By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: Using coronary CT strategy as a diagnostic first line in patients with symptoms suggestive of coronary artery obstruction revealed relying on the coronary calcium score alone is inadequate for younger patients with a higher frequency of non-calcified obstructions.
SOURCE: Mortensen MB, Gaur S, Frimmer A, et al. Association of age with the diagnostic value of coronary artery calcium score for ruling out coronary stenosis in symptomatic patients. JAMA Cardiol 2021; Oct 27. doi: 10.1001/jamacardio.2021.4406. [Online ahead of print].
Although a coronary artery calcium (CAC) score of 0 is associated with a low likelihood of obstructive coronary artery disease (CAD), that does not mean risk is nonexistent. Since early coronary plaques may not be calcified, the relationship between CAC and obstructive disease may be age-related. Investigators from the Western Denmark Heart Registry used data about consecutive real-world patients who exhibited symptoms suggestive of CAD and underwent coronary calcium scoring followed by CT angiography (CTA) to test this association.
In Western Denmark, CTA is a first-line diagnostic test for non-emergency patients with suspected obstructive CAD. For this analysis, Mortensen et al included all patients older than age 18 years who underwent CTA between 2008 and 2017. Only patients with inconclusive test results, missing results, or a history of known CAD were excluded. The authors obtained clinical data from the Danish National Patient Registry. They categorized the severity of CAD as none (0% luminal stenosis and Agatston score of 0), nonobstructive (1% to 49% stenosis), or obstructive (> 49%). The primary endpoint was myocardial infarction and all-cause death. All analyses were corrected either for age and sex or age, sex, smoking, diabetes, and symptom characteristics.
Among the study cohort of 23,759 patients (45% men, mean age = 58 years), 54% recorded a CAC score of 0. The prevalence of obstructive CAD in patients with a CAC score of 0 in the overall population was 6%. In those younger than age 40 years, it was 3%; age 40-49 years, it was 5%; age 50-59 years, it was 6%; age 60-69 years, it was 6%; and older than age 70 years, it was 8%. Overall, 14% of patients with obstructive CAD recorded a CAC score of 0; percentages declined with age: 58% in those younger than age 40 years, 34% in those age 40-49 years, 18% in those age 50-59 years, 9% in those age 60-69 years, and 5% in those age 70 years or older. Although the distribution by age was similar, overall, women with obstructive CAD more often recorded a CAC of 0.
The overall diagnostic value of a CAC score of 0 for excluding obstructive CAD was a 63% lower likelihood than expected based on other clinical characteristics. However, this varied across different age groups, ranging from 32% in those younger than age 40 years to 82% in those age 70 years and older. This effect was more pronounced in women younger than age 40 years (18% vs. 41% in men younger than age 40 years). During the mean follow-up of four years, the primary outcome occurred in 31% of patients with a CAC score of 0, with an adjusted multivariable hazard ratio (HR) of 1.51 (95% CI, 0.98-2.33). The HR varied with age, from 1.80 in those younger than age 60 years to 1.24 in those older than age 60 years. The authors concluded the diagnostic value of a CAC score of 0 varied with age. There was less value in younger patients with symptoms suggestive of obstructive CAD. Those younger than age 60 years with a CAC score of 0 made up a large proportion of those experiencing the primary endpoint.
Because of the logistical issues surrounding stress testing, many chest pain units have moved to using CTA to diagnose obstructive CAD. However, when coronary calcium is present, CTA becomes less accurate for detecting stenoses. Thus, CTA often is preferentially directed at younger patients who are less likely to exhibit significant calcium. In fact, many younger patients will show no detectable coronary calcium. The risk of obstructive CAD in such patients is low, but it is not zero.
Mortensen et al hypothesized the diagnostic value of the CAC score would be age-related, based on the pathophysiology of atherosclerosis wherein calcium deposition is a later manifestation of coronary plaques. In this study, a CAC score of 0 was more common in younger patients, especially women (55%). The prevalence of obstructive CAD in those with a CAC score of 0 was low, ranging from 3% in those younger than age 40 years to 8% in those older than age 70 years. However, in those with obstructive CAD, 14% overall recorded a CAC score of 0; the proportion was higher in younger patients (58% in those younger than age 40 years vs. 5% in those older than age 70 years). Consequently, the diagnostic value of a CAC score of 0 was less in younger patients and women. Although the overall risk of the combined primary outcome of myocardial infarction or all-cause mortality was low in patients with a CAC score of 0 (< 1%), one out of three events occurred in patients with a CAC score of 0. Thus, CTA is necessary in younger patients with symptoms suggestive of CAD, since relying on the CAC score alone is problematic.
There were weaknesses here. A referral bias to CT scan cannot be excluded, but this was the recommended approach. This was a relatively low-risk population (less than 1% experienced the primary outcome). More importantly, the authors observed changes in management based on the CT scans, but those changes were not considered in the analyses. Also, researchers did not consider the severity of calcium deposition. Nevertheless, this was a large, real-world study, with baseline characteristics representative of everyday practice patients.