Significance of Coronary Calcium: Influence of Age, Diabetes, and Other Risk Factors

ABSTRACT IMAGE

INTRODUCTION

The detection of coronary calcium was recognized as a marker for atherosclerosis as early as 1940. But only by, 1990, its measurement was standardized on computed tomography (CT) scan and was named as Agatston score. The original Agatston score was designed for electron beam CT estimation of calcium over the coronaries but subsequently was adapted to the new generation multi-detector computerized tomography (MDCT) scanners.^[1] Over the next few years the Agatston score was validated as a reliable maker to detect the presence of atherosclerosis and elevated scores correlated with future cardiac events.^[2] At present, the CT coronary artery calcium (CAC) is an accepted parameter to predict the likelihood of obstructive coronary disease in asymptomatic patients.^[2] There are a few studies suggesting that the higher scores correlated with more aggressive coronary artery disease. It is a utility to monitor plaque progression while statin therapy is also recognized.^[3] Our study is aimed to find out if Agatston score can predict the extent of the coronary artery disease (CAD) and if its predictive value is influenced by age, diabetes, or other risk factors.

MATERIALS AND METHODS

All willing patients with symptoms suspecting coronary artery disease, those needing computerized tomography based coronary artery angiography (CT-CAG) for pre-operative evaluation and those needing screening of coronary artery disease referred for coronary CT angiography were included in the study. The study period was 18 months. Informed consent was obtained before examination. Patients were asked to fast 4 h and were not allowed to have caffeine for 12 h before examination. Metformin was suspended on the day of examination and at least 48 h after contrast administration. Patients were asked to continue other regular medications. History of allergy was obtained and appropriate precautions were taken. 18G catheter was put in the antecubital vein. Oral metoprolol 50–100 mg was given 1 h before scan if the heart rate was high. Heart rate was maintained at <65 b/min. Intravenous metoprolol was given immediately before examination if required to control HR. 400–800 mcg of nitroglycerine sublingual tablet 5 min before coronary angiogram (CAG) was routinely used. The patient was asked to hold breath for 5–10 s. Electro cardiogram (ECG)-gated prospective scanning was done from below arch to base of heart. Voltage of 120 kV and 560 mA was used. Scan was done on 128 slice CT Somatom Definition AS+. At a rate of 5–7 cc/per second of 350–370 mg/mL, 80–100 mL of non-ionic iodinated contrast was injected. Bolus tracking was done with attenuation of 100 HU in ascending aorta.

Calcium scoring (CAC) was obtained with software provided by Siemens. CAC of each coronary artery is summated to get the final score. Based on density, factor scores were given. multiplanar reconstruction (MPR), curved MPR, maximum intensity projection (MIP), and volume-rendered tomography (VRT) images were reconstructed. Overall, the extent of CAC was categorized as 0 – Absent CAC; 1–100; moderate – 101–300; Severe – 301–999, and extensive – >1000. Quantitative stenosis estimation was done on analysis of curved MRP images, followed by cross-sectional and longitudinal sections to measure the diameter and quantitate the stenosis. Those with more than 400 scores were excluded from the analysis.

Patients are divided into two groups based on the degree of stenosis – Group I: No atherosclerosis/non-obstructive lumen/narrowing <50% diameter stenosis and Group II: Obstructive lumen (>50% diameter stenosis). Patient are said to have significant CAD if any one or more than one epicardial vessel shows >75% diameter stenosis and the left main has >50% diameter stenosis.

RESULTS

There were 60 patients with 18 females (30%). The age ranged from 42 to 86 years. 26 (43%) were aged <50 years. 23 (38.3%) were diabetic patients. 27/60 (45%) had 3 or more risk factors. CAC values obtained in our study are detailed in Table 1. Eleven of the 60 (18.3%) had CAC > 100. Fifteen patients (25%) showed significant obstructive CAD. 10 of the 11 (91%) who had CAC > 100 showed significant CAD. Of the rest 49 with CAC < 100, only 5 (10%) showed significant CAD. The relationship between age and diabetic status was analyzed in Table 2. Among those >50 years, those with diabetes 12/18 (66%) showed significant CAC compared to 6/16 (37%) among the non-diabetics.

Among those <50 years of age, in those with CAC >100, 2/22 (9%) had CAD [Tables 1 and 3]. One is a diabetic with 2 other risk factors (RFs). His CAC was 52. Another male patient was non-diabetes but had 3 RF and CAC was 71. He showed significant CAD. In the group with significant CAD, the mean CAC was 206 as against 14.5 in those with insignificant CAD. Higher age, diabetes, and presence of >3 risk factors seem to be associated with higher CAC and significant CAD. The presence of significant CAD was directly correlated with the CAC value [Tables 4 and 5]. CT scan images of two illustrative cases from our study are illustrated below [Figures 1 and 2].

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Figure 1:

65 year old female patient with computed tomography coronary calcium score of 214. There is eccentric calcified plaque in the proximal left anterior descending artery causing a 50% block. She had 3 risk factors.

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Figure 2:

61 year-old male patient with calcium score of 131. There is no significant block on CT-coronary angiogram. He had 4 risk factors.

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DISCUSSION

Despite the introduction of several modifications, the traditional Agatston score remained simple and time-tested CAC to assess atherosclerotic burden. Expert committees continue to endorse its use for risk prediction of asymptomatic individuals, to decide on the need to start statins, and to decide on the need for depiction of coronary arteries and lesions.^[4] Age, diabetes, and other coronary risk factors influence the genesis and progression of atheromatous plaque. Hence, it is important to interpret the calcium score with respect to the age and presence of diabetes and other coronary risk factors when used to predict atherosclerosis in asymptomatic patients. Latest American Heart Association (AHA) guidelines recommended measuring CAC if the decision is uncertain in the age group of 40–75 years based on atherosclerotic cardiovascular disease (ASCVD) risk estimation to start statin therapy as primary prevention. Among those with intermediate risk, when the calcium score is zero, if there is no.

Diabetes, family history, or smoking statins are not recommended. With scores of 1–99 in persons above 55 years, statins are favored. When score is >100, statins are recommended.^[5]

In South-Asians, the atherosclerosis manifests at an earlier age, even in the absence of traditional risk factors.^[6] It is a common practice not to advise CAC as a screening test in individuals <50 years. In our study, we excluded those with symptoms or those with CAC >400. Eight out of 11 (72.7%) having high calcium scores have significant CAD, while 7 out of 49 (14.3%) have significant CAD with scores <100. Patients <50 years were 26 and rest were >50 years. In Coronary Artery Risk Development in Young Adults (2017), a prospective community-based study, it was observed that CAC of 100 or above is linked with high risk of mortality. Adults under the age of 50 years, who have any CAC found on CT scan, are at an increased risk of clinical coronary heart disease (CHD), CVD, and mortality even with low score.^[7] This correlates with our observation. We had four cases of significant CAD with CAC of 3–50 agaston units (AU). Four out of 60 patients are non-diabetic and had scores of 0–64 AU having significant CAD. Three of them have multiple risk factors. It suggests that even those below 50 years can have higher CAC if they have diabetes or multiple risk factors.

There are some limitations to the traditional CAC score. There are efforts to further enhance its validity by looking at its distribution pattern (diffuse or concentrated), total CAC lesions, mean density, and quantification of extra coronary calcification. Efforts are also focusing on the radiation involved without compromising the quality of reports. CAC is found to be a better prediction tool than high-sensitivity C-reactive protein (hs-CRP) or carotid–intima media thickness (CMT) for cardiovascular events.

The Multi-Ethnic Study of Atherosclerosis (MESA) had designed a coronary heart disease (CHD) score, by taking factors such as age, gender, CAC, race, diabetes, current smoking, family history of CHD, total cholesterol, high-density lipoprotein, systolic blood pressure, and use of hypertension/lipid-lowering medications. This predicts 10-year CHD risk and was found very useful for age ranges 45–85 years.^[7] We found that traditional CAC is simple to use and when correlated with age, presence of diabetes, or more than 3 risk factors, it can predict possible CAD in asymptomatic adult patients irrespective of their age. Our study is clinically relevant as the practice of requesting CT coronary calcium is growing. The cost of the test is about INR 1.5–2K and is often a part of master health check-up packages.

At present, newer trials are being conducted to fill the gaps in evidence for CAC-based primary prevention strategies.^[8] The DISCHARGE trial published in 2024 included 3561 patients with stable chest pain and randomized to either invasive coronary angiogram or CT angiogram. Those who had CAC score of 0 had very low incidence of major adverse cardiac events (MACE) (hazard ratio −0.08) compared to those with 400 or more score (hazard ratio −1). This study highlights the predictive role for MACE in patients with stable angina.^[9]

Our small observational study involving Indians suggested that the cut-off for initiating statins in those with CAC < 100 needs to be further lowered in diabetic patients or in presence of multiple other risk factors. Our study suggests a larger trial on this aspect. We also propose that whenever obstructive CAD is suspected in women <50 years in presence of diabetes or multiple risk factors CAC should be advocated, though it is not a common current practice.

CONCLUSION

CAC is a useful tool to predict presence of significant CAD, especially in individuals above 50 years more so in diabetic patients and those with more than 3 risk factors. In female patients <50 years, it may be a good practice to do CAC when they have diabetes and multiple risk factors.