Coronary artery calcium identified on non-gated chest computed tomography guides downstream coronary computed tomography angiography
Introduction
Coronary artery calcium (CAC) is one of the most common incidental findings on non-gated chest computed tomography (CT) in patients imaged for noncardiac indications (1). Some studies have reported that a CAC assessment with non-gated chest CT is reliable and has good agreement with Agatston scores from electrocardiograph (ECG)-gated CT (2-4). Moreover, the existence and extent of CAC on non-gated chest CT are directly correlated with the risk of cardiovascular diseases (5-7).
Coronary computed tomography angiography (CTA) is a safe non-invasive modality that serves as an accurate gatekeeper for invasive coronary angiography (ICA) in stable chest pain and suspected coronary artery disease (CAD) patients (8,9). However, the diagnostic accuracy of coronary CTA is still constrained by spatial resolution (10). Additionally, the predictive value of coronary CTA is largely dependent on the disease prevalence in the study population (11). A previous study found that when the CAC score measured by ECG-gated CT was ≥600, the diagnostic performance of coronary CTA for obstructive CAD deteriorated significantly, and suggested that the CAC score should be considered before using coronary CTA to rule out obstructive CAD (12). However, the relationship between the extent of CAC on non-gated chest CT and the diagnostic accuracy of coronary CTA has not yet been studied.
Therefore, the aim of this study was to assess the impact of CAC identified on non-gated chest CT on the accuracy of coronary CTA in diagnosing obstructive CAD. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-291/rc).
Methods
Population
Patients who underwent coronary CTA for suspected CAD from September 2021 to September 2022 at our hospital and had concurrent non-gated chest CT images and ICA were retrospectively recruited. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Beijing Friendship Hospital ethics committee (approval No. 2024-P2-380-01). The requirement for individual consent for this retrospective analysis was waived.
The patient inclusion criteria included the following: (I) underwent coronary CTA examination; (II) underwent non-gated chest CT within 1 year of coronary CTA examination; and (III) ICA testing had been performed within 1 year of coronary CTA examination. The exclusion criteria were as follows: (I) patients underwent previous coronary stent implantation, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty before coronary CTA or non-gate chest CT; and (II) the degree of coronary artery stenosis could not be assessed on coronary CTA.
Clinical data collection
We collected clinical data regarding gender, age, and chest discomfort symptoms, and evaluated the pre-test probability (PTP) of participants based on the PTP model recommended by the 2019 European Society of Cardiology Guidelines (9).
Non-gated chest CT image analysis for CAC grading
A semi-quantitative score of CAC was used to assess a CAC score for each major coronary artery (the left main trunk, left anterior descending artery, left circumflex artery, right coronary artery) proposed by Shemesh et al. (13): 0, no CAC; 1, when less than one-third of the length of the entire artery showed calcification; 2, when one-third to two-thirds of the artery showed calcification; 3, when more than two-thirds of the artery showed calcification. The total CAC score (range, 0–12) as the sum of the score of each major coronary artery was used for CAC severity categorization, and the four categories of CAC were as follows: absent [0], mild [1–3], moderate [4–6], and severe [7–12].
The semi-quantitative CAC assessments were performed by a radiologist with four years of imaging experience. For inter-observer agreement analysis, a subset of 20 cases was independently evaluated by an additional reader with three years of experience, and agreement between the two readers was assessed.
Coronary stenosis assessment with coronary CTA
Coronary stenosis with a diameter of ≥ 2 mm was visually graded into the following categories: no stenosis, 1–24% mild stenosis, 25–49% mild stenosis, 50–69% moderate stenosis, 70–99% severe stenosis, and complete occlusion. Coronary CTA results were obtained from radiology reports. Every radiology report was performed by 2 readers (radiology residents, with 1–3 years of radiology experience; and radiologists, with ≥5 years of radiology experience). Coronary CTA results were classified as either obstructive CAD-negative or obstructive CAD-positive based on whether the degree of luminal stenosis identified by coronary CTA was ≥50% (14).
Data acquisition and analysis of ICA
ICA results were derived from clinical medical records. ICA was the gold standard for the degree of coronary artery stenosis, and obstructive CAD was diagnosed in patients with ≥50% coronary artery stenosis on ICA.
Statistical analysis
The software SPSS 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Measurement data conforming to normal distribution were expressed as mean ± standard deviation; the measurement data of the non-normal distribution were expressed as the median (interquartile range) [M (P25, P75)]. Confidence intervals (CI) were calculated using percentile method. The difference of obstructive CAD distribution in groups with different CAC levels was analyzed using chi-square test. The diagnostic accuracy of coronary CTA was calculated for population and different CAC degree groups, using area under the receiver operating characteristic (ROC) curve (AUC) and presenting 95% confidence interval (CI). By comparing AUC, the difference of diagnostic accuracy of coronary CTA in groups with different CAC levels was analyzed. The inter-reader agreement for the assignment of CAC was determined with Cohen’s kappa coefficient. All P values were bilateral and 95% CI were also present, and P<0.05 was considered statistically significant for the difference examined.
Results
Baseline data
A total of 337 patients were included in this study. In 482 patients who had coronary CTA with chest CT and coronary angiography within one year, 145 were excluded because of a history of coronary surgery or insufficient image quality (Figure 1). The demographic and clinical characteristics of the participants are shown in Table 1. The average age was 64 and 61% were male. The numbers of individuals with absent, mild, moderate, and severe CAC (semi-quantitative CAC scores was 0, 1–3, 4–6, and 7–12) on non-gated chest CT were 33 (9.8%), 82 (24.3%), 103 (30.6%), and 119 (35.3%), respectively. In this study, approximately 80% of the participants underwent coronary CTA examination because of chest discomfort symptoms. Among them, the majority of the pre-test probabilities were moderate or low risk. The other 20% of the participants were hospitalized for other reasons or underwent a physical examination.
Table 1
| Characteristics | Value (n=337) |
|---|---|
| Age, years | 64 [57–70] |
| Men | 207 (61.4) |
| Obstructive CAD | 281 (83.4) |
| Asymptomatic individuals | 66 (19.6) |
| Symptomatic individuals | 271 (80.4) |
| Chest pain type | |
| Typical | 40 (14.8) |
| Atypical | 66 (24.4) |
| Non-anginal | 35 (12.9) |
| Dyspnea | 130 (48.0) |
| Pre-test risk | |
| Very low | 11 (4.1) |
| Low | 102 (37.6) |
| Intermediate | 154 (56.8) |
| High | 4 (1.5) |
| Very high | 0 |
| CAC semi-quantitative score | |
| 0 | 33 (9.8) |
| 1–3 | 82 (24.3) |
| 4–6 | 103 (30.6) |
| 7–12 | 119 (35.3) |
Values are median [interquartile range] or n (%). CAC, coronary artery calcium; CAD, coronary artery disease.
Subgroup analysis
Among the cases with semi-quantitative CAC scores on non-gated chest CT being 0, 1–3, 4–6, and 7–12, the proportions of obstructive CAD were 75.8%, 73.2%, 81.6%, and 94.1%, respectively (Table 2). The proportion of obstructive CAD in the group without CAC was lower than that in the group with CAC; however, the difference was not statistically significant (P=0.775). According to the chi-square test, the proportion of obstructive CAD in the group with severe CAC (semi-quantitative CAC score ≥7) was different from the other three subgroups, and the difference was statistically significant (P=0.004) (Table 3).
Table 2
| CAC subgroup | Obstructive CAD | All, n | Positive rate | |
|---|---|---|---|---|
| Positive, n | Negative, n | |||
| All participants | 281 | 56 | 337 | 83.4% |
| CAC score =0 | 25 | 8 | 33 | 75.8% |
| CAC score =1–3 | 60 | 22 | 82 | 73.2% |
| CAC score =4–6 | 84 | 19 | 103 | 81.6% |
| CAC score =7–12 | 112 | 7 | 119 | 94.1% |
CAC, coronary artery calcium; CAD, coronary artery disease.
Table 3
| CAC subgroup | Pearson χ2 | P value | α reference value |
|---|---|---|---|
| All | 17.702 | 0.0005 | 0.05 |
| Pairwise comparisons | |||
| 0 vs. 1–3 | 0.082 | 0.775 | 0.0083 |
| 1–3 vs. 4–6 | 1.86 | 0.173 | 0.0083 |
| 4–6 vs. 7–12 | 8.429 | 0.004 | 0.0083 |
CAC, coronary artery calcium; CAD, coronary artery disease.
Diagnostic performance evaluation of coronary CTA
The AUC of coronary CTA in overall cases was 0.609 (0.520, 0.698). The AUC of coronary CTA in four subgroups with absent, mild, moderate, and severe CAC (semi-quantitative CAC scores of 0, 1–3, 4–6, and 7–12) on non-gated chest CT was 0.650 (0.417, 0.883), 0.665 (0.518, 0.812), 0.549 (0.399, 0.700), and 0.491 (0.273, 0.709), respectively (Table 4, Figure 2). The AUC of coronary CTA in the moderate and severe CAC groups was lower than that in the absent and mild CAC groups. In the moderate CAC group, the AUC of coronary CTA was close to 0.5, which implies a very low diagnostic accuracy. In the severe CAC group, the AUC of coronary CTA was lower than 0.5, indicating no diagnostic value (Figure 3). In the same way, the negative predictive values (NPV) in the moderate and severe CAC groups were lower than those in the absent and mild CAC groups (CAC =4–6, CAC =7–12 vs. CAC =0, CAC =1–3: 0.38, 0 vs. 0.44, 0.80). Notably, the NPV in severe CAC group decreased to 0.
Table 4
| CAC | n | SEN | SPE | PPV | NPV | AUC (95% CI) |
|---|---|---|---|---|---|---|
| All | 337 | 95.02% | 26.79% | 86.69% | 51.72% | 0.609 (0.520, 0.698) |
| CAC subgroups | ||||||
| 0 | 33 | 80.00% | 50.00% | 83.33% | 44.44% | 0.650 (0.417, 0.883) |
| 1–3 | 82 | 96.67% | 36.36% | 80.56% | 80.00% | 0.665 (0.518, 0.812) |
| 4–6 | 103 | 94.05% | 15.79% | 83.16% | 37.50% | 0.549 (0.399, 0.700) |
| 7–12 | 119 | 98.21% | 0.00% | 94.02% | 0.00% | 0.491 (0.273, 0.709) |
| CAC cutoff =4 | ||||||
| <4 | 115 | 91.76% | 40.00% | 81.25% | 63.16% | 0.659 (0.535, 0.783) |
| ≥4 | 222 | 96.43% | 11.54% | 89.15% | 30.00% | 0.540 (0.416, 0.664) |
| CAC cutoff =7 | ||||||
| <7 | 218 | 92.90% | 30.61% | 82.20% | 55.56% | 0.618 (0.521, 0.714) |
| ≥7 | 119 | 98.21% | 0.00% | 94.02% | 0.00% | 0.491 (0.273, 0.709) |
AUC, area under the curve; CAC, coronary artery calcium; CI, confidence interval; CTA, computed tomography angiography; NPV, negative predicate value; PPV, positive predicate value; SEN, sensitivity; SPE, specificity.
Using the semi-quantitative CAC scores of 4 and 7 on non-gated chest CT as the threshold values, patients were respectively divided into two groups (Table 4, Figure 2). Among the cases with a semi-quantitative CAC score <4 on non-gated chest CT, the AUC of coronary CTA was 0.66. Among the cases with a semi-quantitative CAC score ≥4, the AUC of coronary CTA was lower, at 0.540. Among the cases with CAC <7, the AUC was 0.618. Among the cases with CAC ≥7, the AUC was 0.49, indicating that coronary CTA has no diagnostic value in this subgroup. In the groups with a semi-quantitative CAC score <4 and a semi-quantitative CAC score ≥4, the NPV of coronary CTA was 0.59 and 0.30, respectively. In the groups with a semi-quantitative CAC score <7 on chest CT and semi-quantitative CAC score ≥7, the NPV of coronary CTA was 0.52 and 0, respectively.
Inter-reader agreement
The inter-observer agreement for the semi-quantitative CAC score categories was substantial, with a kappa value of 0.71 (P<0.001).
Discussion
This study found that the AUC of coronary CTA in patients with moderate and severe CAC on non-gated chest CT was lower than the overall AUC. In the subgroup of patients with severe CAC on non-gated chest CT (semiquantitative score ≥7), the AUC of coronary CTA was lower than 0.5, indicating no diagnostic value, and the NPV was 0. In the subgroup of patients with severe CAC on non-gated chest CT (semiquantitative score ≥7), the proportion of obstructive CAD was significantly higher than that of the other three groups.
Previous studies have suggested that CAC is an important factor affecting the diagnostic value of coronary CTA (12). Firstly, the presence of CAC can introduce artifacts in coronary CTA images. When the degree of CAC is heavy, the overall coronary CTA image quality decreases. Moreover, due to the low spatial resolution of CTA, extensive coronary calcification is a major source of uncertainty when diagnosing coronary lumen stenosis using coronary CTA (10). CAC can visually enlarge the volume of a single plaque, which tends to exaggerate the degree of lumen narrowing in a single lesion, resulting in a reduced AUC. Previous studies have demonstrated that the severity of calcification affects the consistency of coronary CTA and ICA in determining obstructive lesions at the level of a single coronary artery segment (15). In our study, the degree of the most severe coronary artery stenosis was evaluated. Our study found that when the semi-quantitative CAC score was ≥4, the diagnostic efficacy of coronary CTA began to decline. Especially when CAC =7–12, the diagnostic efficiency of coronary CTA in this subgroup was significantly reduced, the AUC of coronary CTA was even lower than 0.5. The positive likelihood ratio with semi-quantitative CAC score ≥4 was significantly lower than those in the two groups with CAC <4, and the false positive rate of coronary CTA increased with the increase of CAC degree.
In addition, the predictive value of coronary CTA is largely dependent on the disease prevalence in the study population (11). Previous studies and guidelines have asserted that coronary CTA served as a gatekeeper for ICA in patients at low to moderate pre-test risk (8). Most of the cases in our study were of low-to-moderate pre-test risk. However, we found that when the semi-quantitative CAC score was 7–12, the obstructive CAD proportion was higher than it was in the other subgroups, and the difference was statistically significant. Several studies have demonstrated that CAC is an independent predictor of obstructive CAD—people with high CAC have a higher probability of developing obstructive CAD (16-18). Some guidelines have recommended using CAC as an assessment factor for increased or decreased risk of PTP (9,19). Guidelines recommend that coronary CTA be used primarily to exclude patients with obstructive CAD, so NPV is an important indicator of the diagnostic efficacy of coronary CTA (9). However, the NPV of the examination method decreased with the increase of population prevalence. In our study, when the semi-quantitative CAC score was ≥4, the NPV of coronary CTA was lower than that when the semi-quantitative CAC score was <4; in particular, when the semi-quantitative CAC score was 7–12, the NPV was 0. Thus, in patients with a semi-quantitative CAC score ≥7, coronary CTA has limited diagnostic value for excluding obstructive CAD.
The findings from this study are similar to those of previous studies on the diagnostic value of coronary CTA guided by gated CT assessment for CAC scores: when CAC is severe, coronary CTA results may be unreliable (12). Previous studies have suggested that CAC combined with coronary CTA can provide incremental predictive value for the accuracy of diagnosing obstructive CAD (20). For non-diagnostic results on coronary CTA, the degree of CAC can help better judge whether they are inclined to obstructive CAD, thus improving the diagnostic efficiency of obstructive CAD.
However, the ECG-gated cardiac CT-CAC evaluation requires additional electrocardiogated scans or is performed in conjunction with coronary CTA. Recently, many studies have found that CAC can also be detected and quantified on routine or low-dose non-gated chest CT for non-cardiac reasons (21,22). The CAC identified on non-gated chest CT dose not require additional electrocardiogated scans, constituting a highly potential screening tool. In our study, when the CAC semi-quantitative score was ≥7, the diagnostic efficacy of coronary CTA was found to be almost negligible in this subgroup, particularly the ability to exclude obstructive CAD was reduced. Thus, we suggested that for patients with a semi-quantitative CAC score of ≥7 on chest CT, coronary CTA is less effective in providing accurate stenosis assessment and coronary angiography should be considered if luminal severity will change patient management. In addition to considering the appropriate downstream diagnostic strategies, appropriate medical management should be initiated irrespective of luminal stenosis severity.
Our study also has some limitationsŁşFirstly, although semi-quantitative CAC categories on chest CT demonstrate excellent agreement with Agatston score-based risk stratification, subtle discrepancies in risk classification thresholds exist across studies, likely attributable to the inferior objectivity and reproducibility of the visual scoring method (23,24). Consequently, the specific cut-off of a semi-quantitative CAC score ≥7 necessitates further validation. In contrast, the Agatston score, as an objective quantification method, is expected to yield superior inter- and intra-observer agreement. Our future work will focus on utilizing the Agatston score to quantify CAC burden on non-contrast, non-gated chest CT to define more objective thresholds for guiding coronary CTA referrals, and to explore more reliable assessment methodologies and risk stratification criteria. Secondly, the number of participants included in this study was small and from a single center, so the conclusions of this study cannot be directly generalized to all populations. Thirdly, this study included only those who underwent coronary angiography, and the overall prevalence of cases was high.
Conclusions
In this study, when the CAC score on non-gated chest CT was severe, coronary CTA showed significantly reduced diagnostic performance for obstructive CAD, with lower AUC and decreased NPV. It is further inferred that coronary CTA is less effective in providing accurate stenosis assessment and coronary angiography should be considered if luminal severity will change patient management. However, the cut-off values for semi-quantitative CAC scoring remain to be clearly defined through future studies.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-291/rc
Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-291/dss
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-291/coif). Y.X. is an employee of Canon Medical Systems (China) Co., Ltd. and the company has no conflicts of interest related to this study. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Beijing Friendship Hospital ethics committee (approval No. 2024-P2-380-01) and individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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