JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 66, NO. 15, 2015

2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER INC.

http://dx.doi.org/10.1016/j.jacc.2015.08.031

EDITORIAL COMMENT

Coronary Artery Calcium Scoring

Are We There Yet?*
Donald M. Lloyd-Jones, MD, SCM

or the past 2 decades, the consensus paradigm

likely to have events among the predicted high-risk

for prevention of atherosclerotic cardiovas-

groups. This is not surprising, because CAC repre-

cular disease (ASCVD) has been based on

sents the actual disease of interest and not merely the

the concept that the intensity of prevention efforts

presence of risk factors or risk markers for disease.

should match the absolute risk of the individual

But, to date, no national evidence-based guide-

patient. Application of this concept in international

lines have adopted a disease-screening approach;

guidelines has improved identication of those most

the current paradigm remains xed on risk-based

likely to benet from preventive therapies. The risk

screening.

scores upon which recommendations have been

based to date use data on traditional risk factors and

SEE PAGES 1643 AND 1657

risk markers to provide probabilities of disease and

In this issue of the Journal, McClelland et al. (4) use

guidance for instituting preventive therapies when

data from MESA (Multi-Ethnic Study of Atheroscle-

net clinical benet can be expected from doing so.

rosis) to develop novel risk equations for 10-year

This risk-based paradigm has been adopted broadly

prediction of coronary heart disease (CHD) that in-

for cholesterol guidelines (1,2) and recommendations

clude traditional risk factors and markers as well

regarding use of aspirin (3).

as the CAC score as covariates. As expected, they

During the same time period, advances in imaging

describe signicant improvements to the discrimina-

technology have allowed for accurate detection of

tion and calibration of the risk equations with the

subclinical atherosclerotic disease and important

addition of the CAC score. In addition, they assess the

surrogates, which add independent information and

utility of the new equations in 2 well-described and

improve accuracy for prediction of risk for future

similar external cohorts, the German HNR (Heinz-

events. These modalities, such as coronary artery

Nixdorf Recall) Study and the U.S.-based DHS (Dallas

calcium (CAC) screening, can identify individuals with

Heart Study), and demonstrate good to excellent

subclinical atherosclerosis who are at higher risk than

discrimination and calibration in these cohorts. The

expected and those with minimal or no evidence of

methods used by these MESA investigators are so-

atherosclerosis, who tend to be at very low risk even

phisticated and highly appropriate, and their overall

in the presence of risk factors. In fact, CAC screening

conclusions t well within the context of the partici-

does a very good job of discriminating those most

pants of these studies. It is understandable, but un-

likely to have events among low- and intermediate-

fortunate, that the authors chose only to predict CHD

risk subgroups and identifying those who are not

events, because this ignores substantial amounts of

preventable risk from atherosclerotic stroke events,
particularly in women and African Americans. The

*Editorials published in the Journal of the American College of Cardiology

authors suggest that these new risk equations could

reect the views of the authors and do not necessarily represent the

be used in clinical practice, if a CAC score has been

views of JACC or the American College of Cardiology.

obtained, to guide decision-making.

From the Department of Preventive Medicine and Division of Cardiology,

Department of Medicine, Northwestern University Feinberg School of
Medicine, Chicago, Illinois. Dr. Lloyd-Jones is a MESA investigator; and

However, before we can conclude that now we are

there with CAC screening, we must consider some

he has reported that he has no relationships relevant to the contents of

methodological issues and underlying assumptions

this paper to disclose.

and understand their potential consequences. Most

Lloyd-Jones

JACC VOL. 66, NO. 15, 2015

OCTOBER 13, 2015:16546

CAC Scoring: Are We There Yet?

importantly, we must remember how we use ab-

Furthermore, incorporation of the CAC score into

solute risk prediction equations in clinical practice.

clinical risk prediction equations implies universal

They are typically designed to predict the natural

screening (as happened in MESA and the other co-

history of disease in the absence of intervention.

horts). The lack of a randomized screening trial

MESA, although contemporary, is not a natural his-

demonstrating the efcacy, utility (including po-

tory cohort. By design, MESA participants underwent

tential adverse events), cost-effectiveness, and net

CAC scoring at the baseline examination and at least

clinical benet of CAC screening, particularly in

once more during follow-up. For all the right reasons,

intermediate-risk patients when there is uncertainty

the MESA investigators shared this CAC score infor-

regarding decisions, is a substantial barrier to wide-

mation with participants and encouraged them to

spread adoption. Without these data, current clinical

discuss it with their own physicians. As might be

practice guidelines cannot provide strong evidence-

expected in the current environment, knowledge of

based recommendations to guide practice.

this information has been associated with increased

Until such data are available, or a consensus is

usage of evidence-based preventive therapies in

reached regarding switching to disease-based scre-

MESA participants (5). The increased use of statins,

ening for ASCVD, there may be a better way to think

aspirin, and antihypertensive medications has been

about the use of CAC screening. Nasir et al. (7),

proportional to the reported CAC scores. Participants

also in this issue of the Journal, provide data from

with higher CAC scores, who are therefore at higher

MESA to inform this approach (although the same

risk and would have experienced more events, have

caveats about natural history apply). These in-

been signicantly more likely to initiate preventive

vestigators observed that one-half of MESA parti-

therapies after the baseline examination. It was re-

cipants were in the net clinical benet groups

cently reported that >80% of MESA participants have

identied by the 2013 American College of Cardiology/

received some sort of preventive therapy during

American Heart Association cholesterol guidelines

follow-up (6). It is certain that participation in MESA,

(most due to a 10-year predicted risk $7.5%) who

with its attendant CAC screening, has led to the pre-

therefore might receive statin therapy after a patient-

vention of many events that would otherwise have

clinician discussion. In this group, the 41% with a

occurred in these individuals, but it is difcult to

CAC score of 0 had a lower, but nonzero, event rate

quantify the magnitude of effect. True natural history

(w0.5%/year) compared with the group with any CAC

prediction has thus been lost. Similar issues likely

(1.2%/year).

apply to the HNR and DHS cohorts, whose members

The optimal approach at present appears to be a

were also informed of their CAC results. This does not

sequential screening approach, with quantitative risk

discount the immense value of the cohorts, but it

assessment followed by selective CAC screening,

does mean we must understand the observed event

rather than universal screening. The value of classi-

levels in context.

fying individuals into very-low and very-high pre-

That the CAC score remains an independent pre-

dicted risk groups on the basis of risk factors remains,

dictor of CHD events is, in part, a testament to the

and there appears to be little debate about instituting

potential effect of disease screening rather than risk

drug therapy in the highest-risk groups (except in

screening. One suspects that CAC would be an even

those with high competing risk for mortality) and

stronger predictor in a true natural history cohort.

avoiding it in almost all of the low-risk group (except

However, because the new MESA risk equations

perhaps in those with a strong family history or

would be used to predict absolute risk for CHD in

extreme risk factor levels). It is also clear that the

the natural history clinical environment, it is dif-

utility of screening will vary on the basis of predicted

cult to know how to translate these results to the

riskthe yield of nding a high CAC score is low in

point of care for more representative populations of

those at low predicted risk, and a CAC score of

patients. How can a patient and clinician use

0 is increasingly uncommon with higher predicted

these new equations in the context of a risk dis-

risks, as previously shown by Okwuosa et al. (8) and

cussion of natural history, when some of the MESA

conrmed by Nasir et al (7). In the broad middle,

participants received downstream therapy that pre-

perhaps from 5% to 20% 10-year ASCVD risk, there is

vented events? Which ones were they? Would that

room for the patient-clinician discussion espoused by

apply to this patient? Can we accurately classify risk

recent guidelines (1,2), which could well be informed

without knowing what therapies this patient will

by judicious use of CAC screening. Starting with a

take in the future? Although still valuable, the in-

quantitative risk-based assessment, the patient and

formation provided by these equations is somewhat

clinician rst calculate the 10-year risk. If, after dis-

garbled.

cussion, they are uncertain whether the individual

1655

1656

Lloyd-Jones

JACC VOL. 66, NO. 15, 2015

OCTOBER 13, 2015:16546

CAC Scoring: Are We There Yet?

patient is likely to benet from initiating a statin,

CAC scoring seems appropriate when the patient

obtaining a CAC score would be reasonable. Finding a

and clinician want more information to guide their

CAC score of 0 in someone otherwise thought to be in

decision.

a net benet group is a powerful reason to consider

withholding statin therapy. Likewise, the presence of

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

a high CAC score in an individual at only moderate

Donald M. Lloyd-Jones, Department of Preventive

predicted risk should be a powerful motivator to

Medicine, Division of Cardiology, Feinberg School of

initiate and adhere to statin therapy. A screening

Medicine, Northwestern University, 680 North Lake

trial to test this approach is needed. In the mean-

Shore Drive, Suite 1400, Chicago, Illinois 60611.

time, sequential screening with judicious use of

E-mail: dlj@northwestern.edu.

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KEY WORDS atherosclerosis, coronary disease,

epidemiology, risk prediction

and continuation of cardiovascular preventive

medications. Circ Cardiovasc Qual Outcomes 2010;
3:22835.