Incidental Tomographic Findings of Coronary Artery Calcifications: A Prevalence Study in Southern Brazil

Introduction: Coronary artery calcifications (CAC) are shown to be a predictive factor of cardiovascular diseases. Computed tomography (CT) of the chest with a low-dose acquisition protocol is accurate in identifying CAC and provides incidental findings of these calcifications, which are commonly overlooked. This study will analyze the prevalence of incidental findings of calcification in coronary arteries in non-cardiac individuals undergoing chest CT. Methods: Consecutive cross-sectional study of an analytical and descriptive nature. Individuals of both genders who underwent chest CT by referral, over 18 years of age and without heart disease were included. Data collection was carried out using medical records and a self-applied anamnesis form. The variables referring to the CAC and the extension of the impairment were obtained from the reassessment of the chest CT images available in the institution’s system. The exams were anonymized and evaluated by two experienced radiologists. P≤0.05 was considered statistically significant. Results: 397 exams were analyzed. A prevalence of calcifications was found in 176 (44%) of the cases. The existence of these coronary calcifications is related to age (p<0.001). Calcifications are related to gender (p = 0.03) with a higher odds ratio of development in men (odds ratio [OR] = 1.55). Smoking (p<0.001), sedentary lifestyle (p<0.001), systemic arterial hypertension (p<0.001), Diabetes Mellitus (p = 0.04), and dyslipidemia (p<0.001) showed a positive association. Conclusion: The prevalence of incidental CAC findings was 44%; vary in greater numbers between mild and severe; higher odds ratio in males and increased prevalence with age. Therefore, chest CT proves to be an effective method to assess CAC, and together with the patient’s clinical history, it can be used to measure risk factors for CVD and intervene in the outcome of the condition.


Incidental Tomographic Findings of Coronary Artery Calcifications: A Prevalence Study in Southern Brazil
dyslipidemia, systemic arterial hypertension (SAH), male gender, and smoking.³Computed tomography (CT) of the chest, used with lowdose acquisition protocols, was 97.13% accurate in identifying CAC and proved to be effective in detecting or excluding them. 4This test, usually used for pulmonary diagnostic purposes, has been providing frequent incidental findings of calcifications, since there are cardiovascular conditions that can cause non-cardiac symptoms, such as dyspnea, chest pain, and hemoptysis.Thus, studies on these findings have been gaining space in the clinical and scientific scope.²6][7] Thus, the prevalence of incidentalomas and their clinical relevance have been estimated in several studies and based on different contexts. 8,9owever, there are no studies of this nature in the northwest region of the state of Rio Grande do Sul; therefore, this research aimed to fill a gap regarding population-based information on the region under study in the clinical and scientific fields.In this perspective, the objective was to analyze the prevalence

Introducton
Cardiovascular diseases (CVD) are among the main health problems in the world and, therefore, they should be prevented.¹Thus, coronary artery calcifications (CAC), initially asymptomatic, have proven to be an alarming and predictive factor for these diseases.²They are characterized by a progressive and gradual pathophysiological process, which results in abnormal vasomotor responses and/or narrowing of the vessel lumen.These changes are strongly associated with advanced age, diabetes mellitus (DM), The variables referring to calcifications of the left coronary, left anterior descending, circumflex, and right coronary arteries, as well as the extent of their impairment, were obtained from the reassessment of the chest CT images available on the Picture Archiving and Communication System (PACS) (https://www.animati.com.br/animati-workstation/) of the institution.Also in this system, the reason for the medical referral to perform the examination described in the reports was obtained.Data were compiled by a single researcher for better quality and standardization of information.

Acquisition and Interpretation of Images
The device used to perform the exams was a 32-slice Alexion CT scanner (Toshiba, Otawara, Japan) using a lowdose acquisition protocol.The examinations were performed with the patient in the supine position and in apnea.The chest images were analyzed in axial sections, in soft tissue window and only in the non-contrast phase.The exams were anonymized (Advantage Workstation, version 4.6.GE Healthcare) so that previous data did not influence the analyses and the evaluators were completely blinded regarding the patient and each other.The analyses were performed by two previously trained radiologists with more than 5 years of experience in the area.First, the images were evaluated independently by the professionals.The images that showed disagreement between physicians were reanalyzed converging on a consensual result.

Coronary calcification score by visual scale
Following the protocol performed by Shemesh et al., 10 four coronary arteries were evaluated: left main, left anterior descending, circumflex, and right.Each of them was classified and scored as absent (0), mild (1), moderate (2), or severe (3).It was characterized as mild when less than one third of the length of the entire artery was compromised, moderate when there were calcifications in one to two thirds of the artery, and severe when more than two thirds of the artery was calcified.After scoring, the results were added up, classified into: absent (0), mild (1-3), moderate (4-6), and severe (7-12).

Statistical analysis
Data collection was performed using Microsoft Office Excel 2010 and analysis using R Studio software (version 3.4.4).For the analysis of descriptive statistics, relative and absolute frequency, measures of central tendency and dispersion, were used.In the analytical statistics of the qualitative variables, the ꭓ 2 test was used to test the hypothesis of dependence between the variables as well as to verify the adherence between them, considering statistically significant p≤0.05.In the analytical statistics of the quantitative variables, the prevalence of calcification findings was estimated.To determine the number of classes for the age variable, the Sturges Rule was used.
Inter-examiner agreement was estimated using Cohen's Kappa and the reference values for analysis described by Landis and Koch. 11For the normality verification analysis, the Kolmogorov Smirnov test was used for the age variable along with the non-parametric Mann Whitney U test, considering statistically significant p≤0.05.The odds ratio was used to estimate the presence of calcification in relation to its predisposing variables.

Results
A total of 397 exams were analyzed, showing substantial inter-examiner agreement (κ = 0.77).Patients had a mean age of 61.88±16.26years, with a predominance of females (52.14%).The commonly found reasons for referral were: changes in the respiratory system (n = 94), monitoring of a pulmonary nodule (n = 47), and lung cancer (n = 27).
Sedentary lifestyle (69.02%) and family history of heart disease (44.84%) are the most worrying among the main risk factors, while cancer is the leader in relation to previous diseases, reaching 38.29% of cases, followed by SAH (46.85%), with a higher prevalence in females (Table 1).The population characterized above showed a prevalence of calcifications in 176 (44%) of the cases and it was found that the presence or absence of these coronary calcifications is related to age (p < 0.001).A greater occurrence of calcifications was observed in the age group between 76 and 84 years.However, the highest prevalence of calcification was from 92 to 100 years (100%), being more severe.Furthermore, it was possible to note that there is an increasing prevalence of calcifications above 68 years of age, reaching more than 60% of patients (Table 2).In the score used for the analysis of the arteries, seen in isolation, it was possible to verify that Calcifications are related to gender (p = 0.03) with a higher odds ratio of development in men (odds ratio [OR] = 1.55).Still on the variables that influence the development of calcifications, smoking (p < 0.001), sedentary lifestyle (p < 0.001), SAH (p < 0.001), DM (p = 0.04), and dyslipidemia (p < 0.001) showed a positive association, with SAH (OR = 3.45) and sedentary lifestyle (OR = 2.97) having the highest odds ratio (Table 3).The results of the prevalence of CAC and the degree in relation to the age groups are graphically illustrated in Figure 1. Figure 2 represents the main findings of the study.

Discussion
The present study observed a 44% prevalence of incidental findings of CAC on chest CT in patients asymptomatic for heart disease, which increases with age and with greater chances of developing in males.It can also be observed that there is a direct relationship with risk factors and associated comorbidities, both closely linked to daily living habits.Regarding the diagnostic method, its effectiveness in the clinical and scientific scope can be seen, as in previous studies.

Scopel et al. Tomographic incidentalomas of coronary calcifications
In this line of analysis of coronary arteries, studies 6,7 with predominantly male population characterization, but similar mean age to our study, found that the prevalence of CAC in asymptomatic individuals is greater than 53%.These data are in line with what was presented in this research, with a predominance of mild and severe calcifications.In the analysis of calcifications in isolation, based on the score, the right coronary artery was shown to be the most compromised, unlike other studies that point to the anterior descending coronary artery. 12,13However, this proximal compromise can cause reduction or blockage of the blood flow to a certain area of the myocardium, 14 whose outcome is one of the main causes of death. 15This prevalence in asymptomatic patients is important, because when recognized early, helps in prevention, reduces the speed of disease progression, and reduces the associated morbidity and mortality.
Therefore, there are some factors that predispose the appearance of CAC.Among them, the present study found that men are more likely to develop CAC (OR = 1.55), as observed in previous studies; 5,10 however, there are studies that point out that these findings are independent of gender. 7Another point that was proven statistically significant (p < 0.001) was the increasing prevalence with growing age.Other studies 5,7    line with these findings, which can be explained by the fact that these calcifications occur progressively, as a result of the sum of advancing age and complex biological processes, including genetics, risk factors, diseases acquired throughout life, and environmental factors. 16rthermore, the study on the prevalence of CAC in Mexico corroborates what was previously shown and demonstrates that 27% of the participants have CAC, the majority being men (40%), followed by women (13%); both genders were older and had higher values of systolic and diastolic blood pressure, glucose, and LDL cholesterol. 17In another recent study conducted in northern Brazil, a high prevalence of cardiovascular risk factors associated with coronary calcifications was observed, especially SAH (83.33%), dyslipidemia (62.22%), sedentary lifestyle (74.44%), and overweight (64.44%), being more prevalent in women, who were menopausal in the majority (90.48%). 18Based on these data, the relevance of this topic can be seen and the relationship between CAC and the variables mentioned is confirmed.
Along these lines, SAH and dyslipidemia, as described in other studies, 12,19 are statistically significant and have high odds ratios.Studies show that a sedentary lifestyle 20 and smoking 21 have substantial impacts on risk factors, as found in this study.These data are of greater importance when considering that 80% of deaths from CVD could be avoided by quitting smoking habits and practicing physical activity regularly. 22e present study is a pioneer in the Northwest region of the State of Rio Grande do Sul and has a considerably large sample number for the collection period.However, the limitations of the study include divergences between the observers who analyzed the images, which can be explained by the fact that the exam was not performed with ECG-Gated Cardiac CT (image captured in cardiac diastole), making the analysis difficult; however, they were reassessed, reaching a consensus.The study population showed a selection bias, firstly because the study was carried out in a single hospital and secondly because the individuals included were referred due to clinical indications of different pathologies.The self-applied questionnaire can be considered a weakness, as individuals may omit or not fully understand what is being asked.

Conclusion
The incidental findings of CAC in asymptomatic individuals for heart disease undergoing chest CT showed a prevalence of 44% in the interior of the Northwest of the state of Rio Grande do Sul, Brazil.These vary between mild and severe, with a higher odds ratio in males and an increase in prevalence with age.Therefore, chest CT proves to be an effective method to assess CAC, along with the patient's clinical history, and can be used to measure risk factors for CVD and intervene in the outcome of the condition.
This study is a pioneer in this region and shows the importance of future investigations, surveys and/or evaluations of patients with CVD.
Scopel et al.Tomographic incidentalomas of coronary calcificationsthe most compromised artery was the right coronary, in 193 (48.61%) of the cases.

Figure 1 -
Figure 1 -Graphical representation of the prevalence of CAC and the degree of involvement in relation to age.

Scopel et al. Tomographic incidentalomas of coronary calcifications of
incidental findings of calcification in coronary arteries in non-cardiac patients undergoing chest CT.

Participants
This is a cross-sectional study of analytical and descriptive nature, developed in based on the Guidelines and Regulatory Norms for Research Involving Human Beings, in accordance with the Resolution of the National Health Council (Conselho Nacional de Saúde -CNS) No. 466/12 and approved by the Research Ethics Committee of UNIJUÍ (CAAE: 84431118.2.0000.5350).Individuals of both genders who underwent chest CT by referral were included.Individuals under 18 years of age, exams performed by referral from a cardiac physician, exams with technical difficulties for image evaluation and duplicate exams, that is, two or more exams performed by the same patient within an interval of less than 6 months, were excluded.

Table 1 -Description of predisposing factors for the formation of arterial calcifications
SD: standard deviation; SAH: Systemic Arterial Hypertension; DM: Diabetes Mellitus.

Table 3 -Relation of predisposing factors with coronary calcifications and the odds ratio of occurrence
present data in