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Multicenter Study
. 2022 Jan 1;7(1):36-44.
doi: 10.1001/jamacardio.2021.4406.

Association of Age With the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Coronary Stenosis in Symptomatic Patients

Martin Bødtker Mortensen  1   2 , Sara Gaur  1 , Attila Frimmer  1 , Hans Erik Bøtker  1 , Henrik Toft Sørensen  3 , Kristian Hay Kragholm  4 , Sand Rønnow Niels Peter  5 , Flemming Hald Steffensen  6 , Rebekka Vibjerg Jensen  1 , Michael Mæng  1 , Helle Kanstrup  1 , Michael J Blaha  2 , Leslee J Shaw  7 , Omar Dzaye  2 , Jonathon Leipsic  8 , Bjarne Linde Nørgaard  1 , Jesper Møller Jensen  1
Affiliations
Multicenter Study

Association of Age With the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Coronary Stenosis in Symptomatic Patients

Martin Bødtker Mortensen et al. JAMA Cardiol. .

Abstract

Importance: The diagnostic value is unclear 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.

Objective: 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.

Design, setting, and participants: This cohort study obtained data from the Western Denmark Heart Registry and had a median follow-up time of 4.3 years. Included patients were aged 18 years or older who underwent computed tomography angiography (CTA) between January 1, 2008, and December 31, 2017, because of symptoms that were suggestive of CAD. Data analysis was performed from April 5 to July 7, 2021.

Exposures: Obstructive CAD, which was defined as 50% or more luminal stenosis.

Main outcomes and measures: Proportion of individuals with obstructive CAD who had a CAC score of 0. 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. Risk factors associated with myocardial infarction and death were estimated.

Results: A total of 23 759 symptomatic patients, of whom 12 771 (54%) had a CAC score of 0, were included. This cohort had a median (IQR) age of 58 (49-65) years and was primarily composed of women (13 160 [55%]). Overall, the prevalence of obstructive CAD was relatively low across all age groups, ranging from 3% (39 of 1278 patients) in those who were younger than 40 years to 8% (52 of 619) among those who were 70 years or older. In patients with obstructive CAD, 14% (725 of 5043) had a CAC score of 0, and the prevalence varied across age groups from 58% (39 of 68) among those who were younger than 40 years, 34% (192 of 562) among those aged 40 to 49 years, 18% (268 of 1486) among those aged 50 to 59 years, 9% (174 of 1963) among those aged 60 to 69 years, to 5% (52 of 964) among those who were 70 years or older. The added diagnostic value of a CAC score of 0 decreased at a younger age, with a risk factor-adjusted diagnostic likelihood ratio of a CAC score of 0 ranging from 0.68 (approximately 32% lower likelihood of obstructive CAD than expected) in those who were younger than 40 years to 0.18 (approximately 82% lower likelihood than expected) in those who were 70 years or older. The presence of obstructive vs nonobstructive CAD among those with a CAC score of 0 was associated with a multivariable adjusted hazard ratio of 1.51 (95% CI, 0.98-2.33) for myocardial infarction and all-cause death; however, this hazard ratio varied from 1.80 (95% CI, 1.02-3.19) in those who were younger than 60 years to 1.24 (95% CI, 0.64-2.39) in those who were 60 years or older.

Conclusions and relevance: This cohort study found that the diagnostic value of a CAC score of 0 to rule out obstructive CAD beyond clinical variables was dependent on age, with the added diagnostic value being smaller for younger patients. In symptomatic patients who were younger than 60 years, a sizable proportion of obstructive CAD occurred among those without CAC and was associated with an increased risk of myocardial infarction and all-cause death.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kragholm reported receiving personal fees from Novartis outside the submitted work. Dr Mæng reported receiving personal fees from Novo Nordisk outside the submitted work. Dr Blaha reported receiving grants from the National Institutes of Health, US Food and Drug Administration, American Heart Association, Aetna Foundation, Amgen Foundation, and Novo Nordisk; and personal fees from Sanofi, Regeneron, Novartis, Bayer, Akcea, 89Bio, Kaleido, Inozyme, Kowa, Roche, and VoxelCloud outside the submitted work. Dr Leipsic reported serving as a consultant to and holding stock options in Circle CVI and HeartFlow; speaking fees from Philips; and an institutional grant from GE Healthcare. Dr Nørgaard reported receiving grants from HeartFlow outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Coronary Artery Calcium (CAC) and Obstructive Coronary Artery Disease (CAD)
A, Prevalence of obstructive CAD among patients with CAC score of 0. B, Prevalence of CAC score of 0 among patients with obstructive CAD.
Figure 2.
Figure 2.. Examples of the Likelihood of Obstructive Coronary Artery Disease (CAD) Across Different Age Groups and Risk Factor Burdens With and Without Information on a Coronary Artery Calcium (CAC) Score of 0
CAC score of 0 was associated with lower likelihood of obstructive CAD across all age groups and risk factor burdens in both men and women. The absolute decrease in the likelihood of obstructive CAD in the presence of CAC score of 0 was larger in older adults than younger patients and was more pronounced in men than women.
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