Diagnostic accuracy of coronary artery calcium score for excluding obstructive coronary artery disease

Manish Bansal; Deepak Sharma; Ravi R Kasliwal

doi:10.4103/jcpc.jcpc_1_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 11 | Issue : 2 | Page : 44-49

Diagnostic accuracy of coronary artery calcium score for excluding obstructive coronary artery disease

Manish Bansal¹, Deepak Sharma², Ravi R Kasliwal¹
¹ Department of Clinical and Preventive Cardiology, Medanta - The Medicity, Gurgaon, Haryana, India
² Department of Clinical Research, Medanta - The Medicity, Gurgaon, Haryana, India

Date of Submission	03-Jan-2022
Date of Decision	21-Jan-2022
Date of Acceptance	24-Jan-2022
Date of Web Publication	24-Jun-2022

Correspondence Address:
MD, DNB Cardiology Manish Bansal
MD, DNB Cardiology, FACC, FASE, Department of Clinical and Preventive Cardiology, Medanta Heart Institute, Medanta - The Medicity, Gurgaon - 122 001, Haryana
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jcpc.jcpc_1_22

Abstract

Background: Studies in western populations have shown that zero coronary artery calcium score (CACS) is associated with a very low prevalence of obstructive coronary artery disease (CAD), even in patients presenting with chest pain. However, no data are available about the relationship between CACS and coronary artery plaques among Indian subjects. Methods: A total of 380 subjects undergoing comprehensive health check, including computed tomography coronary angiography (CTCA), at a tertiary care center in North India were included. The distribution of CACS was correlated with the coronary plaque burden and with the clinical and laboratory investigation findings. Results: The mean age of the subjects was 52.8 ± 10.0 years, and 71.8% were men. The median CACS value in the study population was 0 (interquartile range 0–4.3). Two-third of all the subjects had zero CACS and 91 (23.9%) had CACS between 1 and 99. Nonobstructive and obstructive (>50% stenosis) plaques were found in 106 (27.9%) and 24 (6.3%) subjects, respectively. Only 5.9% of the subjects with zero CACS had any coronary plaque and only 1.2% had obstructive plaques, yielding zero CACS 98.8% negative predictive value for excluding obstructive disease. Conclusion: This study shows that similar to the western populations, in Indian subjects also, zero CACS is associated with a very low prevalence of obstructive CAD and has excellent negative predictive value for ruling it out. Further large studies in diverse patient subgroups, including those with stable or unstable chest pain, are required to validate these findings.

Keywords: Chest pain, coronary atherosclerosis, functional testing, power of zero, stress test

How to cite this article:
Bansal M, Sharma D, Kasliwal RR. Diagnostic accuracy of coronary artery calcium score for excluding obstructive coronary artery disease. J Clin Prev Cardiol 2022;11:44-9

How to cite this URL:
Bansal M, Sharma D, Kasliwal RR. Diagnostic accuracy of coronary artery calcium score for excluding obstructive coronary artery disease. J Clin Prev Cardiol [serial online] 2022 [cited 2023 Jun 9];11:44-9. Available from: https://www.jcpconline.org/text.asp?2022/11/2/44/348079

Introduction

Over the last two decades, coronary artery calcium score (CACS) has emerged as a powerful predictor of the risk of future cardiovascular (CV) events among subjects without documented atherosclerotic CV disease (ASCVD). The individuals with zero CACS have an extremely low risk of CV events over the next 5–10 years, whereas those with CACS >100 experience event rates similar to those seen in patients with known ASCVD.^{[1],[2],[3],[4],[5],[6],[7],[8]}

However, while the utility of CACS for risk prediction in asymptomatic individuals is now well established, its role in the prediction of obstructive coronary artery disease (CAD) in symptomatic patients remains debated. It has been argued that calcification is a late event in the process of atherogenesis, and hence, CACS may not accurately predict early, soft but stenotic plaques.^[9],[10] Conversely, there are many individuals who have diffuse atherosclerosis with high CACS but no obstructive disease.^[11]

Interestingly, recent large studies have shown that zero CACS is highly accurate even for excluding obstructive CAD in patients presenting with acute chest pain.^[12],[13] This has prompted calls for using CACS for triaging patients with chest pain in the emergency rooms as well as in the outpatient setting.^[14] Such an approach, however, may have some challenges in young subjects who are more likely to have noncalcific plaques.^[14] This issue is particularly relevant for Indians because CAD in Indians tends to occur at least 10–15 years earlier than their western counterparts.^[15],[16] Since there are only very limited data available about CACS in Indians,^[17] we sought this study to assess relationship of CACS with coronary plaques among Indian subjects.

Methods

This was a retrospective study conducted at a tertiary care center in North India. All the subjects undergoing computed tomography coronary angiography (CTCA) as part of their comprehensive health check during the period January 1, 2019–December 31, 2019, were included in the study. The subjects with known obstructive CAD, chronic kidney disease, chronic liver disease, and those with incomplete data were excluded.

For all subjects, clinical details, laboratory investigation findings, and CTCA findings were extracted from their medical records. Clinical details included information about their CV risk factors, body mass index, heart rate, and blood pressure. Hypertension (HT) was diagnosed if the patient had reported a previous diagnosis of the same or was using antihypertensive medications. Diabetes mellitus (DM) was diagnosed if there was a history of the same, the patient was on antihyperglycemic medications or if fasting blood glucose was >126 mg/dL or glycosylated hemoglobin >6.5%. Any cigarette smoking during the preceding 1 month was coded as current smoking, whereas subjects with any history of regular smoking in the past were labeled as ex-smokers.^[17] Laboratory investigations included measurement of fasting blood glucose, glycosylated hemoglobin, and fasting lipid profile.

All subjects underwent CTCA as part of their health check. CTCA was performed on a 256-slice multidetector CT scanner. CACS estimation was performed using the Agatston method with a slice thickness of 3.0 mm.^[18] For assessment of plaques, scanning was done in a single breath-hold, with a slice thickness of 0.6 mm. The image interpretation was performed as per the Society of Cardiovascular Computed Tomography guidelines.^[19] Plaques causing <50% luminal diameter stenosis were considered nonobstructive, whereas those causing >50% stenosis in any of the major epicardial coronary artery segments were considered obstructive.

Statistical analysis

The baseline characteristics and other descriptive variables were summarized using standard statistical tools such as mean ± standard deviation, median, and interquartile range, or counts and proportions as appropriate. The categorical variables were compared using Chi-square test and continuous variables using independent t-test. Two-sided P < 0.05 was considered statistically significant. All analyses were performed using IBP SPSS statistics version 23.0 (IBM, Armonk, NY, USA).

Results

A total of 380 subjects were included in this study. The mean age was 52.8 ± 10.0 years and 71.8% were men.

[Table 1] summarizes clinical and laboratory characteristics of the study subjects. Slightly less than half (45.5%) of all the subjects had HT, 35.5% had DM, and 15.7% had history of current or previous smoking. Majority (79.2%) had body-mass index >25.0 kg/m.^[2] Low-density lipoprotein cholesterol was >100 mg/dL in 63.4% subjects and >70 mg/dL in 87.6% subjects.

Table 1: Clinical and laboratory characteristics of the study population (n=380)

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Coronary artery calcium score distribution

The median CACS value in the study population was 0 (interquartile range 0–4.3) [Table 2]. Two-third of the study participants had zero CACS and 91 (23.9%) had CACS between 1 and 99. Compared with subjects with CACS >0, those with zero CACS were younger and had lower prevalence of HT and DM with lower mean values of systolic blood pressure and fasting blood glucose [Table 3].

Table 2: Compute tomography coronary angiography findings in the study population (n=380)

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Table 3: Clinical and laboratory characteristics of the study population in relation to coronary atherosclerosis findings (n=380)

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coronary plaque distribution

Of the 380 subjects, 250 (65.8%) had no identifiable coronary plaque [Table 2]. Among the remaining 130 (34.2%) subjects, 106 (27.9%) had nonobstructive plaques and 24 (6.3%) had obstructive plaques. Nine (2.4%) subjects had plaques causing >70% stenosis. Nearly two-third (15 or 24) of those with obstructive disease had single-vessel disease, whereas the remaining had multivessel involvement [Table 2]. Similar to the patients with nonzero CACS, the patients with coronary plaques were older and had a higher prevalence of HT and DM [Table 3].

Relationship between coronary artery calcium score and coronary plaques

Only 5.9% of the subjects with zero CACS had any coronary plaque and only 1.2% had obstructive disease [Table 4] and [Figure 1]. Conversely, among subjects with nonzero CACS, 115 (90.6%) had one or more plaques and 21 (16.5%) had obstructive plaques. Thus, zero CACS had 87.5% sensitivity for detecting obstructive disease with negative predictive value of 98.8%. The negative predictive value for excluding any plaque was 94.1%. No difference was found in the negative predictive value of CACS in patients <40 years of age, 40–59 years and >60 years of age.

Table 4: Coronary artery calcium score in relation to coronary plaques in the study population (n=380)

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Figure 1: Severity and distribution of coronary plaques in subjects with zero and non-zero coronary artery calcium score. CACS- coronary artery calcium score

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Among subjects with CACS >100, all had coronary plaques, and in one-third of them, there was at least one obstructive plaque causing >50% stenosis.

Discussion

Chest pain is one of the most common reasons for presentation to the hospital, both in the emergency room and in the outpatient setting. Although CAD is identified as the cause of chest pain in <5%–10% of all such cases,^[20] most patients undergo a series of investigations to rule out obstructive CAD because of the fear of missing the diagnosis with potentially deleterious consequences. In the outpatient setting, guidelines recommend assessment of pretest probability based on clinical features, followed by no testing, functional testing, or anatomic imaging, as appropriate.^[21] On the other hand, in the emergency room, various risk algorithms incorporating clinical parameters, electrocardiographic findings, and cardiac markers are used for initial risk stratification, followed by some form of further cardiac testing in those deemed to be at low-intermediate risk and coronary angiography in those considered to be at high risk.^[21] However, all these evaluation strategies have inherent limitations, resulting in frequent overinvestigation and wastage of resources. In this scenario, a diagnostic tool that can reliably exclude obstructive CAD is highly desirable.

Over the last two decades, CACS has emerged as a powerful predictor of the risk of future CV events. CACS estimation is a simple test to perform, with no need for iodinated contrast, <10-15 min of room time, <1 millisievert radiation dose and relatively low cost.^[22] Any multipurpose multidetector CT scanner can be used for CACS estimation.

Numerous studies have shown that zero CACS is associated with a very low risk of CV events in the near future, even in patients with multiple CV risk factors.^{[1],[2],[3],[4],[5],[6],[7],[8]} These observations have prompted the use of CACS as a gatekeeper for decisions regarding further testing in patients presenting with chest pain.^[14],[23] A recent large study evaluated the utility of CACS for this purpose in the emergency setting. A total of 5192 patients (mean age 53.5 ± 10.8 years) with suspected acute coronary syndrome (ACS) who were deemed to be at low to intermediate risk and who had undergone CTCA were included in this study.^[12] More than half (56%) of them had zero CACS. Among them, only 0.7% had obstructive CAD with 0.4% having >50%–69% stenosis and 0.3% having >70% stenosis. Another study included 826 consecutive patients (mean age 53 ± 11 years) with acute chest pain but without known CAD or initially elevated serum biomarkers.^[13] Of them, 7.9% were later confirmed as having ACS; further, 16% had ≥50% stenosis and 8.7% ≥70% stenosis. CACS was found to be zero in 54% of the subjects. In these patients with zero CACS, only 2 had ACS and 4 had >50% stenosis, yielding negative predictive values of 99.5% and 99.1% for ruling out ACS and obstructive CAD, respectively. Several other studies have shown similar findings.^{[24],[25],[26]} A meta-analysis of 8 such studies showed that zero CACS also had excellent prognostic value for predicting major adverse CV event (MACE) rates following discharge from the emergency room.^[27] The patients with zero CACS had a MACE rate of only 0.8%/year over a median follow-up of 10.5 months, which was 94% lower than the risk observed in patients with nonzero CACS (14.6%/year).

Several other studies have evaluated the diagnostic utility of CACS in stable chest pain.^{[5],[11],[23]} Mortensen et al. recently reported the relationship between CACS and coronary plaques and their respective prognostic utility in 23759 symptomatic patients (mean age 57 years) included in the Western Denmark Heart Registry.^[11] Only 5.7% of the 12771 subjects with zero CACS had obstructive CAD (>50% stenosis). Furthermore, for any given CACS value, the MACE rates were similar in patients with or without obstructive CAD.

These studies provide robust evidence to support the growing understanding that zero CACS implies very low likelihood of prevalent obstructive CAD and low risk of events in patients presenting with chest pain without previously documented CAD. Recognizing this evidence, the latest guideline for chest pain evaluation, published by the American College of Cardiology/American Heart Association Joint Committee, has incorporated CACS in the diagnostic algorithm.^[21] However, the diagnostic accuracy of CACS for predicting obstructive CAD among different ethnic groups with different CV epidemiology remains to be evaluated.

Indians are known to have a higher risk of ASCVD and tend to develop the disease at an earlier age as compared to the western populations.^[15],[16] These epidemiological differences may influence the diagnostic and prognostic value of CACS, and therefore, studies performed in Indian subjects are needed. Unfortunately, only one previous study published nearly two decades ago had evaluated CACS in Indian subjects.^[17] In view of this, the present study provides valuable contemporary information on this subject. Most of our observations were quite consistent with the findings reported in the western populations. We found that even in Indians, zero CACS had excellent negative predictive value for ruling out obstructive CAD. This excellent negative predictive value was seen even in young subjects <40 years of age. This is a reassuring finding and should lead to further research in this field and also greater adoption of CACS for chest pain evaluation, in accordance with the current guidelines.

Limitations

Our study included those subjects who were undergoing comprehensive health check and were not necessarily symptomatic. This resulted in a relatively lower prevalence of obstructive CAD in our study population, as compared to many of the previous studies in patients with chest pain.^[11],[12] This may have inflated the negative predictive value of zero CACS found in this study for excluding obstructive CAD. Therefore, further studies involving patients with stable or unstable chest pain are required to ascertain the true value of CACS for triaging such patients. Nevertheless, our study still provides an important message that the probability of finding obstructive CAD in patients with zero CACS is likely very low.

In our study, we did not correlate CTCA findings with functional testing or invasive coronary angiography. Hence, we could not confirm the actual anatomic severity or functional significance of the stenotic plaques detected on CTCA. However, this limitation is not unique to our study and has been there with most of the similar studies performed on this subject in the past.

Conclusion

Our study shows that similar to the western populations, in Indian subjects also, zero CACS is associated with a very low prevalence of obstructive CAD and has excellent negative predictive value for ruling it out. Further large studies in diverse patient subgroups, including those with stable or unstable chest pain, are required to validate these findings.

Financial support and sponsorship

Nil.

Conflicts of interest

Manish Bansal and Ravi R Kasliwal are editorial board members of the Journal of Clinical and Preventive Cardiology. The article was subject to the journal's standard procedures, with peer review handled independently of these editorial board members. There are no other conflicts of interest.

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