|Year : 2020 | Volume
| Issue : 3 | Page : 468-473
Role of coronary artery calcium score in prediction of coronary artery stenosis in symptomatic patients with suspected coronary artery disease
Eman Rashed Zaki, Islam Shawky Abdel-Aziz, Mona Sallam Ismail, Hanaa Mohamed Fereig
Department of Cardiology, Faculty of Medicine (for Girls), Al Azhar University, Cairo, Egypt
|Date of Submission||24-Jun-2020|
|Date of Decision||10-Jul-2020|
|Date of Acceptance||14-Jul-2020|
|Date of Web Publication||2-Oct-2020|
Mona Sallam Ismail
Assistant Lecturer Cardiology, Department, Faculty of Medicine for Girls, Al-Azhar Univerisity, Cairo, Matbaa Faysal, Al Omra Street, Building 23, Flat 8, 1 phase, Giza, 12511
Source of Support: None, Conflict of Interest: None
Introduction The coronary artery calcium (CAC) score has been proposed as an alternative approach for stratifying cardiovascular risk.
Aim To assess the role of CAC score in prediction of coronary stenosis in symptomatic patients with intermediate probability for coronary artery disease (CAD).
Patients and methods A total of 80 symptomatic patients with intermediate probability for CAD underwent thorough history taking and clinical examination. Computed tomographic (CT) scan was done for all patients. A total of 48 (60%) patients with CAC score less than 400 HU (group A) underwent CT angiography: 30 (62.5%) patients had significant coronary stenosis (SCS) and were referred to invasive coronary angiography (ICA), whereas 18 (37.5%) patients had no SCS. Overall, 32 (40%) patients with CAC score more than 400 HU (group B) were referred directly for ICA.
Results ICA for 62 patients was performed: 30 (62.5%) patients were referred from group A, and all had SCS (100%), whereas 30 (93.7%) patients of 32 referred from group B had SCS. Using logistic regression analysis, CAC score was the only predictor of SCS (P=0.024). Receiver operating characteristic curve data revealed CAC more than 311.2 HU as a cutoff point for prediction of SCS, with specificity of 85.0%, sensitivity of 63.3%, and area under the curve of 74.7%. CT angiography sensitivity for detection of stenosis less than or equal to 50%, stenosis more than 50%, and stenosis more than 70% was 73, 62.5, and 94%, respectively; specificity of 96.8, 99.4, and 99.4%, respectively; and overall accuracy of 85.0, 81, and 96.9%, respectively, with negative predictive value to rule out SCS 99%.
Conclusion CAC score is predictive for the presence of SCS in patients, with intermediate probability for CAD.
Keywords: coronary artery calcium, computed tomographic coronary angiography, invasive coronary angiography, significant coronary stenosis
|How to cite this article:|
Zaki ER, Abdel-Aziz IS, Ismail MS, Fereig HM. Role of coronary artery calcium score in prediction of coronary artery stenosis in symptomatic patients with suspected coronary artery disease. Sci J Al-Azhar Med Fac Girls 2020;4:468-73
|How to cite this URL:|
Zaki ER, Abdel-Aziz IS, Ismail MS, Fereig HM. Role of coronary artery calcium score in prediction of coronary artery stenosis in symptomatic patients with suspected coronary artery disease. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 26];4:468-73. Available from: http://www.sjamf.eg.net/text.asp?2020/4/3/468/296958
| Introduction|| |
The presence of coronary artery calcium (CAC) has long been associated with an increased risk of cardiovascular mortality .
The clinical application of CAC scoring had been supported by evidence that the absence of calcium reliably excludes obstructive coronary artery stenosis  and that the amount of CAC is a strong predictor for risk assessment of myocardial infarction and sudden cardiac death independent of conventional coronary risk factors .
| Aim|| |
The aim is to assess the role of CAC score in prediction of coronary stenosis in symptomatic patients with intermediate probability for coronary artery disease (CAD).
| Patients and methods|| |
This is a prospective study carried out between April 2015 and April 2018 at Kobry El Koba Military Hospital. All the subjects had been informed about the study and written consents had been taken.
Symptomatic patients with intermediate pretest probability for CAD (likelihood of CAD >10% and <90% based on age, sex, and characteristic of chest pain according to diamond and Forrester risk model) , with nonconclusive ECG changes for ischemic heart disease (IHD) and normal cardiac biomarkers were included.
The following were the exclusion criteria:
- Patients known to have established CAD [previous myocardial infarction (MI) or coronary intervention].
- Patients with elevated serum creatinine (>1.4 mg/dl).
- Presence of arrhythmias (irregular heart rate).
- Severe allergic reaction to contrast media.
- Contraindications to radiation exposure.
- Respiratory impairment (inability to withhold breathing).
This series had a predetermined study protocol. All patients were scanned for CAC score. Patients with CAC score less than 400 HU (group A) were referred to invasive coronary angiography (ICA) if a significant coronary stenosis (SCS) was detected upon computed tomographic angiographic (CTA), whereas patients with total CAC score more than 400 HU (group B) were referred directly for ICA.
All patients received thorough clinical assessment including history of chest pain, assessment of conventional risk factors for CAD together with CAC scoring using the local CT protocol, drug history, examination, surface ECG, and echocardiographic examination.
All the subjects had been informed about the study, and written consents had been taken.
Multidetector computed tomographic angiography
The CT scan was performed utilizing a dual-source scanner (64 Siemens Somatom Definition and Definition Flash; Siemens, Siemens Medical Solutions A44A, Forchheim, Germany). Anteroposterior scanogram was obtained using low-dose, low-resolution spiral CT imaging of the chest (120 kV, 850 mA).
Coronary artery calcium scan
It was undertaken with the patient in the supine position. High-resolution scanning of the heart was begun at the level of the bifurcation of the main pulmonary artery and proceeded caudally through the cardiac apex. Breath-hold time was restricted to 20 s. The scan was performed in a prospectively ECG-triggered mode with 2.5–3.0-mm-thick axial images with an image acquisition time of 100–200 ms. The total CAC score was computed from all calcified lesions by means of Agatston et al.  score.
Computed tomographic coronary angiography acquisition
Heart rate was controlled to less than 75 bpm using beta-blockers. Semiautomated determination of the starting time using the ‘Bolus-tracing technique’ was used in all patients. When the density within the ascending aorta exceeds 100 HU, the scanning is triggered with a delay of further 3 s. Scan was performed using a dual-source 64-slice scanner (64×0.625 mm collimation with a tube rotation time of 400 ms, tube voltage of 120 kV/100 kV and current of 400 mA). Dose modulation was attained with ‘electrocardiographic gating’ for maximum gantry delivery 40–90% during the R-R interval.
A bolus of 60–90 ml of high-concentration contrast was administered intravenously at 5 ml/s, followed by 50 ml of normal saline infusion. Dose modulation was attained, and reconstructions were done in the diastolic phase (75% of the R-R interval) and systolic phase (40%). The data sets were then displayed and analyzed on dedicated software platforms (Siemens Medical Solutions VA44A, Forchheim, Germany). Stenosis was considered significant if it causes more than or equal to 50% stenosis of the left main coronary and/or more than or equal to 70% stenosis of the other major coronary beds .
Invasive coronary angiography
Routine ICA was done, and multiple views were taken. Evaluation of the CA was performed by two experienced readers blinded to the results of CTA using the software (Siemens AXIOM Artist dTA VB 35 workstation, Forchheim, Germany) in all coronary segments using at least two orthogonal views. Stenosis was considered significant if it causes more than or equal to 50% stenosis of the left main coronary and/or more than or equal to 70% stenosis of the other coronary branches, which is detected by visual inspection .
Data were collected, revised, coded, and entered to the Statistical Package for the Social Science (IBM SPSS), version 23 (IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). The value of CAC score was distributed in two groups: group A with CAC score less than 400 HU and group B with CAC score more than 400 HU. Logistic regression analysis was used to asses association between total CAC and coronary stenosis adjusted for risk factors. Receiver operator characteristic curve analysis was used to determine the optimal cutoff point for CAC score, with its sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under the curve (AUC). Gold standard test was used for determination of the sensitivity, specificity, positive prediction value, NPV, and overall accuracy of the CTA for detection of different grades of coronary arteries stenosis according to the ICA as a gold standard. P value less than 0.05 was considered significant.
| Results|| |
The study sample included five (6.25%) females and 75 (93.75%) males, with a mean age of 60±8 years.
They were divided according to CAC score into two groups.
- Group A: 48 patients with total CAC score less than 400 HU.
- Group B: 32 patients with total CAC score more than 400 HU.
There was no statistically significant difference between both groups regarding conventional CAD risk factors, clinical presentation, and 12-lead ECG.
Regarding echocardiography, there was a statistically significant reduction in mean E/A ratio in group B patients compared with group A (P=0.007) ([Table 1]).
A higher percentage of three-vessel disease (21%) was found in group B patients than in group A (7%).
Coronary artery calcium score and prediction of significant coronary stenosis
Multivariate logistic regression analysis revealed a statistical significant association between the total CAC score and the SCS [>50% left main (LM) and >70% in left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA)] detected by ICA irrespective of other CAD risk factors [P=0.02 and odds ratio (95% confidence interval) 1.003 (1–1.005)].
In our study sample using the receiver operator characteristic curve analysis, the cutoff value for predilection of SCS was CAC score more than 311.2 HU, with a sensitivity of 63.3%, specificity of 85.0%, and AUC of 74.7%.
Data analysis of computed tomographic angiography of group A in relation to invasive coronary angiography
The overall sensitivity of CTA for the detection of stenosis less than or equal to 50%, stenosis more than 50%, and stenosis more than 70% was 73, 62.5, and 94%, respectively; the overall specificity was 96.8, 99.4, and 99.4%, respectively; and the overall accuracy was 85.0, 81, and 96.9%, respectively ([Table 2], [Figure 1] and [Figure 2]).
|Table 2 The overall sensitivity, specificity, and diagnostic accuracy of computed tomographic coronary angiography for detection of different grades of coronary arteries stenosis|
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|Figure 2 ROC analysis for CAC score as a predictor for significant coronary stenosis. CAC, coronary artery calcium; ROC, receiver operating characteristic.|
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| Discussion|| |
Our study was conducted upon 80 patients who divided according to CAC score into group A (48) patients with CAC score less than 400 HU and group B (32) patients with CAC score more than 400 HU.
CAC scoring has been evaluated as a screening test for CAD in asymptomatic patients  and there are several large studies that demonstrate its role for further risk stratification after assessment of conventional risk factors , although a few studies have investigated CAC as a diagnostic test in symptomatic patients .
In our study, the mean age was 60.48±8.9 years in group A patients and 61.28±7.1 in group B. The age range in both groups was from 40 to 70 years, which was slightly lower to that observed by Nicoll et al. , who studied 5515 symptomatic patients in Europe (mean age, 60±12; range, 31–93 years). This age range furthermore reinforces the observation conducted by McClelland et al.  that CAC score increased with age. However, no statistical difference in age was found in our study sample between both groups.
All patients had atypical chest pain except only two patients who were presented by typical chest pain fulfilling intermediate pretest probability for CAD according to Diamond and Forester risk model, and none of our studied patients had an ECG change conclusive for IHD.
In our study, we found that patients with high CAC score more than 400 HU (group B) had a significant reduction in mean E/A ratio (P=0.007).
Guilherme et al.  reported that high CAC score in middle age was related to higher LV mass and higher LV end diastolic volume (P=0.007), higher LA volume (P=0.009), and higher E/e’ (P=0.014) and concluded that a high CAC score is associated with higher LV mass, higher volumes, and worse LV diastolic function, which can explain our finding.
In our study using linear regression analysis, the total CAC score was highly predictive for SCS (>50% LM and >70% in LAD, LCX, and RCA) detected by ICA irrespective of other CAD risk factors (P=0.024). Moreover, a higher number (93.8%) of patients among group B (CAC score>400) were found to have significant CAD.
Our finding in patients with intermediate probability for CAD go along with Nicoll et al. , who studied 5515 symptomatic patients and reported that using multivariate binary logistic regression analysis the CAC score was the most powerful predictor of significant coronary artery stenosis (P<0.001) in patients with intermediate risk for CAD.
Moreover, our results were concordant with Almasi et al. , who studied 202 patients, using linear regression model and in the presence of baseline parameters, including demographic data, left ventricular ejection fraction, lipid profile, BMI, and blood pressure, and they found that CAC score was the main determinant of the severity of coronary artery stenosis (P<0.001).
Our results were in agreement with Fernandez-Friera et al.  who reported that the CAC score has been shown to be predictive of obstructive CAD independent of cardiovascular risk factors, and despite that, it is far more practical to interpret the CAC score in association with the presence of known cardiovascular risk factors. Van Werkhoven et al.  demonstrated that the likelihood of significant coronary artery stenosis was influenced not only by CAC score but also by pretest likelihood based on the Diamond and Forrester method. The same protocol was used in our study for determination of patients pretest probability for CAD.
In another way of angiographic data analysis, we found that a higher percentage of three-vessel disease (21%) was found in group B (CAC>400 HU) patients than in group A (7%), which goes with the results of Rosen et al.  in a subanalysis of MESA study, which involved 178 patients who underwent ICA, and reported that CAC score could predict the severity of coronary stenosis with a higher prevalence of SCS and more incidence of LM and multivessel disease among patients with CAC score more than 400 HU.
In our present study, the cutoff value for prediction of SCS was 311.2 HU, with considerable specificity of 85.0% and good predictive value of 92.37%.Our results were concordant with Almasi et al. , who reported a cutoff value of 350 HU for predication of significant coronary artery stenosis, and they concluded that this score could be used as an additional filter before CCTA among patients with intermediate risk for CAD.
Comparison between CTA and ICA in group A revealed that the specificity of CTA for detection of stenosis more than or equal to 50%, stenosis more than 50%, and more than 70% was 96.8, 99.4, and 99.4%, respectively; the sensitivity was 73, 62.5, and 94%, respectively; and the overall accuracy was 85.0, 81, and 96.9%, respectively.
Our results were concordant with Mannan et al. , who reported a sensitivity of 90, 83.8, and 80.7% for the detection of stenosis less than or equal to 50%, stenosis more than 50%, and more than 70%, respectively, and a specificity of 96.5, 98.4, and 98.3, respectively .
In our study, the NPV of 64-slice MDCT to rule out obstructive CAD was 93% for the diagnosis of less than or equal to 50% stenosis, 99% for more than 50% stenosis, and 99% for more than 70% stenosis.
Our results were concordant with Mannan et al. , who reported NPV of 99.1% for the diagnosis of less than or equal to 50% stenosis, 97.6% for more than 50% stenosis, and 97.9% for more than 75% stenosis.
The study was limited by the small number of patients and the selection of patients for testing within a military institute with limited number of referred female patients.
| Conclusion|| |
CAC score was highly predictive for the presence of significant coronary artery stenosis in symptomatic patients with intermediate probability for CAD irrespective of other CAD risk factors.
The cutoff value of the total CAC score for prediction of SCS was more than 311.2 HU, with specificity of 85.0%, positive predictive value of 93%, sensitivity 63.3%, and AUC 74.7%.
CT coronary angiography allows the identification of a SCS with excellent accuracy and high NPVs.
Further large-scale trials are required in intermediate-risk patients for CAD to probably detect the absolute predictive value of CAC score over other risk factors and to establish the utility of CAC score for triaging those patient populations into groups that may and may not benefit from further invasive diagnostic test.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]