Periodontal treatment and reduction of vascular inflammation in patients with PAD

Scientific background: At least three meta-analyses have demonstrated a positive association between periodontal disease and atherosclerotic vascular disease such as coronary heart disease, stroke and peripheral arterial disease (PAD). We were able to show that treatment of severe periodontitis reversed endothelial dysfunction accompanied by a significant decrease in C-reactive protein concentrations in otherwise healthy subjects. Although there is epidemiologic evidence that periodontitis is significantly associated with PAD and despite the detection of periodontopathic bacteria in atherosclerotic specimen, no randomized, controlled trial has been designed to test the hypothesis that periodontal therapy reduces vascular inflammation in PAD. Hypothesis: We hypothesize that treatment of periodontitis reduces cardiovascular biomarkers and vascular inflammation as shown by reduced F-fluorodeoxyglucose (FDG) uptake in atherosclerotic plaque of patients with PAD in whole-body positron emission tomography (PET). Study design: Consecutive patients with PAD will be screened for the presence of periodontitis. Subjects who meet the inclusion criteria of severe Periodontitis will be invited to participate in the study. Patients will be randomized to the periodonatal therapy group or to the community dental care group. In the periodontal therapy group non-surgical treatment will be performed. Participants randomized to the community dental care group will be advised to seek the opinion of a dentist after the FDG-PET/CT follow-up examination. FDG-PET/CT will be performed in the periodontal therapy group before and three months after periodontal treatment. In the community dental care group FDG-PET/CT imaging will be performed at baseline and after three months. Thereafter, community dental care will be recommended in a letter stating the tentative diagnosis. Primary endpoint will be reduction of vascular inflammation as measured by target to background ratio (TBR) of PET FDG uptake. Secondary endpoints will be reduction of cardiovascular biomarkers and data on feasibility including data on compliance, periodontal and cardiovascular outcomes, and adverse events. Potential prospective impact: The results of our study will elucidate the impact of periodontal therapy on the reduction of vascular inflammation. Since inflammation plays a critical role in atherosclerotic plaque initiation, progression, and disruption, a procedure that reduces vascular inflammation may reduce cardiovascular morbidity and mortality.

A number of research activities have addressed the possible impact of periodontal disease on coronary, cerebrovascular, and peripheral arterial disease. Since both periodontal and cardiovascular diseases are common, a causal relationship would be of great importance for the prevention of life threatening events like myocardial infarction and stroke. Since inflammation is important in the development and progression of both periodontal and cardiovascular diseases, we have designed a study to evaluate, if the treatment of periodontitis reduces inflammation in the vessel wall. Inflammation was studied in the carotid and lower limb arteries and in the thoracic and abdominal aorta by positron emission computed tomography (PET/CT) before and after periodontal therapy. 409 patients with peripheral arterial disease were screened for the presence of gingivitis or periodontitis. Only one patient had no sign of periodontal disease. Finally, 90 patients with more advanced periodontal disease were included in the randomized-controlled trial. Periodontal treatment was performed with and without additional antibiotic therapy and has reduced the extension of periodontitis especially when antibiotic therapy was prescribed in addition to mechanical treatment. However, there was no reduction of inflammation in the vascular segments studied by PET/CT. Furthermore, we found no reduction of concentrations of systemic markers of inflammation and other vascular biomarkers after periodontal treatment. Nevertheless, the findings of our study are important. For patients with periodontitis we were able to demonstrate that antibiotic treatment in addition to non-surgical mechanical therapy improved periodontal outcomes. For the management of vascular disease patients it is important to understand that the prevalence of periodontal diseases is unexpectedly high. Periodontal treatment in this cohort is important in order to improve oral health and prevent tooth loss. However, we found no evidence that periodontal therapy reduced vascular inflammation in the vessel wall that might trigger cardiovascular events like myocardial infarction or stroke.