Circulation

EDITORIAL

Coronary Artery Calcium

If Measuring Once Is Good, Is Twice Better?

Article, see p 665 Amit Khera, MD, MSc

Philip Greenland, MD
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You’re always you, and that don’t change,

and you’re always changing, and there’s nothing you can do about it.
—Neil Gaiman, The Graveyard Book

A
therosclerosis is a dynamic process that is constantly changing and mor-
phing. Unchecked, this constant change can lead to advancement and
disruption, culminating in ischemic heart disease and myocardial infarc-
tion. However, this dynamic nature also offers opportunities to intervene with
preventive therapies to halt or reverse course before these adverse outcomes oc-
cur. These properties also offer the allure of quantifying change in atherosclerosis
to better pinpoint and personalize atherosclerotic cardiovascular disease (ASCVD)
risk estimates.
Several novel screening tests have been evaluated to improve ASCVD risk as-
sessment; of these tests, coronary artery calcium (CAC) scanning has emerged as
the top contender. High CAC scores are associated with a markedly increased risk
of coronary heart disease (CHD) (4- to 10-fold higher) independent of other risk
factors, and CAC has been shown to improve clinical reclassification of CHD and
ASCVD risk.1–3 In addition, those with no CAC have a relatively good prognosis
and may consider deferring preventive therapies such as statins.4 There has been
growing interest in exploring whether repeat CAC scanning, thereby evaluating
change in the CAC score, could enhance cardiovascular risk prediction. An early
study from 2004 suggested that change in CAC may be a meaningful and addi-
tive contribution to predicting an individual’s risk.5 However, only in the last sev-
eral years have population-based studies become available with paired scans and
adequate numbers of ASCVD events.6,7
Using MESA (Multi-Ethnic Study of Atherosclerosis), Budoff et al6 examined the
relationship of CAC progression to CHD outcomes in a cohort of 6778 subjects
with an interscan interval of 2.5 years. They demonstrated that CAC change of a
fairly large magnitude (>100 U/y) was associated with hard CHD independent of
CHD risk factors and baseline CAC score (hazard ratio, 1.3; 95% confidence inter-
val, 1.1–1.5). However, no data were provided regarding the incremental value of The opinions expressed in this article are
CAC progression to baseline CAC regarding metrics such as improvement in the not necessarily those of the editors or
of the American Heart Association.
C statistic of the model or net reclassification improvement. Also, CAC change
was only the fifth strongest risk marker for CHD, following after baseline CAC, Key Words: Editorials ◼ computerized
tomography ◼ primary prevention
male sex, systolic blood pressure, and total cholesterol. In a study by Radford et ◼ risk factors
al8 from the Cooper Center Longitudinal Study, a referred clinic population, CAC
© 2018 American Heart Association, Inc.
progression was similarly independently associated with ASCVD events. However,
the contribution of CAC change to the prediction of these events was again mod- http://circ.ahajournals.org

680 February 13, 2018 Circulation. 2018;137:680–683. DOI: 10.1161/CIRCULATIONAHA.117.031951

 Khera and Greenland Value of Coronary Artery Calcium Progression

est when compared with the information contained in the fence about treatment, and CAC scoring appears to
the baseline CAC score. be particularly informative for this group.10 The 10-year
In the current issue of Circulation, Lehmann et al7 CHD/ASCVD risk ranges from 3% to 6%,7 although

EDITORIAL
revisit this topic in the population-based Heinz Nixdorf there is a large spectrum of CAC scores and accom-
Recall study. They evaluated 3281 subjects with paired panying risk levels in this group. Whether repeat CAC
scans performed over a larger interscan interval, 5.1 scoring provides incremental risk information in this
years, and with 7.8 years of follow-up after the second subgroup was not explored by the study by Lehmann et
scan, resulting in 85 hard coronary, 161 hard cardio- al,7 but the totality of evidence suggests that any added
vascular, and 241 total cardiovascular events inclusive information will be modest. Lehmann et al7 also sug-
of revascularization. The unique contributions of this gested that those with a CAC score >400 on the sub-
article beyond the longer interscan and follow-up pe- sequent scan are at higher risk than those remaining
riods include the assessment of 10 different proposed <400, yet the hard ASCVD risks with either subsequent
algorithms to quantify CAC progression and the inclu- score range (<400 or ≥400) were comparable in men
sion of rigorous statistical metrics to interrogate the and are only appreciably different in women.
incremental value of CAC progression to outcome pre-
diction. Although various measures of CAC progression
were independently associated with outcomes, none of
CAC Score >100‒399
the 10 CAC progression algorithms demonstrated an In our view, those on the higher end of this spectrum (ie,
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improvement in the C statistic or net reclassification of >100) would achieve little benefit from repeat scanning
risk for hard CHD or hard ASCVD compared with mod- because their risk level would generally be >5% 10-year
els including risk factors and baseline CAC score. ASCVD risk, a threshold where statins are already an ap-
Taken together, these studies and other recent pub- propriate option.9 It is worth noting that in patients with
lications in this area are beginning to form a frame- prevalent CAC, change in CAC is "inevitable" and "pre-
work for how to conceptualize the potential utility and dictable", as demonstrated by the Heinz Nixdorf investi-
application of repeat CAC scanning in clinical practice. gators11 in a prior manuscript. Applying their predictive
Although no formal guidelines are available, we be- equation to the current study, the authors demonstrat-
lieve that in general, the majority of the predictive in- ed that 68% of subjects had expected CAC progres-
formation is obtained from the initial CAC scan, with sion, with 19% having rapid progression and only 13%
little benefit from a second scan. However, several nu- with slow progression. In our experience, patients often
ances and caveats to this statement are best described do not appreciate that some increase in CAC score over
through subsetting of patients by CAC score category. time is generally expected and sometimes erroneously
interpret this change as a failure of preventive inter-
ventions. Without evidence for significant incremental
HIGH BASELINE CAC SCORE (≥400) information of repeat CAC scanning in this group, the
potential for misinformation and radiation risks appear
Patients with a high baseline CAC score are at consid- to outweigh potential benefits.
erable CHD and ASCVD risk (≈10% to 15% 10-year
risk).2,7 The current American College of Cardiology/
American Heart Association 2013 Cholesterol Guide- CAC Score 1‒100
lines state that when the decision to initiate a statin In patients with CAC scores of 1 to 100 who elect to
remains unclear, a CAC score ≥300 may be used to defer statin therapy or other preventive interventions, a
inform decision making (ie, can be used to up-classify case could be made for reassessment of CAC in concert
risk).9 As such, most patients with high CAC scores with repeat global ASCVD risk assessment after an ap-
warrant statin therapy. In this group, the value of repeat propriate interval (ie, 5 years). Such a strategy should
scanning is negligible. High-intensity statin therapy is only be pursued after an informed discussion with the
already reasonable because most will have a 10-year patient and only if the results would change manage-
ASCVD risk >7.5%, and withdrawing or withholding ment. Patients with CAC in this range are often young-
therapy based on subsequent scan results would be er, meaning the modest incremental cancer risk of re-
misguided. Thus, repeat scanning in this group should peat CAC scanning is greater than in older individuals,
be avoided. which should be incorporated in this discussion. More
definitive data in this subgroup of patients are needed.

INTERMEDIATE CAC SCORE (>1–399)

From both a Bayesian and clinical decision-making per- CAC OF 0
spective, most tests are best applied to intermediate- With much data now available, the prognostic value of
risk patients. Here, patients and physicians may be on a CAC score of 0 has come into focus, and many such

Circulation. 2018;137:680–683. DOI: 10.1161/CIRCULATIONAHA.117.031951 February 13, 2018 681

 Khera and Greenland Value of Coronary Artery Calcium Progression

patients receive a revised risk estimate below the statin offer insightful and important information in relatively
treatment threshold.4 A particularly valuable observa- few people.
tion from the study by Lehmann et al7 is the excellent
EDITORIAL

prognosis in those with repeat CAC scores of 0 (ie, dou-

ble zero group). In contrast, those patients who convert ARTICLE INFORMATION
and develop CAC have a slightly worse prognosis (≈1.5- Correspondence
fold higher risk). Some studies have suggested that the Amit Khera, MD, MSc, Division of Cardiology, University of Texas Southwestern
warranty of a CAC score of 0 is ≈5 years in that the Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390–8830. E-mail amit.
[email protected]
probability of a significant change in CAC is low when
the scanning interval is less than this. It should be noted
that although those who develop CAC have a higher Affiliations
risk, their absolute 10-year ASCVD risk is still quite low Department of Internal Medicine, Division of Cardiology, University of Texas
Southwestern Medical Center, Dallas (A.K.). Department of Preventive Medi-
(<5%). However, these patients would have a higher cine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.).
lifetime risk of ASCVD,12 and they are likely on a differ-
ent long-term risk trajectory than those who remain at
0. Taking this lifetime view in perspective, a repeat scan Disclosures
usually would not be indicated unless there were sig- None.

nificant levels of traditional risk factors making the war-

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Circulation. 2018;137:680–683. DOI: 10.1161/CIRCULATIONAHA.117.031951 February 13, 2018 683

 Coronary Artery Calcium: If Measuring Once Is Good, Is Twice Better?
Amit Khera and Philip Greenland

Circulation. 2018;137:680-683
doi: 10.1161/CIRCULATIONAHA.117.031951
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