Absence of coronary calcification not equivalent to absence of atherosclerosis in young adults: JAMA

The diagnostic value is not clear of a 0 coronary artery calcium (CAC) score to rule out obstructive coronary artery disease (CAD) and near-term clinical events across different age groups. In the current issue of JAMA Cardiology, Mortensen et al have shown that a sizable proportion of obstructive CAD can occur among young patients without CAC while more than 90% patients (with symptomatic CAD) in the elderly age group had a score more than zero. Thus the decision to defer statin therapy in young subjects for primary prevention should not be based solely on CAC scores.

Based on the available evidence of the role of CAC in improving the estimation of CVD risk, multisociety practice guidelines from the United States, Europe, and others endorse the selective use of CAC in adults aged 40 to 75 years with borderline or intermediate estimated 10-year atherosclerotic CVD risk to guide the intensification of preventive strategies (eg, lipid-lowering therapy).

When CAC is absent, current American Heart Association/American College of Cardiology guidelines recommend that clinicians consider providing no statin to some patients who are not at an elevated risk on the basis of smoking status, family history, and diabetes.

To assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD and to assess the implications of such a CAC score and obstructive CAD across different age groups, Mortensen et al obtained data from the Western Denmark Heart Registry with median follow-up time of 4.3 years.

The study included patients were aged 18 years or older who underwent computed tomography angiography (CTA) because of symptoms that were suggestive of CAD. Obstructive CAD was defined as 50% or more luminal stenosis. Risk-adjusted diagnostic likelihood ratios were used to assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD beyond clinical variables.

The study provided following results:

1. Among 23 759 patients 54% had a CAC score of 0 and 21% had obstructive CAD.

2. Among those with evidence of obstructive CAD, 14% had a 0 CAC score.

3. When stratified by age, younger adults with obstructive disease were far less likely than older adults to have any CAC; 58% of patients aged 18 to 39 years with obstructive disease had 0 CAC score compared with only 5% of patients who were 70 years or older with obstructive disease.

4. Women with obstructive disease were also less likely to have any CAC, suggesting that CAC scoring may perform worse as a strategy to identify younger adults and women who may not benefit from statins.

5. Although the proportion of the overall cohort with a CAC score of 0 was low (14%), their overall burden of disease was high.

6. At a median follow-up of 4.3 years, nearly one-third of events occurred in those with a CAC score of 0.

"These findings are not surprising given what is known about the biological processes involved in atherosclerosis. The processes leading to CAC begin early in life and take decades to progress from early atherosclerotic lesions to calcified plaques. Thus, many adults, particularly earlier in life, who will subsequently develop clinically significant atherosclerosis may have noncalcified lesions but a CAC score of 0", write Khan et al in an accompanying editorial.

The analysis by Mortensen et al is an important addition to the literature, highlighting the potential limitations of CAC scoring to identify those who may benefit from statin therapy, particularly in younger adults. 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 goal of primary prevention should be to prevent the atherosclerotic lesions that lead to CAC, not to wait for CAC to develop before initiating risk-lowering therapy", conclude Khan et al.

Source: JAMA Cardiology:

1. doi:10.1001/jamacardio.2021.4406

2. doi:10.1001/jamacardio.2021.4413