Dottorato in TECNOLOGIE INNOVATIVE NELLE MALATTIE DELLO SCHELETRO,
DELLA CUTE E DEL DISTRETTO ORO-CRANIO-FACCIALE

Titolo della tesi: “Cross-sectional and Prospective Associations between Subclinical Atherosclerosis and Periodontal/Peri-implant Inflammation.”

Aims: While the association between periodontitis and systemic diseases is well known, little evidence is available on the potential impact of peri-implant diseases on systemic conditions. The aim of this dissertation was to investigate, either cross-sectionally and prospectively, the association between subclinical atherosclerosis, evaluated using the surrogate marker carotid intima media thickness (IMT), and periodontal and peri-implant diseases in a sample of patients suffering from primary hypertension. Material and Methods: In a first cross-sectional study, patients with primary hypertension and at least one dental implant with >5 years of functional loading were screened to evaluate their metabolic, periodontal and peri-implant status. A 24-hours ambulatory blood pressure monitoring and ultrasound assessment of carotid arteries were recorded for all patients, while anthropometric measurements and venous blood samples were obtained in the early morning after an overnight fast. Furthermore, every patient received a periodontal examination, collecting the Periodontal Screening and Recording (PSR) index in each of the sextants. After periodontal examination, patients were instructed to seek treatment of periodontal and peri-implant conditions diagnosed at their referring dental professionals. Only oral hygiene instructions were provided, and no further treatment was implemented. The diagnostic criteria of the ESC/ESH were adopted: arterial hypertension was defined as systolic BP (SBP) values ≥140 mmHg and/or diastolic BP (DBP) values ≥90 mmHg. Metabolic syndrome diagnosis was established in accordance with the NCEP ATP III criteria, while case definitions of the 2017 World Workshop were adopted for peri-implant and periodontal diseases. For each implant, probing pocket depths, mucosal redness, bleeding on probing, suppuration, plaque index and marginal bone loss were recorded. Using variables obtained at the baseline evaluation, a binomial logistic regression was performed to investigate the potential association between each parameter collected and the dependent variables (IMT > 0.9mm or IMT ≤ 0.9mm with the presence of carotid atherosclerotic plaque versus IMT ≤ 0.9mm and absence of atherosclerotic plaques (Model 1); IMT > 0.9mm versus IMT ≤ 0.9mm (Model 2); presence of carotid atherosclerotic plaque versus absence of carotid atherosclerotic plaque (Model 3). Correlation analyses between mean IMT values and cumulative PSR were further investigated using Spearman's rank-order testing. Then, a prospective cohort study was designed, contacting all patients evaluated two years before in the cross-sectional analysis, with an established diagnosis of periodontitis and peri-implant diseases. Among patients successfully recalled, a complete follow-up medical visit was conducted, collecting new biomarkers and performing a novel vascular assessment. The comparison between medical parameters collected at baseline and follow-up was assessed by Mann-Whitney U test for continuous variables and by Chi-square test of homogeneity and Fisher's exact test for categorical variables. Then, a multiple regression (backward stepwise) was performed to ascertain the effects of independent variables on average IMT as continuous outcome. Statistical significance was set at p≤0.05. Results: A total of 151 patients had complete available data on their hypertensive state at the baseline evaluation. In the cross-sectional analysis, three different statistical models were used to determine which independent predictors were associated with increased values of IMT. Periodontitis (OR ranging from 3.43 to 8.97) and cumulative PSR values (OR range: 1.19-1.32) were statistically significant in all models adopted, while peri-implant mucositis was found to be significant in Model 1 (OR= 3.34) and Model 2 (OR= 3.05) and peri-implantitis was not statistically significant in any model. In the linear regression model, a positive significant association with increased IMT was found out for cumulative PSR values (β=0.011, SE 0.002, p<0.001), presence of periodontitis (β=0.114, SE 0.020, p<0.001) and presence of peri-implant diseases (when considering mucositis and peri-implantitis aggregated) (β=0.011, SE 0.002, p<0.001). In this scenario, gingival inflammation was strongly related with systemic inflammation, as outlined by the Spearman's rank-order correlation (rs = .354; p < 0.001). In the prospective analysis, 71 patients were successfully recalled. Among parameters investigated, only IMT values were statistically significant higher (p= 0.015) at follow-up when compared with baseline (mean IMT values of 0.76 ±0.13 mm, 0.88 ± 0.19 mm, respectively). The linear regression model revealed a positive significant association with increased IMT and cumulative PSR values, CRP, Triglycerides and Creatinine, with an R2 = 0.863. Conclusions: Based on the results of the cross-sectional analysis, gingival inflammation, expressed as cumulative PSR, was strongly associated with higher IMT values and plaque presence, reporting for the first time an association with peri-implant diseases. Based on the results of the prospective analysis, we can cautiously conclude that gingival inflammation is related with the progression of subclinical atherosclerosis. Among a cohort of patients untreated for periodontitis and peri-implant diseases, with no differences for hypertensive and lipidic profiles and medications taken, there was a mean progression rate of 0.06 mm/year during the two years observation period, consistently higher compared to values reported in large epidemiological studies. When taking into account all cofounding variables, the linear regression model revealed a positive significant association with increased IMT and cumulative PSR values, CRP, Triglycerides and Creatinine.