CAC Score 0 Unreliable to Rule Out Stenosis in Younger Patients

October 28, 2021

Cardiovascular risk assessment in symptomatic patients can rely heavily on insights that calcium scans add to the clinical evaluation, but their added value in ruling out obstructive coronary artery disease (CAD) might well depend on age, suggests an observational study of almost 24,000 such patients.

A minority of the cohort's 5043 patients with obstructive CAD, just over 14%, showed no sign of coronary calcium; that is, they had a coronary artery calcium (CAC) score of 0. But the prevalence of a zero CAC score was much higher in patients who were younger than 60 years.

In practice, patients showing no coronary calcium might be considered off the hook for further testing, including computed tomographic angiography (CTA). But "a strategy that uses a CAC score of 0 to rule out obstructive CAD in all symptomatic patients will likely miss a sizable proportion of younger patients" with obstructive CAD, contends a report published online October 27 in JAMA Cardiology.

To identify or rule out obstructive CAD in such cases, the report states, "an approach involving coronary CTA is needed despite a CAC score of 0."

"We found that obstructive CAD in younger patients, less than 60 years, with a CAC score of 0 was associated with higher relative risk than in patients without obstructive CAD," lead author Martin Bødtker Mortensen, MD, PhD, Aarhus University Hospital, Denmark, told | Medscape Cardiology.

Among patients younger than 60, the addition of obstructive CAD to a zero CAC score elevated the risk for death or a first myocardial infarction (MI) by a significant 80%. Obstructive CAD was defined conventionally as a coronary stenosis of at least 50% severity by CTA.

However, Mortensen said, "the overall event rate was still low in patients with a CAC score of 0, with a less-than 1% annual event rate irrespectively of whether there was obstructive CAD."

The analyses of a cohort of symptomatic patients taken from the Western Denmark Heart Registry "demonstrates the limitations of CAC as a diagnostic tool to identify or rule out obstructive CAD," even though a CAC score of 0 was still valuable for predicting risk, he said.

"Our results provide nuanced information for clinicians on the value of CAC as a gatekeeper for more advanced testing in patients with stable chest pain." A CAC score of 0 portends low risk for obstructive CAD regardless of age, but "it is important to realize that a large proportion of obstructive CAD in younger patients occur among those with a CAC score of 0," Mortensen observed.

"In both younger and older patients with high clinical suspicion, such as recurrent symptoms," he added, "physicians should understand the diagnostic limitations of a CAC-only approach to evaluate patients with stable chest pain."

The current study is important for "highlighting the potential limitations of CAC scoring to identify those who may benefit from statin therapy, particularly in younger adults," agrees an accompanying editorial by Sadiya S. Khan, MD, MSc, Northwestern University Feinberg School of Medicine, Chicago, and Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical School, Dallas.

Its findings "should be a reminder to physicians that the absence of CAC is not equivalent to the absence of atherosclerosis," and "should give pause to efforts to broaden the use of a CAC score of 0 to de-escalate or defer statin therapy in all individuals."

They caution, however, that all the study's patients had symptoms suggestive of CAD and were referred for coronary CTA, "and thus do not represent a primary-prevention, asymptomatic population, which is the focus of general screening."

In the total cohort of 23,759 symptomatic patients, in whom the median age was 58 (interquartile range, 49 - 65) and of whom 55% were women, the prevalence of obstructive CAD rose consistently by age decade, from a low of only 3% among patients younger than 40 to a high of 8% in those at least 70.

Also among the total cohort, 54% had a CAC score of 0. That was seen in 14% of the 5043 patients with obstructive CAD, but inconsistently by age.

Prevalence (%) of CAC Score 0, by Age, Among 5043 Symptomatic Patients With Obstructive CAD
Overall <40 y, n = 68 40–49 y, n = 562 50–59 y, n = 1486 60–69 y, n = 1963 ≥70 y, n = 964
14 58 34 18 9 5

The rate of first-time MI or death from any cause during the median 4.3-year follow-up (excluding the first 90 post-CTA days) per 1000 person-years was:

  • 4.31 among patients with CAC score 0

  • 4.07 among those with CAC score 0 and no CAD or only nonobstructive CAD

  • 7.11 among those with CAC score 0 and obstructive CAD

  • 15.00 for patients with CAC score greater than 0 and obstructive CAD

The current study "cautions against overinterpreting the clinical implications of a CAC score of 0," write Khan and Navar. "However, CAC scoring is still a useful tool for identifying those at highest risk for atherosclerotic CVD [cardiovascular disease]. Given the robust association between CAC and CVD, the presence of CAC in young adults should be a red flag for a high-risk patient."

HR* (95% CI) for First MI or Death, Obstructive CAD vs No Obstructive CAD, Among Patients with CAC Score of 0, by Age Group
Overall <60 y ≥60 y
1.51 (0.98–2.33) 1.80 (1.02–3.19) 1.24 (0.64–2.39)
*Adjusted for age, sex, smoking status, diabetes status, and symptom characteristics

This study was funded by Aarhus University Hospital. Mortensen had no disclosures. Statements on disclosures for the other authors are in the report. Khan reports receiving grants from the American Heart Association and the National Institutes of Health, and serving as web editor for JAMA Cardiology. Navar reports receiving grants from Bristol-Myers Squibb, Esperion, Amgen, and Janssen; personal fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, CSL, Esperion, Janssen, Lilly, Sanofi, Regeneron, Novo Nordisk, Novartis, The Medicines Company, New Amsterdam, Cerner, 89bio, and Pfizer; and serving as an associate editor for JAMA Cardiology.

JAMA Cardiol. Published online October 27, 2021. Abstract, Editorial

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