Presence of carotid artery calcification on panoramic radiographs of patients with chronic diseases
By Farah Masood, BDS, MS
Robert C. Wild, MS, MPH
Jennifer Jenkins, DDS
Lida Radfar, DDS, MS
Featured in General Dentistry, January/February 2009
Pg. 39-44

Posted on Wednesday, January 07, 2009

This study sought to investigate carotid artery calcification (CAC) on panoramic radiographs from both healthy patients and those patients suffering from different chronic diseases. A total of 247 patients met the inclusion criteria and were reviewed. Ninety-two patients had one or more chronic diseases as indicated by their records; the remaining 155 patients had no mention of a chronic disease and were considered to be healthy controls. Among all patients, 13% had evidence of CAC, 21% of the patients with one or more chronic diseases had CAC, and only 8% of the patients in the control group had CAC. Those with liver disease only had the highest proportion (33%) of CAC.

Received: February 1, 2008

Accepted: April 8, 2008

The 20th century saw significant changes in the profile of diseases and health in the United States. More than 90 million Americans live with chronic illnesses, including the most prevalent and most preventable, such as cardiovascular diseases, cancer, and diabetes. Chronic diseases account for one-third of the potential life lost before age 65 and for 70% of all deaths (1.7 million each year) in the United States.¹

Cardiovascular diseases (mainly heart disease) are the leading cause of death in the U.S., while strokes are the leading cause of disability and the third leading cause of death.^1,2 Extracranial carotid artery stenosis accounts for approximately two-thirds of ischemic strokes.³ An increased common carotid intima media thickness is associated with future cerebrovascular and cardiovascular events.³ Smoking, obesity and hypercholesterolemia, uncontrolled diabetes, uncontrolled hypertension, renal disease, and autoimmune rheumatic diseases are common risk factors for carotid artery disease.^4-9

At least 50 million U.S. adults have serum cholesterol levels high enough to require medical attention and treatment, putting this group at high risk for heart disease and stroke.¹⁰ According to the American Diabetes Association, approximately 12 million overweight individuals in the U.S. (aged 45–74) are at an increased risk for diabetes.¹¹ Diabetic patients have accelerated atherosclerotic vascular lesions that put them at increased risk for coronary, cerebral, and peripheral arterial diseases.¹² Hypertension increases the chance of developing heart disease, a stroke, or other serious conditions. According to the CDC, high blood pressure is easily detectable and usually can be controlled.¹³

More than four million Americans are afflicted with liver disease and suffer from liver dysfunctions such as hepatitis, cirrhosis, or fatty liver disease.^14,15 Nonalcoholic fatty liver disease results in a characteristic metabolic disorder and is associated with carotid atherosclerosis. Studies show that patients with non-alcoholic fatty liver disease have a greater prevalence of carotid atherosclerosis than controls.¹⁶ Based on the literature, acute hepatic failures result in increased cardiac output, decreased systemic vessel resistance, and a significant decrease in carotid blood flow.¹⁷

The National Center for Chronic Disease Prevention and Health Promotion is encouraging a national effort to prevent these chronic diseases. Screening patients to identify more cases is an effective prevention strategy.¹

Recent research has described the use of panoramic radiographs as a diagnostic tool for observing calcification of the carotid arteries.^18,19 A majority of cerebrovascular accidents are caused by calcification in the region of the carotid artery bifurcation.¹⁸ These calcifications can be detected with panoramic radiographs.¹⁹ Panoramic radiographs of patients with other systemic diseases (such as diabetes mellitus and renal disease) have been reviewed and significant findings of carotid calcifications have been reported.^8,20,21

At present, very little published data are available concerning examining panoramic radiographs for the prevalence of carotid artery calcification (CAC) in patients diagnosed with chronic diseases. This study investigated the prevalence of CAC on panoramic radiographs in healthy patients compared to patients suffering from different chronic diseases.

Materials and methods

This study utilized the dental records of 500 consecutive patients who came to the University of Oklahoma College of Dentistry between October 2003 and June 2005 for routine dental care. The study was approved by the Institutional Review Board at the University of Oklahoma. Charts were identified by a computer system based on the patients’ age range. Patients age 40 and older who had completed the school’s standardized medical questionnaire and had a diagnostically acceptable panoramic radiograph in the records were included in the study.

The patients’ charts were reviewed for demographic data and the presence or absence of systemic diseases, including liver disease, diabetes, hypertension, angina or myocardial infarction (MI), and transient ischemic attack (TIA) or stroke; patients who had any other systemic diseases were excluded from the study. Patients with no systemic disease were used as the control population.

Patients with chronic disease were further classified as having diabetes only, hypertension only, liver disease only, or two or more chronic diseases (history of TIA or stroke, liver disease, diabetes, hypertension, or angina or myocardial infarction), resulting in a total of five groups including controls.

Panoramic radiographs were evaluated for the presence or absence of CAC. Selection criteria for panoramic radiographs included correct patient positioning (anterior teeth not showing excessive horizontal or vertical magnification, equal ramus width bilaterally, no superimposition of the cervical spine over the ramus) and radiographs that showed diagnostically acceptable density and contrast (with no under- or overexposure). Panoramic radiographs of all patients were taken when the patients were seen for routine dental care. The units were operated at a range of 6–10 mA; the peak kilovoltage ranged from 63–81, depending on the size of the patient’s jaw. At that time, the exposed radiographs were processed according to the manufacturer’s directions using an automatic processor (Konica QX-70; Konica Minolta, Ewing, NJ; 800.934.9034).

Following patient selection, two examiners and co-authors evaluated the panoramic radiographs. One of the examiners (FM) was a board-certified oral and maxillofacial radiologist with more than eight years of experience in panoramic interpretation; the other examiner (JJ) was a third-year dental student with limited experience in the area. Both examiners were trained and calibrated in diagnosing CAC, based on criteria found in scientific articles that had been published in peer-reviewed journals.²² The examiners’ training included studying the literature and an American Academy of Oral and Maxillofacial Radiology (AAOMR)-sponsored video to learn the descriptions of anatomical structures in the region of the cervical vertebrae and how to find evidence of CAC on panoramic radiographs.^23,24 Various panoramic images were studied from previously mentioned items for calibration purposes. The training session utilized approximately 100 panoramic films that were not part of the study.²⁰

CAC can be visualized on panoramic radiographs as single or multiple discrete radiopaque/high density nodular masses within the soft tissue of the neck. Carter et al reported that calcifications at the carotid bifurcation have a distinct radiographic appearance and location that distinguishes CAC from other radiopacities in the same region (including those seen on the hyoid bone, epiglottis, ear lobe, styloid process, and calcified stylo-hyoid ligament).²⁵ In keeping with previously published studies, the present study reported only single or multiple radiopacities within the soft tissue of the neck, 1.5 cm inferior and 2.5 cm posterior to the cortical rim of the mandibular midpoint angle.²⁰

All study images were examined under subdued ambient lighting conditions through the use of a transmitted light from a standard view box (Luminator, Dux Dental, Oxnard, CA; 800.833.8267) and a concentrated light source (Wolf X-ray Corporation, Deer Park, NY; 800.356.9729). For questionable cases, a magnification glass was used as needed. When both examiners agreed on the radiographic findings, the images were included in the study.

Statistical analysis

SAS/STAT software 9.1.3 (SAS Institute Inc., Cary, NC; 800.727. 0025) was used to describe the relationship between the exposure (type of disease present versus no disease present) and outcome (presence or absence of CAC), adjusting for age and gender. Logistic regression was employed to calculate adjusted odds ratios. Profile likelihood confidence intervals were reported with the estimated adjusted odds ratios. First, the proportion of patients with CAC and any type of chronic disease were compared to the proportion of healthy controls with CAC. The presence of interaction and confounding factors between disease classification, gender, and age information was tested. The model fit was assessed using the Hosmer and Lemeshow Goodness of Fit (HL-GOF) Chi-Square test. All statistical tests were performed using a significance level of 0.05.

Results

A total of 247 patients met the study criteria; this population had a mean age of 50.45 (SD = 4.82) with a female-to-male ratio of 128:119. Of the 247 patients, 155 did not disclose any chronic diseases and met the inclusion criteria for healthy controls; the remaining 92 had at least one chronic disease. The division of the chronic disease group resulted in 10 patients with diabetes only, 36 with hypertension only, 15 with liver disease only, and 31 with two or more of these chronic diseases (see Table 1).

Of the 247 panoramic radiographs reviewed, 32 (13%) revealed CAC (Fig. 1); more than 50% of these CAC cases were unilateral calcifications. The association between exposure levels (healthy controls versus patients with chronic disease) and outcome (that is, the presence or absence of CAC) did not differ by gender (Wald χ², p = 0.509) or age (Wald χ², p = 0.9871). A comparison of the unadjusted odds ratios with the gender- and age-adjusted odds ratios revealed no evidence of confounding. The odds of an individual with CAC in the chronic disease group were 2.88 times greater (95% PL CI: 1.33, 6.41, p = 0.0080) than the odds of CAC in the control group, after adjusting for gender and age. The HL-GOF test indicated an appropriate fit of the model to the data (p = 0.494).

Sample sizes in the stroke or TIA-only, MI-only, and diabetes-only groups were too small to test for an association with CAC; as a result, these individuals were left out of the analysis and associations with the groups of patients with hypertension only, liver disease only, and those with two or more chronic diseases. The association between exposure level (healthy control versus type of chronic disease) and outcome (presence or absence of CAC) did not differ by gender (Wald χ², p = 0.426) or age (Wald χ², p = 0.985). Once again, confounding was assessed by comparing unadjusted odds ratios in each category with age- and gender-adjusted odds ratios. There was no evidence to suggest that confounding existed for either age or gender.

A statistically significant relationship existed among those individuals with liver disease only and those with two or more chronic diseases. The hypertension-only group did not show a statistically significant association. Table 2 presents the age- and gender-adjusted odds ratios, with their corresponding profile likelihood-based confidence intervals. The fit of the final model was assessed (using the HL-GOF test) and showed appropriate fit (p = 0.730).

Discussion

This clinical study is the first to report on the relationship between liver disease (reported by patient charts as hepatitis) and CAC. The authors have found no previous report in the English literature regarding an association between the two conditions. Acute hepatic failure has been found to decrease systemic vessel resistance and lead to a significant decrease in carotid blood flow.¹⁷ Non-alcoholic fatty liver disease was found to be an independent factor for increased intima media thickness and advanced carotid atherosclerosing. The hepatic injury in non-alcoholic fatty liver disease was considered to be a possible mechanism for increasing abnormal lipoprotein metabolism and development of cardiovascular problems.¹⁶

CAC is responsible for the majority of cerebrovascular accidents.²⁶ The lesions of atherosclerosis occur principally in large- and medium-sized elastic and muscular arteries and can lead to ischemia of the heart, brain, or extremities, resulting in infarction.²⁶ The process of atherogenesis has been considered to consist largely of lipids accumulating within the artery wall; however, the new concept depicts atherosclerosis as an inflammatory disease that involves a series of highly specific molecular and cellular reactions, leading to endothelial dysfunction.²⁷

The endothelial dysfunction may result from elevated and modified low density lipid (LDL) cholesterol, free radicals (caused by cigarette smoking), hypertension, diabetes mellitus, genetic alterations, infectious microorganisms (such as herpes viruses), or a combination of these factors.²⁷ The compensatory responses of the endothelial dysfunction include an up-regulation of the cell adhesion molecules and the endothelium’s increased adhesion to leukocytes or platelets. The inflammatory response stimulates migration and proliferation of smooth-muscle cells to form an intermediate lesion that can thicken the artery wall.²⁸ This response is mediated primarily by monocyte-derived macrophages and T lymphocytes.²⁹ Activation of these cells leads to the release of hydrolytic enzymes, cytokines, chemokines, and growth factors, which cause additional damage and lead to focal necrosis (which is covered by a fibrous tissue).^30-32

As a lesion expands in size, the artery cannot compensate by dilation. The lesion intrudes into the lumen and alters the blood flow. A 2004 report by Kitamura et al investigated 1,289 elderly Japanese men and reported that an increased intima media thickness of the common carotid artery and an uncalcified plaque in the internal carotid artery were risk factors for stroke among this population.³³

CT scans, ultrasound, and angiography are methods for diagnosing plaque and calcification of the carotid artery.^34-36 Calcification in plaque indicates a chronic disease pattern; however, the absence of calcification on radiographs of the neck or lateral aspect of the skull does not exclude the possibility of significant extracranial carotid disease. High-grade stenosis of the proximal carotid artery may occur in the absence of calcifications and dense carotid calcification may be seen in the absence of a high-grade carotid stenosis.³⁴

Early detection of CAC may help to identify patients at risk for severe cardiovascular problems. Panoramic radiographs are not a complete screening tool for these calcifications but it is suggested that all panoramic radiographs should be examined carefully for evidence of CAC. Radiographs may reveal a number of other calcified bodies in the same region of the neck. Differential diagnosis of these radiopacities that can be misdiagnosed as CAC include phelebolith, tonsillolith, sialolith, calcification of the lymph nodes and other soft tissue calcifications, and triticeous cartilage.³⁷ Based on the previously published criteria related to the location and the radiographic appearance of the calcifications, the lesions can be identified and referred for further evaluation.²⁵

The small sample size of the present study supports previous studies by stating that CAC can be observed on panoramic radiographs and that patients with chronic diseases have a higher calcification rate. More clinical studies with a larger sample size are necessary to determine the relationship between CAC and hepatitis. This study can motivate dentists to play a more active role in their patients’ medical well-being. Most people do not realize that their arteries are blocked until they experience a cerebral accident or cardiac attack. It is important to identify patients who are at risk for strokes.

Although the sample size of this study is small, the results indicate that dentists should review patient panoramic radiographs for the presence of calcification, especially for patients with chronic systemic diseases. If CAC is detected, the patient should be referred to his or her physician for a follow-up. The authors recommend further clinical studies to assess the relationship between CAC and liver disease.

Conclusion

Undetected carotid artery stenosis due to calcification may result in stroke without warning. A detailed evaluation of the panoramic radiograph is very important. Taking panoramic radiographs solely to detect CAC is not recommended but patients should be referred for further evaluation when a radiograph is available and calcification is detected. More research is needed to further study the relationship between CAC and stroke in such patients.

Acknowledgements

This study was supported by the Dean Robert Society, College of Dentistry, University of Oklahoma Health Science Center.

Author information

Dr. Masood is an associate professor, Department of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Science Center in Oklahoma City, where Dr. Radfar is an associate professor and Mr. Wild is a research assistant, Bioinformatics and Data Management Center. Dr. Jenkins is in private practice in Edmond, OK.

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