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Prevalence of suggestive images of carotid artery calcifications on panoramic radiographs and its relationship with predisposing factors

Panoramic radiographs (PR) can display radiopaque images suggestive of calcified atheroma in the carotid artery in asymptomatic patients. The aim of this study was to evaluate the prevalence of these images on PR and their linkage with hypertension, obesity, age, gender and smoking habits. PR of 505 patients were evaluated. They were older than 30 years old and their PR had been taken for different clinical reasons. Their body mass index was calculated; their waist circumference was also taken into consideration. Information about smoking habits and hypertension was obtained. The observers analyzed the presence of radiopaque mass in the region of the cervical vertebrae C3-C4 through the PR, confirmed by an antero-posterior (AP) radiograph. The results showed a 7.92% prevalence of suggestive images of calcifications on PR and on AP radiograph. The adjusted Odds Ratio showed association with age and smoking habits. The calcification process is almost nine times higher for the elderly when compared to the young. As far as smokers are concerned, this process is twice worse when compared to no smokers. In conclusion, 7.92% of the group studied presented suggestive images of carotid atherosclerosis on PR, which is directly associated with the age and smoking habits.


Introduction
Cardiovascular diseases continue to be the main cause of morbidity and mortality worldwide. Cerebrovascular accidents are responsible for killing or disabling more than half a million Americans every year 1 . In Brazil, about 68,000 deaths per year are reported to be caused by stroke. This disease is the leading cause of death and disability in the country, generating significant economic and social impact 2 . People over 55 are at a great risk of having a stroke. This risk increases as they get older 3 .
Some studies have linked the presence of the carotid artery calcifications to systemic diseases such as obesity (body mass index and waist circumference), hypercholesterolaemia, hypertension, diabetes, renal stones, dental infections, prior atherosclerosis and with increasing age 4-12 .
Panoramic radiograph is one of the most requested complementary exam by dentists. Along with the evaluation of dental and maxillofacial hard tissues, panoramic radiograph can be used to spot soft tissue calcifications including calcified carotid artery atheroma 13 . The presence of calcified carotid artery plaque on panoramic images is an indicator of the risk of future adverse cardiovascular events 5 . Studies show that the prevalence of theses calcifications on panoramic radiographs taken for oral health reasons in the general dental outpatient groups, ranges from 2% to 5% 14 . It is important to highlight that calcifications may not imply significant stenosis and not all atherosclerotic lesions are calcified. Despite that, the calcifications present on dental radiographs could be quite often associated with significant carotid diseases. This finding can be considered a cost-effective incentive for the use of Doppler sonography 13 .
When dentists are suspicious about the presence of carotid artery atheromas in panoramic radiographs, they play an important role for their patients' lives, as they guide and immediately refer their patients to doctors for adequate medical treatment 15 .
In recent years, a number of publications have detected calcifications on panoramic radiographs 5,[7][8][9][10][11][12][16][17][18] . Although the diagnosis by panoramic radiography is reported, when it comes to the Brazilian population, no studies have analyzed the calcification prevalence and its association with risk factors.
The purpose of the present study is, therefore, to determine the prevalence of radiopacities suggestive of calcified atherosclerotic plaques on carotid artery on panoramic radiographs. Their association with hypertension, obesity, age, gender, smoking habits and history of cardiovascular diseases will also be studied.

Methods
The study was approved by the local ethics committee. Besides, formal consent was given by each subject. 505 patients agreed to take part in the research, all of them over their thirties (199 males and 306 females). The average of age being 50.1 years old. All patients were attended at the Department of Oral and Maxillofacial Radiology, Piracicaba Dental Scholl, during the years 2013-2014. PR were taken for different purposes regardless of this study.
Information about the lifestyle, such as smoking habits and medical history (hypertension, own cardiovascular disease or family history of cardiovascular disease, stroke or medication use) of each patient was assessed through a standardized questionnaire applied by a trained observer. Weight was measured to the nearest 0.1 kg while the subjects were dressed in light clothing. Height was measured to the nearest 0.1 cm with the subject in stocking feet.
Body mass index (BMI, kg/m 2 ) was calculated by dividing the body weight (kg) by square of height (m 2 ), according to OMS, 2009 19 : 1 -Malnourished: < 18.5; 2 -Normal: 18.6 -24.9; 3 -Overweigth: 25.0 -29.9; 4 -Obesity: > 30.0 Abdominal circumference was measured with the subject standing, at the midway between the lower rib margin and the iliac crest. The abdominal circumference was classified according to OMS, 2009 19 : Female: 1 -Ideal: ≤ 80.0 2 -Increased: 80.0 -93.9 3 -Substantial: ≥ 94.0 Blood pressure was measured after at least 5 min of rest in the sitting position using a mercury sphygmomanometer. Notwithstanding the individuals who reported a state of hypertension previously diagnosed by a doctor and who were under medication to control blood pressure, were directly considered hypertensive.
Two oral and maxillofacial radiologists interpreted all the panoramic radiographs. The presence of carotid artery calcifications appeared as heterogeneous radiopacities in a verticolinear orientation adjacent to the hyoid bone, epiglottis and cervical vertebrae either at, above or below the intervertebral space between C3 and C4. Each observer interpreted each panoramic radiograph individually, this followed a discussion of each image between the two observers. If the two observers agreed, a positive diagnosis was made.
The patients whose cases were defined as positive by the two examiners ( Figure 1) were asked to undergo a modified anterior-posterior (AP) radiograph (with chin elevated) ( Figure 2) in order to confirm or refute the suggested findings on the panoramic radiograph. If the AP confirmed the calcification, the individual was referred to the cardiologist evaluation and if possible to realize carotid Doppler ultrasound.
The data analysis was performed by SAS (9.1.3 version; SAS Institute Inc., Cary, NC, USA). The crude logistic regression was performed to analyze the association between presence and laterality of calcification and different factors studied (gender, age, BMI, abdominal circumference, hypertension, smoking and own or family medical history of cardiovascular diseases). Variables with p < 0.05 in the crude analysis were selected for initial inclusion in the multivariate logistic regression to determine the independent predictors of the presence of calcification.

Results
The prevalence of suggestive images of calcifications on PR, confirmed by AP radiograph, was 7.92% in the total of individuals; of these, 32.5% were male and 67.5% were female. In the male population, there was a 6.53% prevalence, while in the female group it was 8.82%.
The presence of calcifications according to the predisposing factors studied is presented in Table 1. Subjects with calcifications were older and had a higher BMI and abdominal circumference. They also were hypertensive, had a history of cardiovascular disease and smoking habits. However, BMI, abdominal circumference and history of cardiovascular disease were not significantly associated with calcifications (p > 0.05). The brute regression showed that the presence of calcification was associated with age, hypertension and smoking habits. Table 2 shows the distribution of uni and bilateral cases of calcifications detected on PR and the factors studied; there was no correlation between the factors and laterality.  When these same parameters were adjusted, the strength of the association was attenuated for hypertension, but remained statistically significant for age and smoking habits (Table 3). Concerning to age, it was observed that the risk for older people increases up to almost nine times when compared to young. For smokers, the risk is twice when compared with no smokers.

Discussion
Atherosclerotic tend to accumulate, in form of irregular plaques, within the bifurcation of the common, external, and internal carotid arteries. However, not all atherosclerotic lesions are calcified; furthermore, the presence of calcification in this location is not a definitive indicator of vascular disease 14 . Because of its anatomical position, this region can be viewed on panoramic radiographs, which is a radiographic modality com-monly requested in dentistry. As atherosclerosis may be an asymptomatic condition, it may be an incidental finding on routine panoramic examination of the patient.
As other calcifications can appear in the same region of atheroma on panoramic radiograph, which may be anatomic (hyoid bone, cartilage triticeous, epiglottis, etc.) or pathologic (calcified lymph nodes, tonsilloliths, phleboliths, etc.) 3 , it is necessary another radiographic (AP) or exam for the diagnosis to be confirmed.
The gold standard for the detection of atheroma is ultrasonography with Doppler; the panoramic radiograph cannot be considered an accurate test for stenosis, but a finding on radiography requires referral to a specialist for diagnosis, because there is a connection between findings in panoramic radiography and cardiovascular events 16 . Thus, the panoramic radiograph may be a risk marker for subsequent cardiovascular events 12 ; moreover, previous studies have found a correlation between calcifications found in the panoramic radiograph with the findings on ultrasonography 6,13,15,20,21 and others also used the panoramic radiograph to evaluate the prevalence of atheroma 4,16 .
In this study, the differential diagnosis were made by the AP radiograph, a method also used by Henriques et al. 22 and Almog et al. 3 . This aimed the diagnosis, because radiopacities suggestive of calcified atherosclerotic plaques on carotid artery is displayed laterally to the vertebra, while the images of other structures of average body region, as calcification in the triticeous cartilage, which is the greatest cause of erroneous diagnosis of atheroma 23 , are overlapping to the spine. This was the method available in the Radiology Clinic where the study was conducted; so the patient could not perform an ultrasound of the neck immediately for confirmation of the presence of atheroma and, when the radiopaque image had been viewed, the patient was referred to an appropriate doctor.
The population studied was in their thirties. In younger patients, only a minor number of cases with carotid calcifications can be found 16 . Despite this, the accumulation of calcium in the aorta starts to occur after the person is twenty years old. That is why it was decided to include younger patients, so almost all age groups with possibility of having calcification in the carotid artery could be analyzed.
The results of this study demonstrate that 7.92% of the subjects showed a calcified carotid artery atheroma, which was confirmed by AP radiograph. Previous studies have found a prevalence of carotid calcification on panoramic radiographs close to this study's results, ranging from 5.6% to 6.8% 9,15,18 , while other studies obtained lower values of 1.6% to 4.8% 8,13,16,17,24 . However, in some specific conditions, such as patients with primary hyperparathyroidism, kidney stones and cardiovascular disease symptoms, the prevalence was higher 4,8,18 .  Gender, age, obesity, waist circumference, hypertension, previous history of cardiovascular disease and patient's family history and smoking habits were the risk factors studied, but only the association between calcification, age and smoking habits were significant. Other studies had also showed a correlation with age 13,18,25 . In fact, in a Turkey population, in addition to the age, it was found correlation with gender (male), family history of cardiovascular disease and dyslipidemia; moreover, there was no correlation with hypertension and smoking habits 24 . These discrepancies in the predictors factors could be attributed to differences in the populations' studies. Indeed, the authors analyzed symptomatic patients of a Cardiologic department whereas this study analyzed asymptomatic patients who were referred to a panoramic radiograph for dental treatment, representatives of as small portion of the Brazilian population (very heterogeneous), in the city of Piracicaba/SP with a medium income and without specific diseases. When the relationship was studied according to specific conditions, such as in patients with primary hyperparathyroidism, despite the prevalence being of 40%, there was no correlation with atherogenic pattern (age, body mass index, hypertension, diabetes, hyper-lipidemia) 3 . Postmenopausal Women over 50 years old, for its part, showed 11% of prevalence of carotid calcification, also not correlated with hypertension, past history of myocardial infarction and hypercholesterolemia 10 .
It is crucial for the dental practitioners to know the characteristics and prevalence of carotid artery calcifications to perform a thorough evaluation of areas of panoramic radiograph, which can identify such calcifications. Furthermore, the professionals should differentiate these calcifications from the others when it is possible to perform an AP radiography 26 . Consequently, when their presence is suspected or confirmed, the patient has to be informed of the findings and its implications. He has also to be referred to a medical evaluation. To this end, patients with smoking history require special attention.

Conclusions
The study came to the conclusion that, among the factors studied, only the age and smoking habits were correlated to the presence of suggestive images of atheroma in PR. Besides, this prevalence was of 7.92% of all the individuals assessed.

Collaborations
ACR Brito, HAR Nascimento, R Argento, T Beline, GMB Ambrosano, DQ Freitas all participated in the preparation and performance of the tests, the analysis of results and the composition of the article for publication.