PERSPE C T I V E
Interpreting the Coronary-Artery Calcium Score
Paul A. Grayburn, M.D.
A 55-year-old white man pre-
sented with an abnormal
coronary-artery calcium (CAC)
score. He exercised regularly and
was asymptomatic. There was no
family history of premature coro-
nary artery disease (CAD). He
was not overweight, had never
smoked, and did not have diabe-
tes. His blood pressure was 122/78
mm Hg. In 2006, he had under-
gone an electron-beam comput-
ed tomographic (CT) scan in re-
sponse to a newspaper ad. His
CAC score was 39. He underwent
a repeat scan in 2011 and had a
CAC score of 119. The radiologist
at the imaging facility told him
that he was “in danger of heart
attack and might not make it to
60.” His only medication was
rosuva­statin, which he had been
taking at a 5-mg dose daily for
3 years. His high-density lipopro-
tein (HDL) cholesterol level was
43 mg per deciliter, and his low-
density lipoprotein (LDL) choles-
terol level was 86 mg per deciliter.
More than half of Americans
will die of cardiovascular disease,
and many of those will have sud-
den cardiac death or acute myo-
cardial infarction as its first man-
ifestation. Therefore, the ability
to screen for early CAD is appeal-
ing from a preventive heath per-
spective. CAC scoring is a sensi-
tive and quantitative method of
detecting calcium in the coro-
nary arteries (see images). Because
CAC is almost always found with-
in atherosclerotic plaque, a posi-
tive CAC score directly identifies
the presence of CAD. Recent
studies of CAC scoring have fo-
cused primarily on risk stratifi-
cation. There is unanimous agree-
ment among the guidelines that
294
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Interpreting the Coronary-Artery Calcium Score
CAC scoring is not helpful in
screening patients at either very
low risk or high risk for CAD.
Guidelines vary on the question
of whether it’s indicated for
screening asymptomatic patients
at intermediate risk for CAD,
usually defined as those with a
Framingham risk score of 10 to
20% over 10 years (1 to 2% per
year). Screening of symptomatic
patients with known CAD is not
helpful. A recent study of 10,037
symptomatic patients undergoing
CT coronary angiography showed
that the absence of CAC did not
rule out the presence of obstruc-
tive CAD, nor did CAC scoring
add incremental prognostic infor-
mation to that provided by clini-
cal risk factors and the severity
of CAD.1
So far, there have been no pro-
spective randomized, controlled
trials demonstrating that an ab-
normal CAC score influences
treatment decisions or outcomes.
The limitations of applying CAC
scoring to screening broad popu-
lations are numerous and have
been extensively reviewed.2 Never-
theless, CAC scoring is offered to
the public by direct advertising.
Such ads typically suggest paying
with a flexible spending account,
health insurance, or cash. Physi-
cian referral is not needed. Pa-
tients who undergo self-referred
CAC scoring and have a positive
score are told to go to their phy-
sician for advice. How does a
physician interpret a CAC score
and counsel a patient such as the
one described above?
A number of obvious clinical
questions arise. Is a CAC score of
119 considered high? What is the
significance of the increase in
n engl j med 366;4  nejm.org  january 26, 2012
The New England Journal of Medicine
CAC score from 39 to 119 over a
5-year period? This patient was
told that he was in danger of a
heart attack and might not make
it to the age of 60. Was that true?
Did he need stress testing or cor-
onary angiography? The website
of the facility that performed his
scan states that “the higher the
calcium score, the greater the like-
lihood of a future coronary event
such as a heart attack or the
need for angioplasty, stents or by-
pass surgery.” The patient there-
fore believed that the areas of
CAC would require treatment with
stents or bypass surgery. Was
that true? If not, what therapy
should have been prescribed?
In considering these questions,
it’s important to evaluate the
CAC score within the clinical con-
text. As a rule, data from the
Multi-Ethnic Study of Atheroscle-
rosis (MESA) and other trials sug-
gest that a CAC score below 100
indicates low risk, and a score
above 300 indicates high risk.
The Framingham risk calculator
yields a 10-year risk of cardiac
death or myocardial infarction of
4.5% (<0.5% per year) in the pa-
tient described above. According
to the guidelines, CAC scoring was
not needed, because this man’s
predicted coronary event rate was
low. Nevertheless, recent evidence
from MESA indicates that CAC
scoring can significantly reclas-
sify risk.3 The MESA website con-
tains a useful tool that incorpo-
rates the CAC score as well as
clinical risk factors. According to
the MESA arterial age calculator
(www.mesa-nhlbi.org), this pa-
tient’s 10-year risk of death or
myocardial infarction would be
reclassified from 4.5% according
 PERSPECTIVE Interpreting the Coronary-Artery Calcium Score

A B absent,1 particularly in younger

patients who may have soft fatty
RCA
atheromas (see images).
Although the CAC score has
PA
not been shown to affect out-
LAD comes or change the appropriate
Ao therapy, it can be useful in en-
Soft plaque couraging medical compliance.
LCx in LAD
A recent randomized trial dem-
onstrated that subjects who un-
derwent CAC scoring before
counseling about risk-factor mod-
Multidetector CT Coronary Angiography in a Patient with an Abnormal Calcium Score ification had greater improve-
and Calcified Plaques (Panel A) and a Patient with Non–Flow-Limiting Atherosclerosis ments in systolic blood pressure,
without Calcification (Panel B). LDL cholesterol levels, and waist
In Panel A, calcified plaques (bright white areas) are seen in the left anterior descend- circumference than subjects who
ing (LAD) artery, the right coronary artery (RCA), and the left circumflex (LCx) coro-
did not undergo CAC scoring.5
nary artery. In Panel B, the arrows indicate the non–flow-limiting atherosclerosis in the
LAD coronary artery, without calcification; the CAC score is 0. Ao denotes aorta, and Thus, an abnormal CAC score
PA pulmonary artery. Images courtesy of Jeffrey M. Schussler, M.D. may motivate some patients to
take their prescribed medica-
to the Framingham scale to 10% tient. An abnormal CAC score in tions and follow recommended
with a CAC score of 39 and 12% an asymptomatic patient is not lifestyle changes.
with a CAC score of 119. Yet al- an indication for coronary angi- The patient described above
though the relative risk is more ography, nor are stents or bypass was very anxious about his ab-
than doubled, the absolute risk is surgery indicated to treat CAC. normal CAC score and the find-
roughly 1% per year, so the state- The abnormal CAC score should ing that it had increased between
ment that he was “in danger of a simply be viewed as documenta- 2006 and 2011. A stress echocar-
heart attack and may not make it tion of coronary atherosclerosis, diogram was ordered. He exercised
to 60” was misleading and unduly the appropriate treatment for for 13.5 minutes, in accordance
alarming. Although the change which is lifestyle modification, with the Bruce protocol, and had
in CAC score from 39 to 119 seems reduction of blood pressure and no symptoms, electrocardiograph-
to suggest progression of CAD, it LDL cholesterol levels, and anti- ic changes, or wall-motion ab-
only slightly increased this man’s platelet agents. Were the patient normalities. He was given die-
risk of myocardial infarction or to develop a clinical indication tary instruction and prescribed
death due to cardiac causes. Inter- for coronary revascularization, 325 mg of aspirin daily, and his
estingly, had this patient’s total such as an acute coronary syn- rosuvastatin dose was increased
cholesterol level been only 10 mg drome, the “culprit” lesion might to 20 mg daily. There are no plans
per deciliter higher, his MESA turn out to be a noncalcified to obtain a follow-up CAC score.
risk score would have increased plaque. In an intravascular ultra- Disclosure forms provided by the author
from 12% to 20% with a CAC sound study of the natural history are available with the full text of this arti-
cle at NEJM.org.
score of 119 — a disparity that of CAD, the plaque characteris-
highlights the need to consider tics most predictive of subsequent From the Department of Internal Medicine,
CAC scores only in the context of coronary events were plaque bur- Cardiology Division, Baylor University Med-
ical Center, Dallas.
other clinical risk factors, particu- den, thin fibrous cap, and small
larly cholesterol levels and blood luminal area (<4 mm2), not coro- 1. Villines TC, Hulten EA, Shaw LJ, et al.
pressure. nary calcium.4 Therefore, the areas Prevalence and severity of coronary artery
A stress test can be very help- of coronary calcium visualized by disease and adverse events among sympto-
matic patients with coronary artery calcifica-
ful in patients with abnormal CT are not necessarily the same tion scores of zero undergoing coronary
CAC scores to evaluate functional lesions that cause subsequent computed tomography angiography results
capacity and the presence or ab- coronary events. It should also from the CONFIRM (Coronary CT Angiogra-
phy Evaluation for Clinical Outcomes: an In-
sence of ischemia. It can also be remembered that a CAC score ternational Multicenter) registry. J Am Coll
help to reassure an anxious pa- of 0 does not mean that CAD is Cardiol 2011;58:2533-40.

n engl j med 366;4 nejm.org january 26, 2012 295

The New England Journal of Medicine
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Copyright © 2012 Massachusetts Medical Society. All rights reserved.
 PERSPE C T I V E
2. Bonow RO. Should coronary calcium
screening be used in cardiovascular preven-
tion strategies? N Engl J Med 2009;361:990-7.
3. Polonsky TS, McClelland RL, Jorgensen
NW, et al. Coronary artery calcium score and
risk classification for coronary heart disease
prediction. JAMA 2010;303:1610-6.
Selling Bone Marrow — Flynn v. Holder
I. Glenn Cohen, J.D.
O n December 1, 2011, in Flynn
v. Holder, the U.S. Court of
Appeals for the Ninth Circuit held
that the ban on selling “bone
marrow” that is part of the Na-
tional Organ Transplant Act
(NOTA) of 19841 does not encom-
pass “peripheral blood stem cells”
obtained through apheresis. This
ruling means that the sale of
blood stem cells for transplanta-
tion will now be permitted.2 The
court based its holding solely on
statutory interpretation of NOTA,
not the plaintiffs’ more radical
claim that the prohibition on
selling bone marrow violates the
Equal Protection Clause of the
U.S. Constitution, which prohibits
the federal and state governments
from denying any person the equal
protection of the law. For those
seeking to establish a constitu-
tional right to buy and sell body
parts in the United States, this
case was a loss, but for those
narrowly focused on blood stem
cells obtained through apheresis,
the decision legally sanctions a
commercial market.
In Flynn, NOTA was challenged
by a group of plaintiffs with vari-
ous interests, including parents
of children with leukemia and
aplastic anemia, which can be
fatal without bone marrow trans-
plantation; a parent of mixed-
race children, for whom sufficient-
ly matched donors are especially
scarce; and MoreMarrowDonors
.org, a California nonprofit cor-
296 n engl j med 366;4  nejm.org  january 26, 2012
The New England Journal of Medicine
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Copyright © 2012 Massachusetts Medical Society. All rights reserved.
Interpreting the Coronary-Artery Calcium Score
4. Stone GW, Maehara A, Lansky AJ, et al.
A prospective natural-history study of coro-
nary atherosclerosis. N Engl J Med 2011;364:
226-35.
5. Rozanski A, Gransar H, Shaw LJ, et al.
Impact of coronary artery calcium scanning
on coronary risk factors and downstream
poration that wanted to offer
$3,000 awards in the form of
scholarships, housing allowances,
or gifts to charities selected by
donors, initially to minority and
mixed-race donors of bone mar-
row cells.2
Before the district court, the
plaintiffs raised two primary argu-
ments.3 First, they argued that
the NOTA prohibition on selling
bone marrow violates the sub-
stantive due-process protections
of the Constitution, which pro-
tect a person’s power to possess
or do certain things despite the
desire of the government to the
contrary. Specifically, the plain-
tiffs argued that when a patient
needs an organ to survive and
someone is willing to sell it to
the patient, the Constitution pro-
hibits the state from interfering
with that exchange. The some-
what amorphous doctrine of sub-
stantive due process underlies
Supreme Court jurisprudence on
contraception and abortion, and
litigants have tried (unsuccessful-
ly) to use it to get courts to rec-
ognize a constitutional right to
assisted suicide. In Flynn, the dis-
trict court rejected this argument,
drawing an analogy between the
blood-stem-cell case and the D.C.
Circuit Court decision in Abigail
Alliance v. von Eschenbach, which
held that terminally ill patients
had no fundamental right to ob-
tain experimental drugs.3,4 This
aspect of the district court deci-
testing: the EISNER (Early Identification of
Subclinical Atherosclerosis by Noninvasive
Imaging Research) prospective randomized
trial. J Am Coll Cardiol 2011;57:1622-32.
Copyright © 2012 Massachusetts Medical Society.
sion was not challenged on ap-
peal, nor was it addressed by the
Ninth Circuit.2
Second, the plaintiffs argued
that as applied to bone marrow,
NOTA violates the Equal Protec-
tion Clause, because there is no
rational basis for allowing com-
pensation for providing blood,
sperm, and eggs while disallow-
ing compensation for providing
bone marrow. The Equal Protec-
tion Clause, which underlies much
of the Supreme Court jurispru-
dence on racial discrimination, re-
quires the state to articulate a
rational basis for distinctions that
it makes in the law (with a more
demanding inquiry if the distinc-
tions are based on race or sex).
Both the district court and the
Ninth Circuit rejected this chal-
lenge and found several possible
rational bases for the ban on sell-
ing bone marrow, including that
it is morally wrong to sell bone
marrow (just as it is wrong to
sell other body parts) because do-
ing so would turn human beings
into commodities; that poor peo-
ple would be coerced by financial
pressure into selling their organs;
that the rich would be at a sub-
stantial advantage in obtaining
organs; that donors would have a
strong incentive to provide an in-
accurate medical history; and that
although blood can legally be
sold, certain differences between
blood and bone marrow justify
the view of Congress that provid-