Background
Aortic aneurysm (AA), by definition, is local or diffuse aortectasia with at least 1.5 times the expected normal vascular diameter [
1,
2]. AA may occur at any portion of the arterial system, including central arteries (e.g., thoracic aorta and abdominal aorta) and peripheral arteries (e.g., cerebral artery, the artery of extremities and visceral artery) [
1]. AA, more commonly seen in the developed countries, is a critical condition with a male predominance and a high mortality rate once ruptures (~ 90%) [
2,
3]. AA is a multifactorial disease. Risk factors for aneurysmal dilatation include trauma, infection, chronic inflammation (e.g., atherosclerosis), connective tissue disorders (e.g., Marfan syndrome) and environmental factors (e.g., smoking) [
4,
5]. Clinically, AA is strongly associated with atherosclerosis, and share similar risk factors [
2]. The atheromatous plaque erodes the aortic wall, destroys the arterial media and results in degeneration of elastic fibers [
2,
6]. Infection and chronic inflammation may play a critical role in the initiation and development of AA [
2]. Periodontitis is a chronic inflammatory disease caused by pathogenic bacteria and is correlated with cardiovascular diseases, such as atherosclerosis and AA [
7]. In addition, periodontal pathogens were identified in the vascular samples from AA patients [
8]. Due to the ageing of the population, changes in the lifestyles, and rise of the number of smokers, the incidence of AA in China has increased in the past few decades [
9]. Thus far, epidemiological studies exploring the association between AA and periodontal diseases in the Chinese population have never been done. Our cross-sectional study aimed to investigate the periodontal conditions in AA patients, and further explore the correlation between AA and chronic periodontitis in the Chinese population.
Methods
Study population
Patients with aortic aneurysm (AA) were diagnosed and recruited from the Center for Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University between Jan 2012 and June 2016. This study was approved by The Institutional Review Board of Ethics Committee of Beijing Anzhen Hospital, Capital Medical University. All participants received written and oral information prior to giving written consent, and the study was performed in accordance with the Helsinki II declaration. AA was detected and diagnosed by computed tomography (CT) when the aortic diameter was 50% greater than the expected normal size. Non-AA volunteers were recruited from the health examination center as the control subjects. To diagnose chronic periodontitis, we followed the Classification of Periodontal Diseases and Conditions published by the International Workshop in 1999 [
10]. Based on the level of destruction, chronic periodontitis is graded as mild (periodontal pocket depth ≤ 4 mm, clinical attachment loss (CAL) 1–2 mm, and alveolar resorption < 1/3 of root length), moderate (periodontal pocket depth ≤ 6 mm, CAL 3–5 mm, and alveolar resorption 1/3–1/2 of root length) and severe (periodontal pocket depth > 6 mm, CAL ≥ 5 mm, and alveolar resorption ≥1/2 of root length) [
11]. Patients were excluded if they had periodontal treatments in the past six months and continuous antibiotics applications in the past three months, pseudo-aneurysm, and aortic dissection, or systemic diseases (e.g., malignant tumors, hepatitis and respiratory system disease).
Questionnaire
A questionnaire was administered on all the subjects to collect general information (e.g., height, weight, education, socioeconomic status, smoking, and alcohol consumption), past medical history, history of chronic periodontitis and periodontal treatments, and dental hygiene habits. All the investigations were conducted under the clinical protocols: 2012001X, 2015011X, and 2017027X approved by the ethics committee of Beijing Anzhen Hospital, Capital Medical University. We have obtained the consent from both AA patients and non-AA volunteers before the investigation.
Periodontal examination
The periodontal examinations were completed by the same periodontist. Plaque index (PlI), bleeding index (BI), probing depth (PD) and CAL were examined and recorded at six sites (mesial-buccal, mid-buccal, distal-buccal, mesial-lingual, mid-lingual, and distal-lingual sites) of the Ramfjord index teeth (i.e., maxillary first molar, maxillary central incisor, maxillary first premolar, mandibular first molar, mandibular central incisor, and mandibular first premolar) [
10]. In addition, missing teeth (excluding third molars) were recorded.
Statistical analysis
The data were collected and analyzed using the single-blind method by SPSS 13.0 software (SPSS Inc., Chicago, IL, USA). The measurements were demonstrated as a mean ± standard deviation and analyzed using t-test. Independent t-test was utilized for the inter-group comparison, and variance analysis was used for the comparison of multiple groups. Using AA as the dependable variable and all the potential risk factors (e.g., gender, age, and CAL) as covariates, a logistic regression analysis was performed to determine whether the periodontal infection was one of the risk factors for AA. p < 0.05 was considered significant.
Discussion
Dental diseases are correlated with cardiovascular disorders, such as atherosclerosis-induced acute myocardial infarction [
12‐
14]. A potential connection between periodontal diseases and cardiovascular disorders was proposed in the 1990s, followed by multiple studies supporting this hypothesis in the past two decades [
15,
16]. In addition, moderate to severe periodontal diseases have been demonstrated as a significant independent risk factor for peripheral arterial diseases [
17]. AA, a cardiovascular disorder, is highly associated with chronic inflammation and infections [
2]. Thus far, many studies have indicated that chronic periodontitis contributes to the initiation and progression of AA [
2,
7,
8]. Consistent with the previous observations, in the cohort of our current studies, 148 AA patients exhibited chronic periodontitis (87.6%), which was significantly higher than that in the non-AA group (55.8%). Compared to the non-AA subjects, AA patients exhibited poorer periodontal health, namely more missing teeth, greater PlI and CAL indices and a higher degree of periodontal damages (69.2% moderate to severe chronic periodontitis), suggesting chronic periodontitis is a risk factor for AA incidence.
Studies have revealed that periodontal pathogens, herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Chlamydia pneumoniae may be closely associated with the initiation and progression of AA [
18]. Periodontal pathogens,
Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), were detected in 7.1% of the AA samples [
19,
20]. Other bacteria species,
Porphyromonas gingivalis (P. gingivalis),
Treponema denticola,
Tannerella forsythia, Prevotella intermedia, and
Campylobacter rectus, were also identified in the AA samples [
21]. Both P. gingivalis and A. actinomycetemcomitans have been successfully recovered and cultivated in the atherosclerotic tissues [
22].
Periodontal pathogens were found in atherosclerotic lesions of the peripheral and central arterial systems [
23]. In addition, periodontal pathogens were discovered in the AA samples, suggesting a bacterial invasion of an existing aneurysm by transient bacteremia [
23]. Pathogenic microorganisms play a critical role in the initiation and progression of AA, and oral cavity and periodontal pocket may serve as the niche for these gram-negative bacteria [
23]. Two hypotheses have been put forward to explain the etiopathological mechanisms of periodontitis-induced AA. The infection hypothesis proposed that microorganisms contribute to the AA pathogenesis [
23]. Pathogenic bacteria from subgingival dental plaques are introduced into the bloodstream through daily activities (e.g., chewing and tooth brushing). Bacteria-induced inflammatory infiltrates then interact with the microenvironment, leading to the production of cytokines and matrix metalloproteinases (MMPs), and degeneration of collagen fibers in the arterial walls [
19,
23]
. The second hypothesis proposed that periodontal pathogens discovered in the aneurysmal tissues were secondary to the short-term bacteremia invading the existing AA [
24].
A clinical study was done to examine the prevalence of periodontitis in patients with abdominal AA or arrhythmia in the Japanese population [
25]. The results demonstrated that periodontitis had greater impacts on abdominal AA progression, in comparison with other cardiovascular diseases (e.g., arrhythmia) [
25]. Compared to the patients with arrhythmia, the AA patients exhibited fewer well-maintained teeth (14.6 ± 2.0 vs. 20.9 ± 0.7,
p < 0.05) and deeper periodontal pockets (3.01 ± 0.26 vs. 2.52 ± 0.05 mm,
p < 0.05) [
25]. In addition, in another age- and gender-matched study in the Japanese patients, periodontal bacteria were detected in both abdominal AA and non-AA patients, but deeper periodontal pocket depth was identified in the AA patients [
26]. Though with small sample size in these studies, the results indicated a correlation between periodontitis and AA, which is similar to our findings in the current study.
AA and coronary heart diseases share common risk factors, such as age, gender, smoking, diabetes, BMI, hypertension, and hyperlipidemia, which can also be confounding factors in the periodontal research [
27,
28]. However, the pathogenesis of AA cannot be fully explained by these risk factors. In the current study, we have adjusted these risk factors in the multivariate analysis (OR = 2.309, 95% CI: 1.623–3.284,
p = 0.000), and discovered that CAL is an independent risk factor for AA. Our results indicated the existing periodontal infections can be another risk factor in the development of AA.
Multiple studies have shown the association of periodontal conditions with AA [
8,
20,
25], but this is the first study investigating the correlation between oral hygiene habits and AA in the Chinese population. Our results indicated that improper oral hygiene habits, such as inaccurate brushing method, no dental flossing, and no regular supra-gingival scaling, are correlated with the incidence of AA.