Objectives: The detection of carotid artery calcification at an early stage is important to reduce the effects of cardiovascular disease in patients undergoing hemodialysis. This study sought to evaluate the prevalence of carotid artery calcification from panoramic radiographs of patients who were undergoing hemodialysis and to assess the relationship between such calcification and certain medical and periodontal parameters.
Materials and Methods: We evaluated 120 panoramic radiographs from patients who were undergoing hemodialysis for the presence of carotid artery calcification. Full-mouth periodontal clinical and medical parameters were recorded, and patients were diagnosed on the basis of the new periodontal disease classification. Patient medical records from the same period (the same week) during which the panoramic radiographs were taken were also assessed.
Results: Among the 120 participating patients, panoramic radiographs from 27 patients (22.5%) showed a uni- or bilaterally radiopaque mass. Of the periodontal clinical parameters investigated for associations between patients with and without carotid artery calcification, there was only a significant difference shown for probing pocket depth (P = .017). No significant differences were found between the groups with and without carotid artery calcification with regard to any other medical or periodontal parameter.
Conclusions: In our study group, suspected carotid artery calcifications were detected on panoramic radiographs in about one-fourth of total patients receiving hemodialysis. Because of the significant relationship found between probing pocket depth and carotid artery calcification, the presence of periodontal disease may be associated with calcifications in these patients. Dentists should maintain awareness in detecting these lesions when evaluating panoramic radiographs of patients undergoing hemodialysis.
Key words : Carotid calcification, Periodontal disease, Systemic diseases
Hemodialysis, which is necessary for patients whose kidneys have decreased functional capacity, is the most common form of renal replacement therapy, and it is known to improve the long-term survival of patients with end-stage kidney disease.1,2 Patients who are placed on hemodialysis as a result of chronic renal failure are known to be at an increased risk of developing atherosclerotic complications.3 Vascular calcification in adult patients who are undergoing long-term hemodialysis is associated with increased stiffness of the carotid artery and aorta, which are both large, capacitive, elastic-type arteries. This may lead to increased cardiovascular morbidity and mortality in such patients.4 Atherosclerosis is an important risk factor for cardiovascular diseases in these patients; therefore, early detection of calcifications could provide life-saving information.5,6
The atherosclerotic changes that occur in the carotid artery, which stem from the increased thickness of the carotid intima-media, are associated with the presence of both cardiovascular disease and stroke in the general population.7 The related microbial pathogens (or their products) cause the recruitment of periodontal disease into the bloodstream and thus incite both local and systemic inflammatory responses.
Periodontitis is a bacterially driven chronic and multifactorial inflammatory disease that is characterized by the progressive destruction of the tooth-supporting tissues, which can lead to tooth loss.8 Although periodontal disease frequently occurs as a consequence of plaque deposition, periodontitis can be modified by environmental factors, smoking, hormones, diabetes, drugs, and certain systemic diseases.9,10 Previous studies have suggested that periodontal disease causes a source of systemic inflammatory load; on the basis of this, it has a positive relationship with various systemic diseases, including adverse events during pregnancy,11 cardiovascular disease,12 rheumatoid arthrosis, diabetes mellitus (DM),13 and chronic kidney disease (CKD).14
As a chronic infection, periodontitis results in a cumulative chronic inflammatory burden through the systemic dissemination of inflammatory mediators produced by the tooth supporting the tissue’s destructive immune-inflammatory response.2 This is hypothesized to cause endothelial damage and to promote atheroma formation, maturation, and exacerbation.15-17 Periodontal pathogens and their products (eg, lipopolysaccharides), which are responsible for inducing the systemic antibody response and higher levels of C-reactive protein, are common risk factors for CKD and have a fundamental proceeding role in atherosclerosis that contributes to cardiovascular disease.18,19
On panoramic radiographs, carotid artery calcification (CAC) presents as unique or multiple calcified points that are less dense than adjacent calcified structures.20 The CAC-related findings from panoramic radiographs can be characterized as one or more radiopacities close to the cervical vertebrae, either above or below the intervertebral space between the C3 and C4, 2 to 4 cm below the angle of the mandible. Therefore, panoramic radiographs, which are routinely used in dental practice for diagnosis of periodontal and dental diseases, could also serve as a noninvasive, inexpensive, and easily repeatable method for the detection of CAC.21
The present study aimed to detect the presence of CAC on dental panoramic radiographs from CKD patients who were undergoing hemodialysis. The study also investigated the association between CAC and the patients’ medical and periodontal parameters.
Materials and Methods
Ethics and consent
All study procedures were performed in accordance with the Declaration of Helsinki and the Research Committee Regulations, and approval for the study was obtained from the Research Ethics Committee of Baskent University (D-KA 18/34).
Patients and periodontal parameters
Our cross-sectional study included 120 patients on hemodialysis who were referred from the Department of Nephrology of Baskent University between 2019 and 2020. Patients underwent 3-hour to 4-hour hemodialysis session 3 times weekly using a high-performance dialyzer at a blood flow rate of 250 to 300 mL/min and a standardized dialysis flow rate of 500 mL/min. A bicarbonate-containing dialysis solution was used during hemodialysis. The study’s purpose and protocol were explained to the patients, and written informed consent was obtained from all patients.
Full-mouth periodontal parameters of patients were examined by 1 periodontist at 6 locations per tooth (mesial-buccal, mid-buccal, distal-buccal, mesial lingual, mid-lingual, and distal-lingual), with the exception of the third molars. The probing depth, clinical attachment level, bleeding on probing (%),22 and plaque index23 were recorded using a periodontal probe (Hu-Friedy). On the basis of the clinical and radiographic data, each patient’s periodontal status was determined in accordance with the periodontal disease classification recently published by the European Federation of Periodontology and the American Academy of Periodontology.24 Gingivitis on an intact periodontium was defined as ≥10% bleeding sites, a probing depth ≤3 mm, no probing attachment loss, and radiographic signs of alveolar bone loss due to periodontal disease. Moreover, gingivitis with a reduced periodontium was defined as ≥10% bleeding sites, a probing depth <4 mm, probing attachment loss, and possible radiographic signs of alveolar bone loss.25 Periodontitis was determined on the basis of clinical attachment level, radiographically assessed alveolar bone loss, a probing depth ≥4 mm, and ≥10% gingival bleeding sites. The stage and grade of the periodontitis was determined based on the consensus report published by Papapanou and colleagues.26
Radiographic evaluation and medical parameters
All digital panoramic images were acquired using the same machine (Veraviewpocs 2D, Morita),
with the following exposure parameters: 64 to 66 kVp, 6 to 9 mA, and 10 seconds. Two observers with 10 years of experience at the Department of Dentomaxillofacial Radiology of our university evaluated the images on 2 different dates and 15 days apart by using the ClearCanvas (Synaptive Medical) program on an LED monitor under low light (HP Prodisplay P221 21.5-inch LED Backlit LED monitor, HP Inc). Suspected CAC findings were defined as one or more radiopaque mass adjacent to the cervical vertebrae at or below the intervertebral space between C3 and C4 on the panoramic radiographs (Figure 1 and Figure 2). The CACs were scored as present or absent by 2 dentomaxillofacial radiologists. Panoramic radiographs with unclear visualization because of movements of patients during the exposure or those that did not include C3 and C4 vertebrae regions were eliminated.
Medical parameters were obtained from patient medical records simultaneously with the panoramic radiography (on the same week). Parameters included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein, glomerular filtration rate, C-reactive protein, triglyceride, potassium, calcium, hemoglobulin, albumin, phosphorus, parathyroid hormone, creatinine, and blood urea nitrogen.
Statistical analyses of the data obtained in our study were conducted with the SPSS software program. The normal distribution of the data was tested with the Shapiro-Wilk test. Comparisons of age, dialysis year, number of teeth, plaque index, bleeding on probing, probing depth, clinical attachment level, and whole blood parameters between the groups with and without CAC were carried out with independent t tests for normally distributed data and Mann-Whitney U test for nonnormally distributed data. Relationships between CAC and smoking, hypertension, DM, and diagnoses were determined using chi-square test or Fisher exact test according to the number of data in cross-tab cells. Binary logistic regression analysis was used to determine the risk factors for the presence of CAC. The odds ratios and their 95% CIs were also calculated for each parameter found to be statistically significant in the logistic regression analysis. Statistical significance level was accepted as P < .05.
A total of 120 patients (55 females, 65 males) who were treated with hemodialysis at our center were included in this study. The mean age of all participants was 62.64 ± 15.69 years (range, 22-93 years). The mean duration of hemodialysis was 6.14 ± 5.63 years. Of the 27 patients with radiographic CAC, 9 were bilateral (7.5%) and 18 were unilateral (15%). Table 1 presents the descriptive statistics, including mean and odds ratio values, for the demographic variables for groups with and without CAC. Retrospective Doppler ultrasonography examinations of patients with suspected CAC, as seen on panoramic radiographs, could only be evaluated for 17 patients. Doppler ultrasonography examinations confirmed the presence of CAC in 15 of 17 patients on hemodialysis. With regard to current echocardiographic findings, data for only 20 of 27 patients with radiographic CAC were available. Presence of left ventricular concentric hypertrophy was detected in echocardiographies in 18 of these patients (67%). Twenty patients (74%) with radiographic CAC had a history of coronary artery disease. When we compared groups with and without CAC, we observed no significant differences with respect to smoking status (P = .165), hypertension (P = .368), and DM (P = .105). In addition, no statistically significant differences were shown with regard to mean age (P = 1.000) and duration of hemodialysis (P = .924) between the groups with and without CAC (Table 1). Patients in the group without CAC had a greater number of teeth than patients with CAC; however, this difference was not statistically significant (P = .548).
Ten patients on hemodialysis (8.3%) were diagnosed with gingivitis, 40 patients (33.3%) were diagnosed with reduced periodontium with gingivitis, and 7 patients (5.8%) had stage I and II periodontitis. Thirty-four patients (28.3%) were diagnosed with stage III and IV periodontitis, with similar distribution of periodontal diagnosis between groups with and without CAC (P = .473). The incidence of stage III and IV periodontitis was almost 38% in patients with CAC and 37% in those without CAC.
As shown in Table 2, the periodontal parameters of groups with and without CAC were not statistically different except for probing depth. Median probing depth values were significantly higher in those with CAC (3.06 mm [range, 2.46-4.50 mm]) than in those without CAC (2.74 mm [range, 1.75-5.37 mm]) (Table 2).
We observed no statistically significant differences in medical parameters between patients with and without CAC. Nevertheless, mean triglyceride values tended to be higher in those with CAC compared with those without CAC (P = .089; Table 3).
Multivariate logistic regression analyses showed that duration of hemodialysis was significantly associated with the presence of CAC (P = .047). Duration of hemodialysis was associated with 1.1 times (95% CI, 1.001 to 1.161) likelihood of presence CAC in patients on hemodialysis.
Smoking, alcohol, stress, obesity, genetic factors, sex, age, low physical activity, and systemic diseases such as hypertension, DM, and hypercholesterolemia are risk factors for atheroma formation in patients on hemodialysis.27,28 Although the effect of hemodialysis on the formation of calcified atheroma plaques has not been clarified, the presence of vascular calcifications in patients with end-stage renal disease on hemodialysis is associated with increased stiffness of large, capacitate, elastic-type arteries like the aorta and carotid.29 In addition, hemodialysis-related factors, such as using catheter and chronic inflammation due to high serum urea levels, may induce the formation of calcified atheroma plaques.30,31
In this study, CAC was observed in 23% of patients receiving hemodialysis on their digital panoramic radiographs. Of total patients, 34.2% were diagnosed with periodontitis (with CAC observed in 42.1% of patients with periodontitis) according to the new classification system24 with radiographic and clinical examinations. To the best of our knowledge, this study is the first to examine the relationship between periodontal status and presence of CAC in patients on hemodialysis with biochemical parameters. Similar to our results, the rates of CAC detected by digital panoramic radiographic examinations in patients on hemodialysis have been reported to range from 15.9% to 21.8%,32,33 whereas rates of CAC in the general population have been reported to range from 0.43% to 9.9%.34
There is a direct association between periodontitis-induced chronic inflammation and atherogenesis.35 It has been hypothesized that periodontal bacterial pathogens can enter the bloodstream, and by this way bacteremia is extremely important for the development and progression of atherosclerosis.36 The association between periodontal bone loss and CAC has been shown,37 and the correlation between CAC and periodontal risk has been evaluated.38 However, in the present study, for the correlations found between periodontal disease and CAC, periodontitis was diagnosed based on staging and grading. Our finding of correlation is not consistent with previous investigations that assessed the relationships among periodontal bone loss, periodontal risk, and presence of CAC.39 One reason for no correlation between groups with and without CAC may be because some patients are fully edentulous and, accordingly, when patients are divided into groups based on the periodontal status, the number of patients in the groups was insufficient.
In the present study, when clinical periodontal parameters were compared between patients with and without CAC, there was only statistically significant differences between the groups for probing pocket depth. Although the number of studies in the literature evaluating the relationship between CAC and clinical periodontal parameters in patients with hemodialysis is limited, our result is in agreement with 2 studies15,40 but inconsistent with results for probing depth in the general population.41 Increased probing pocket depth is a crucial clinical parameter in active periodontal disease.42 In studies that examined the relationship between coronary artery diseases and bone loss and periodontal clinical parameters, pocket depth and bleeding scores showed a stronger relationship than alveolar bone loss.15,41 Beck and colleagues showed that periodontal pocket depth >3 mm, generalized throughout the mouth, increased the risk of coronary heart disease.43 As they explained, a large number of gram-negative bacteria exist in deep pockets that not only directly invade periodontal tissues but also create broad opportunities for direct bacterial translocation and bacteremia with loss of epithelial integrity.44 Periodontal inflammation also induces the release of cytokines such as C-reactive protein, haptoglobin, fibrinogen, thromboxanes, interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor, which also pass into the bloodstream.45
All of these mediators can trigger platelet adhesion and aggregation and stimulate the formation of foam cells and accumulation of cholesterol in the arterial intima. By this way, periodontal disease promotes arteriosclerosis and thrombosis and increases the risk of cardiovascular disease.46 Additionally, Emingil and colleagues found that patients with periodontitis and probing depth of ≥4 mm had higher rates of myocardial infarction compared with controls.40
We observed that the duration of hemodialysis may be a risk factor in the presence of CAC independent of age. There are a limited number of studies in the literature evaluating the relationship between media layer thickness of carotid arteries and time on hemodialysis.47 It has been speculated that the correlation may be due to disturbances of the serum calcium-phosphate balance regarding the length of time in patients undergoing hemodialysis. Increased calcium-phosphate production in patients with advanced renal failure may induce both increased media layer thickness and calcium accumulation in the coronary arteries.48 In the present study, no significant difference was found between groups with and without CAC in levels of serum calcium and phosphate, which is consistent with previous observations.49 However, a limitation of our study was the simultaneous evaluation of serum levels along with periodontal and radiological examinations, and thus no significant difference could be found between the groups. The other factor for the higher incidence of atherosclerosis in patients with long hemodialysis duration may be increased free radical levels and decreased antioxidant levels in the bloodstream.50 Therefore, a retrospective examination of the clinical records of these patients and time-averaged blood tests may be more reliable than a single assessment to evaluate this relationship.
The formation of calcified atheroma plaques, which is a risk factor for cardiovascular diseases, tends to occur more frequently in patients undergoing hemodialysis treatment than in the general population. In addition, periodontal disease due to poor oral hygiene, which poses a risk for patients on hemodialysis, induces the formation of atherosclerosis. In this context, it is important to determine the presence of CAC in patients undergoing hemodialysis treatment. Panoramic radiographs are a noninvasive, easy, and reproducible method for determining the presence of CAC. In this study, the absence of a statistically significant difference between the groups in terms of periodontal disease and medical parameters may be due to our low number of patients. Therefore, further studies involving larger numbers of individuals diagnosed with periodontal disease according to the new classification are needed.
DOI : 10.6002/ect.2021.0119
From the 1Department of Periodontology and the 2Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Baskent University, Ankara; the 3Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Mersin University, Mersin; the 4Department of Oral and Maxillofacial Diseases and Surgery, Konya Execution and Research Hospital,Konya; and the 5Department of Nephrology, Baskent University Faculty of Medicine, Konya, Turkey
Acknowledgements: This study was approved by the Baskent University Institutional Review Board (D-KA 18/34) and supported by the Baskent University Research Fund. The authors have no declarations of potential conflicts of interest.
Corresponding author: Elif Inönü, Baskent University, Faculty of Dentistry, Department of Periodontology, Ankara 06490, Turkey
Phone: +90 312 2030000
E-mail: firstname.lastname@example.org, email@example.com
Figure 1. Digital Panoramic Radiograph Showing Unilateral Radiopacity of Suspected Carotid Calcification on Right Side