammation, and genetics.
Circulation. 1995;91:2488–2496.
7.
Anderson K, Wilson P, Odell P, Kannel W. An updated
coronary risk profile. Circulation. 1991;83:356–363.
8.
Janowitz WR, Agatston AS, Kaplan G, Viamonte M.
Differences in prevalence and extent of coronary artery calcium
detected by ultrafast computed tomography in asymptomatic
men and women. Am J Cardiol. 1993;72:247–254.[Medline]
[Order article via Infotrieve]
9.
Detrano R, Tzung H, Wang S, Puentes G, Fallavollita J,
Shields P, Stanford W, Wolfkiel C, Georgiou D, Budoff M, Reed J.
Prognostic value of coronary calcification and angiographic
stenoses in patients undergoing coronary angiography.
J Am Coll Cardiol. 1996;27:285–290.[Abstract]
10.
Arad Y, Spadaro LA, Goodman K, Liedo-Perez A, Sherman
S, Lerner G, Guerci AD. Predictive value of electron beam computed
tomography of the coronary arteries: 19-month follow-up of 1173
asymptomatic subjects. Circulation. 1996;93:1951–1953.
11.
Agatston AS, Janowitz WR, Kaplan GS, Lee D, Prashad R,
Viamonte M, Lamas GA. Electron beam CT coronary calcium
predicts future coronary events. Circulation.
1996;94(suppl I):I-360. Abstract.
Harbor-UCLA Medical Center,
Torrance, Calif
Rumberger responds to our report entitled "Electron Beam
Computed Tomographic Coronary Calcium as a Predictor of
Coronary Events: Comparison of Two Protocols." This report
treated a preliminary study of the 326 members of our South Bay Heart
Watch cohort of 1309 high-risk subjects. These 326 subjects were
scanned multiple times using two different electron beam CT scanning
protocols within a half-hour period in 1991. All 1309 subjects have now
been followed up clinically for 3 years. The preliminary report to
which Rumberger refers states three conclusions:
1. Calcium quantities from the 3-mm and more reproducible 6-mm scans
are equally accurate for predicting coronary events.
2. Calcium is a weak predictor of coronary death and
infarction.
3. The predictive accuracy of calcium for predicting
revascularization is greater than that for
predicting death or infarction.
Rumberger does not disagree with our conclusions but comments on their
interpretation in our discussion. Specifically, he states that we
"missed the point" regarding the monotonically increasing
relationship between the amount of calcified plaque and the "total
plaque burden" that he and others have noted in autopsied hearts.
We agree that the amount of calcific plaque, quantitated on
radiographic studies, roughly reflects the total sum of
atherosclerotic areas in segments of the coronary tree.
However, what determines the probability of a coronary
catastrophe is not only the amount of atherosclerosis
but the propensity of individual plaque segments to rupture and collect
blood elements that obstruct the arterial lumen.
The following mathematical diversion clarifies this point.
Here, P(t) denotes the probability of plaque rupture somewhere in the
coronary tree at time t, and dl is an infinitesimal segment
length in that tree. P(t) will be related to the plaque areas as
follows:
The argument between the integral sign and dl is a product
of two factors. The plaque area, A(l,t), changes with location, l, in
the coronary tree and also changes with time (progresses). This
plaque area is what Rumberger has found to be roughly and directly
related to the amount of calcium. The second factor in the argument,
p(l,t), is the plaque vulnerability function. This is the probability
that plaque at location l will rupture at time t. This probability
increases with the size of the lipid core.1 It
decreases with the thickness of the fibrous cap1
and probably with the amount of calcium deposited in the
plaque.2 Thus, this factor will contribute to an
inverse relationship between the probability of coronary death
or infarction and the measured amount of calcification.
Cities are occasionally buried by volcanic eruptions. The chance that a
city will be buried depends not only on the number of nearby peaks but
also on the volcanic activity of each one. Indeed, Vesuvius is the only
large mountain near Pompeii.
These considerations explain why calcification, even if it correlated
perfectly with the quantity of atherosclerosis, might
not be a good predictor of coronary events. The relation
between the amount of calcium and the probability of coronary
events is much more complex than we might have desired.
Rumberger believes that as the power of our study grows with time and
with the inclusion of all subjects in the cohort, we will see a
relationship between coronary calcium amount and hard events.
Indeed, we agree and have already seen this
relationship.3 However, the relationship remains,
as Rumberger has supposed, "weak." In fact, the discriminatory
power of coronary calcium remains similar to that of the serum
cholesterol, which is cheaper to obtain and can be
modified.
References
1.
Mann J, Davies M. Vulnerable plaque: relation of
characteristics to degree of stenosis in human coronary
arteries. Circulation. 1996;94:928–931.
2.
Cheng GC, Loree HM, Kamm RD, Fishbein MC, Lee RT.
Distribution of circumferential stress in ruptured and stable
atherosclerotic lesions: structural analysis with
histopathological correlation. Circulation. 1993;87:1179–1187.
3.
Detrano R, Wong ND, Tang W, Doherty TM. Determining
coronary event risk in asymptomatic high risk
subjects: a risk factor versus an anatomic approach.
Circulation. 1997;96(suppl):I-404. Abstract.
© 1998 American Heart Association, Inc.
Correspondence
Electron Beam CT and Coronary Calcium Score
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