Associate Provost for Research Boston University Medical Campus
NIDCR - National Institute of Dental and Craniofacial Research	Research Resources

Abstract

Abstract: DESCRIPTION (provided by applicant): Epidemiological studies indicate that individuals with severe periodontal disease have significantly increased risk for cardiovascular disease. Periodontal disease, a chronic bacterial infection of the gums, is associated with recurrent bacteremia and a state of systemic inflammation that may convert endothelial cells to a pro-atherogenic phenotype with increased expression of inflammatory factors and loss of the anti-thrombotic, growth inhibitory, and vasodilator properties of the endothelium, including a decrease in the biological activity of nitric oxide. In human subjects, endothelial dysfunction has evolved into a well accepted indicator of early atherosclerosis and predictor of increased cardiovascular disease risk. We have recently demonstrated a strong association between severe periodontal disease and endothelial vasomotor dysfunction in a case control study of otherwise healthy human subjects. In that study, periodontal disease was also associated with higher plasma levels of the acute phase reactant C-reactive protein (CRP). These results support the hypothesis that severe periodontal disease induces a state of systemic inflammation that impairs endothelial function, however, the cross-sectional design leaves open the possibility that confounding factors explain the results. We now propose to determine whether effective treatment of periodontal disease improves endothelial function (Aim 1) and reduces inflammation (Aim 2) in a randomized intervention study. Patients will receive comprehensive periodontal treatment designed to produce a state of periodontal health (scaling and root planning and periodontal surgery with re-treatment as needed) or routine oral hygiene and will be followed for 24 weeks. The study will examine endothelium-dependent brachial artery flow-mediated dilation, systemic markers of inflammation and endothelial activation (CRP, IL-6, myeloperoxidase, and ICAM-1), and oral markers of periodontitis (PGE2, myeloperoxidase, and pathogen DNA) before and after treatment. Compared to oral hygiene (which will stabilize, but not reverse periodontal disease), we hypothesize that comprehensive treatment of periodontal disease will improve endothelium-dependent dilation and reduce local and systemic inflammation. Further, we suggest that the degree of improvement in endothelial function will relate to the degree of reduction in specific markers of inflammation. Such results would provide much stronger evidence for causal links between periodontal disease, systemic inflammation, and endothelial dysfunction, a recognized surrogate for cardiovascular risk. The proposed studies will provide new insights into how periodontal disease contributes to cardiovascular disease risk in human subjects and may lead to new approaches to therapy.

Thesaurus Terms:
cardiovascular disorder risk, human therapy evaluation, medical complication, oral pharyngeal surgery, periodontium disorder
acute phase protein, bacterial DNA, blood flow measurement, cardiovascular disorder prevention, cell adhesion molecule, clinical trial, dental plaque, interleukin 6, microorganism growth, myeloperoxidase, oral bacteria, periodontitis, preventive dentistry, vascular endothelium
blood chemistry, human subject, interview, nucleic acid quantitation /detection, patient oriented research, ultrasonography

Institution:	BOSTON UNIVERSITY MEDICAL CAMPUS
	715 ALBANY ST, 560
	BOSTON, MA 021182394
Fiscal Year:	2006
Department:	PERIODONTOLOGY & ORAL BIOLOGY
Project Start:	01-MAY-2004
Project End:	30-APR-2009
ICD:	NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
IRG:	ZDE1