The role and diagnostic value of assessing the degree of coronary arteries calcification for predicting the severity of coronary heart disease

Materials and methods. According to the purpose of the study, 46 patients were included: 32 (69.6 %) males and 14 (30.4 %) females. The average age of the patients was 59.0 ± 9.8 years, height – 172 ± 9 cm, weight – 85.6 ± 12.9 kg, body mass index (BMI) – 28.6 ± 4.13, body surface area (BSA) – 1.98 ± 0.17 m2. Demographic and clinical variables were analyzed using descriptive statistics. Independent t-tests were conducted between two groups of patients (Agatston index ≥400 and <400), using P < 0.05 as a significant value. Pearson correlation coefficient was employed to determine independent coronary calcium predictors using P < 0.05 as a significant value.

Coronary heart disease (CHD) is one of the leading mortality causes [1]. According to the latest guidelines, coronary computed tomography angiography (CCTA) is one of the main non-invasive methods for diagnosis of CHD, which allows for quantification of stenosis severity and the characterization of stenotic lesions [2].
A sufficient number of studies has shown that the severity of coronary artery (CA) lesions, assessed on the SYNTAX scale, allows to determine the prognosis associated with the risk of major adverse cardiovascular events (MACE). Further parameters defining the type of surgical intervention and periprocedural risks, taking into account complex lesions of CA, including bifurcation, total chronic occlusion, intraluminal thrombi, calcification and diffuse lesion [3,4].
The coronary artery calcium score (CACS) has predictive value for future coronary events [5,6], but its accuracy for prediction of obstructive coronary artery disease is rather weak. In contrast to CACS, CCTA is a non-invasive method for a more accurate qualitative and quantitative determination of coronary calcium, which has been verified as a lesion with a tomographic optical density of more than 130 Hounsfield units, with the area of ≥1 mm 2 [7,8]. The amount of coronary calcium detected by CCTA correlates with histologically determined atherosclerotic plaques and makes up to 20 % of their total amount [9]. Coronary artery calcium is a highly specific marker of atherosclerosis; it integrates all the risk factors throughout a person's life [10,11], however, the amount of non-calcified fibroatheroma can only be detected by CCTA and is missed by CACS. The correlation between the total coronary calcium score (CACS), measured with Agatston scoring system, and the severity of coronary artery disease are contradictory, weak and unreliable [12,13].
Thus, the feasibility of using data on the degree of calcification of coronary arteries in cardiovascular risk stratification, along with traditional risk factors such as gender, age, smoking, lipid levels, diabetes mellitus and family history, requires further study.

Aim
It is to study the role, diagnostic value and dependence of coronary artery calcification on the degree of stenotic lesion of the coronary arteries and anthropometric parameters in patients with coronary artery disease examined by computed tomography.

Materials and methods
The data obtained from patients, who had undergone computed tomography (CT) screening of coronary arteries calcification and CCTA in the period between 2018-2019, were analyzed. The inclusion criteria were signing of informed consent, the presence of coronary heart disease, the presence of calcified atherosclerotic plaques in the coronary arteries walls. The exclusion criteria were the absence of coronary artery atherosclerosis as seen on computed tomography, and the presence of artefacts that compromised the interpretation of CCTA data (motion, pulse, respiratory ones).
According to the purpose of the study, 46 patients were included: 32 males (69.6 %) and 14 females (30.4 %). The average age of the patients was 59.0 ± 9.8 years, height -172 ± 9 cm, weight -85.6 ± 12.9 kg, body Computer tomography of the heart and coronary arteries was performed with multi-detector 64-pixel computer tomographic scanner Aquilion TSX 101A (Toshiba, Japan). The research was performed in ECG-synchronized mode, with a specific heart rate up to 60 beats per minute. At the first stage, for coronary artery calcium score (CACS) screening, low-dose step-by-step scanning protocol was employed, which was performed in craniocaudal direction from tracheal bifurcation level to diaphragm level, with partition thickness of 3 mm, without intravenous administration of contrast agent (native scanning). At the following stage, a standard MDCT-coronary angiography (CCTA) was performed with retrospective reconstruction of the raw data obtained. Postprocessing was performed with Vitrea workstation (Vital images).
Evaluation of coronary artery calcification from CACS scans was carried out by means of Calcium scoring CT software, which is a part of the software package for the workstation, in semiautomatic mode: the route of each artery was defined manually, whereas there was automatic calculation of coronary calcium score with Agatston scoring system, as well as of the volume of calcified atherosclerotic plaques.
The analysis of stenotic or occlusal lesion of coronary arteries was performed on CCTA datasets with the use of axial partitions, multiple planar and curvilinear reformations, and 3D reconstructions.
The coronary artery lesion index was determined using anatomical SYNTAX score (SYNTAX score) using an online calculator (https://syntaxscore2020.com/).
Demographic and clinical variables were analyzed using descriptive statistics. The Shapiro-Wilk test was used to determine if a data set is well-modeled by a normal distribution. The data set that was normally distributed presented as average and standard deviation (М ± m). Independent t-tests were conducted between two groups of patients (Agatston index ≥400 and <400), using P < 0.05 as a significant value. In case of deviation from the normal distribution, data was presented as median and interquartile range (Me [Q 25 ; Q 75 ]) and Mann-Whitney U-test was used. Spearman's rank correlation coefficient was employed to determine independent coronary calcium predictors using P < 0.05 as a significant value. Analyzes were performed with Statistica 13.0 software package (StatSoft Inc., No. JPZ8041382130ARCN10-J).

Results
According to the purpose of the study and the results of CCTA, the patients were divided into 2 groups: Group 1 included patients with a pronounced degree of coronary arteries calcification and Agatston score level ≥400, and Group 2 comprised patients with moderate and minimal coronary arteries calcification with Agatston score level <400. The obtained data are presented in Table 1.
Thus, in both groups there was the same number of patients, while in Group 1 males significantly prevailed (P < 0.05), and in Group 2 there were no gender differences.
According to patients' average weight, height, BSA, and BMI, there were no significant differences between the groups; all patients were overweight.
According to the results of the age analysis, significant differences were found among both groups of patients (P = 0.02). However, there was no significant correlation of age with the Agatston index (r = 0.22, P > 0.05).
Notable differences in the number of affected coronary arteries between Groups 1 and 2 with an Agatston index ≥400 and <400 (P < 0.01) were found. A significant positive correlation was revealed between the number of stenosed coronary arteries and the Agatston index (r = 0.52, P < 0.01) in both groups, which is shown in Fig. 1.
Considerable differences were found in Groups 1 and 2 when analyzing SYNTAX score level. So, SYNTAX score in patients of Group 1 was 29.08 ± 9.44, which corresponded to the indications for coronary artery bypass grafting and was associated with predictions of cardiac mortality and the risk of major adverse cardiovascular events ranging from 10.9 % to 12.0 % (against up to 23.4 % during percutaneous coronary intervention (PCI)). Whereas the SYNTAX score in patients of Group 2 was 14.39 ± 5.67, which corresponded to the indications for PCI and was associated with predictions of cardiac mortality and the risk of major adverse cardiovascular events at 13.6 % [4]. During the correlation analysis, a significant moderate positive correlation (Fig. 2) of the SYNTAX score level with Agatston index (r = 0.69, P < 0.01) was revealed.

Discussion
Data on coronary artery calcification provided by CCTA have both diagnostic and prognostic information in addition to the conventional risk factors for coronary artery disease. The presence of calcium confirms coronary atherosclerosis and is associated with an increased risk of coronary events. According to the data obtained, male patients are more susceptible to pronounced coronary arteries calcification (32 versus 14), with a greater tendency to multivessel lesion. This suggests a possibly more aggressive course of atherosclerosis in males, which is confirmed by the works of other authors [14].
In the course of data analysis, it was found that the degree of coronary calcification is higher in patients of older age groups (P = 0.02), which is explained by the progression of atherosclerosis, with a correlation in the number of affected coronary arteries and the complexity of their lesions, expressed in the estimation by SYNTAX score, which leads to higher risks of major adverse cardiovascular events.
The results of our study are comparable with previous reports that age and male gender are independently associated with coronary calcium levels. The correlation between coronary calcification and endothelial dysfunction has also been demonstrated, as well as with impaired myocardial perfusion in patients with angiographic intact coronary arteries [15][16][17]. Therefore, altered coronary blood flow in the presence of coronary calcification affects the development and formation of atherosclerotic plaques, which are the main determinants of the development of severe forms of coronary artery disease. Besides, coronary calcification is one of the predictors of obstructive coronary artery disease and has predictive value for future coronary events.
Generally, coronary calcium is limited to subintimal space and may occur nearly from the 20 th year of a person's life. The calcification of atherosclerotic plaque increases with aging and atherosclerosis progression. Therefore, coronary calcium is a marker of coronary atherosclerosis [18]. Previous studies have examined the association of coronary artery disease with coronary calcium in patients with asymptomatic disease. The prognostic value of calcium screening and its independence from traditional risk factors was shown [18]. Consequently, it is suggested to use coronary calcium levels as a predictor of CHD [19,20]. There are also studies that have investigated the importance of coronary calcium for predicting the severity of coronary heart disease [21,22], but our results do not contradict the results of these studies, although different methods have been employed.

Conclusions
1. The degree of coronary arteries calcification with Agatston score ≥400 is an independent predictor of severe coronary heart disease with multivessel lesion of the coronary arteries.
2. The degree of calcification of coronary arteries with Agatston score ≥400 is more common in males.
3. Height, weight, BMI and BSA do not influence the degree of coronary calcification arteries and Agatston score level.
Prospects for further research. Further research may be focused on elucidating the genotype influence on Agatston score level. Оригінальні дослідження