Periodontal status and host susceptibility to systemic comorbidity : 'co-expression' patterns, frailty biomarkers & perspectives

Abstract

Periodontal disease as a major oral disease burden worldwide markedly impacts oral health, and closely links to various systemic diseases, through the plausible mechanisms of infection, inflammation, dysbiosis and commonly shared risk factors. The present study investigated the potential effect of periodontal disease on the onset and progression of overall systemic comorbidity on an individual basis, and further identified potential frailty biomarkers of host susceptibility to periodontitis and common systemic comorbidities. Firstly, the 18-year follow-up cohort study on 488 subjects with various periodontal status indicates that the experience and existence of periodontal disease significantly increase the risk for the onset and occurrence of common systemic comorbidities (Chapter III). Next, the cross-sectional study with a larger sample size (1,189 subjects) holistically explores the association of periodontal status with the overall comorbidity profiles, and finds that periodontal conditions could reflect multiple combinations of systemic comorbidities (Chapter IV). The study on 115 self-reported healthy subjects highlights that vast majority of the participants are in fact unaware of their existing common systemic abnormalities, and importantly the presence of severe periodontitis is independently associated with simultaneously existing systemic abnormalities with adjustments of potential confounders (Chapter V). Additionally, 95 subjects were recruited to intentionally match critical covariates (age, gender, household income level and cigarette smoking) with the above-mentioned 115 subjects, and finally 50 Severe Periodontitis patients (cases) and 50 Non-severe Periodontitis subjects (controls) were included. Furthermore, the assays for investigating a series of potential frailty biomarkers reveal that patients with Severe Periodontitis and worse systemic conditions have considerably higher serum level of CCL24 than the counterparts. Crucially, subgroup analysis further demonstrates that CCL24 may act as an independent biomarker for severe periodontitis and ongoing systemic comorbidities (Chapter VI). Moreover, the cardiovascular function of those subjects described in Chapters V and VI was evaluated. The surrogate measures including arterial stiffness (mean pulse wave velocity), left ventricular hypertrophy (mass index) and diastolic dysfunction (E/A ratio) as well as right ventricular dysfunction (tricuspid annular plane systolic excursion) were significantly worse in subjects with poor periodontal conditions than those in the counterparts. These findings collectively suggest that severe periodontitis could link to compromised cardiovascular function (Chapter VII). The present study provides the first evidence that the experience and existence of periodontal disease could to some extent reflect the onset and simultaneous occurrence of common systemic comorbidities, and CCL24 may be a frailty biomarker of host susceptibility to periodontal disease and overall systemic comorbidity. Yet, compromised periodontal conditions may contribute to increasing the risk for cardiovascular dysfunction. The current work shows new evidence on the interconnection of periodontal status with overall profiles of systemic comorbidities, and enhances the current notion for understanding host susceptibility to periodontal disease and poor general conditions. The present findings may contribute to further identifying and developing frailty biomarkers for assessment of individual susceptibility to periodontal disease and systemic comorbidity, thereby promoting precision healthcare for optimal oral/periodontal health and general wellbeing.