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A zero coronary artery calcium (CAC) score didn't necessarily mean zero obstructive coronary artery disease (CAD) in symptomatic patients, a Danish group found.

Among those with a CAC score of zero, 3% of adults younger than 40 had obstructive CAD compared with 8% of those 70 and older in the large Western Denmark Heart Registry of 23,759 symptomatic patients, reported Martin Bødtker Mortensen, MD, PhD, of Aarhus University Hospital in Denmark, and colleagues.

Among patients with obstructive CAD confirmed on coronary CT angiography, the prevalence of a zero CAC score fell with increasing age:

• 58% of people younger than 40
• 34% of those ages 40-49
• 18% of those ages 50-59
• 9% of those ages 60 to 69
• 5% of those 70 and older

The formation of early noncalcified atherosclerotic lesions in young people explains the CAC score's decreasing diagnostic value for flagging obstructive CAD in this group, the study authors noted in.

"This finding was observed in both men and women separately. However, throughout the age spectrum, a substantially higher proportion of women with obstructive CAD had a CAC score of 0 as compared with men," they wrote.

"Thus, 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 and women with obstructive CAD," they concluded.

CAC scans still remain useful given that the presence of calcification in young adults should be a red flag for a high-risk patient, maintained JAMA Cardiology editors Sadiya Khan, MD, MSc, of Northwestern University Feinberg School of Medicine in Chicago, and Ann Marie Navar, MD, PhD, of the University of Texas Southwestern Medical School in Dallas.

In an , the pair emphasized the prevention of cardiovascular disease (CVD), despite a finding of zero CAC.

"Although the optimal timing of treatment with statins in young adults remains unknown, statins should not always be deferred until CAC develops. Initiation of therapy after the emergence of CAC is unlikely to restore a person to an equivalent low-risk state," Khan and Navar wrote.

"Emphasizing true primary prevention of atherosclerosis before evidence of subclinical atherosclerosis emerges is of paramount importance to improve population-level cardiovascular health and to mitigate the growing burden of CVD morbidity and mortality," they continued.

The Western Denmark Heart Registry includes 23,759 consecutive real-world patients (median age 58, 55% women) who had symptoms suggestive of CAD and underwent CT angiography in 2008 to 2017. Of these patients, 54% had a CAC score of zero.

The prevalence of obstructive CAD was 6% -- exceeding the 5% ceiling estimated by European Society of Cardiology guidelines, Bødtker Mortensen and colleagues highlighted.

Obstructive CAD in the absence of CAC was associated with a greater risk of myocardial infarction and mortality over a median 4.3 years of follow-up. Nevertheless, the annual absolute risk stayed below 1%, "suggesting a favorable future outcome in patients without coronary calcification," the authors wrote.

They acknowledged that their observational study was subject to potential bias, and their findings were not inherently generalizable to other populations.

"Available data suggest that the burden of CAC may differ across racial and ethnic groups, with lower CAC scores observed in non-Hispanic Black adults who are at higher risk for CVD compared with non-Hispanic white adults," noted Khan and Navar.

The relatively short follow-up was another limitation of the study, they added.

"Despite a robust and growing body of evidence on CAC and its association with CVD events, considerable work is still needed to establish how to best incorporate CAC into the current paradigm of CVD prevention, particularly in younger adults," the editorialists wrote.

"In the meantime, the findings of this study ... should be a reminder to physicians that the absence of CAC is not equivalent to the absence of atherosclerosis, particularly in younger adults and women. When CAC scoring is used in these populations, clinicians should remind patients that a CAC score of 0 is not a guarantee against CVD," the pair concluded.

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