New Study Further Strengthens Link Between Gum Disease And Early Indicators Of Cardiovascular Disease

Research Published in New England Journal of Medicine Demonstrates Benefits of Intensive Periodontal Treatment Warminster, PA (March 1, 2007) – Researchers may be one step closer to establishing a link between periodontal disease and cardiovascular disease (CVD) – the number one cause of death worldwide. According to a new study unveiled today in the New England Journal of Medicine, periodontal disease contributes to blood vessel dysfunction, which was improved by an intensive regimen of periodontal treatment. The research team, led by Maurizio Tonetti, D.M.D., Ph.D., executive director of the European Research Group on Periodontology, demonstrates a link between early indicators of arthrosclerosis (hardening of the art periodontal disease.

The study enrolled 120 otherwise healthy patients with a severe form of periodontitis in a six-month trial and compared the effects of regular tooth cleaning with those of intensive periodontal treatment (scaling and root planing, locally administered antibiotics and tooth extraction, when necessary). The intensive treatment group showed important and statistically significant improvements in blood flow (as measured by brachial arterial dilation) within two months of treatment. The improvement was greater six months after treatment. "In recent years, there have been numerous hypotheses linking periodontal infections to atherosclerosis – the process that leads to blockage of blood vessels," notes Dr. Tonetti. "This study validates the effectiveness of intensive periodontal treatment in affecting vascular health."

Currently, more than one in three Americans over age 30 have some form of periodontitis, according to the American Academy of Periodontology. CVD is the single largest killer of American adults; in 2003, it caused one of every five deaths in the United States. Unfortunately, periodontal infections often go untreated, creating a chronic inflammatory burden that may result in systemic inflammation, possibly contributing to broader health problems. "The study published in the New England Journal of Medicine is promising for patients, as well as for the medical and dental communities," notes periodontist Michael C. Lynch, DMD, Ph.D., director, Clinical Research Rx, New Technology Oral Health Care Research & Development, of OraPharma, Inc., whose locally applied antibiotic, ARESTIN® (minocycline HCl) Microspheres, 1 mg, was selected by Dr. Tonetti for use in this study. "While researchers continue to study the link between systemic disease and oral health, this study adds to the growing body of evidence and underscores the potential impact of infection and subsequent inflammation on systemic diseases." "OraPharma's mission is to advance oral health and improve overall health through innovative products and services for the dental professional," adds Russell Secter, PharmD, president, OraPharma, Inc. "We are excited by the results of this study and will continue to support research in this area."

Results of the clinical trial by Dr. Tonetti and colleagues are reported in the March 1 issue of the New England Journal of Medicine (NEJM). The team of independent researchers that completed the study includes: Maurizio S. Tonetti, D.M.D., Ph.D., Francesco D'Aiuto, D.M.D., Ph.D., Luigi Nibali, D.M.D., Ph.D., Ann Donald, Clare Storry, B.Sc., Mohamed Parkar, M.Phil., Jean Suvan, M.Sc., Aroon D. Hingorani, Ph.D., Patrick Vallance, M.D., and John Deanfield, M.B., B.Chir. As reported in the NEJM, this study was funded by leading academic and research institutions, as well as by an educational grant from OraPharma, Inc.

OraPharma, Inc., is a specialty pharmaceutical company that discovers, develops and commercializes therapeutics for oral health. OraPharma, Inc., is dedicated to the dental community, specifically the periodontal space.

Treatment of Periodontitis and Endothelial Function - Abstract

Maurizio S. Tonetti, D.M.D., Ph.D., Francesco D'Aiuto, D.M.D., Ph.D., Luigi Nibali, D.M.D., Ph.D., Ann Donald, Clare Storry, B.Sc., Mohamed Parkar, M.Phil., Jean Suvan, M.Sc., Aroon D. Hingorani, Ph.D., Patrick Vallance, M.D., and John Deanfield, M.B., B.Chir. ABSTRACT

Background Systemic inflammation may impair vascular function, and epidemiologic data suggest a possible link between periodontitis and cardiovascular disease.

Methods We randomly assigned 120 patients with severe periodontitis to community-based periodontal care (59 intensive periodontal treatment (61). Endothelial function, as assessed by measurement of the diameter of the brachial artery during flow (flow-mediated dilatation), and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1, 7, 30, 60, and 180 days after treatment.

Results Twenty-four hours after treatment, flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group (absolute difference, 1.4%; 95% confidence interval [CI], 0.5 to 2.3; P=0.002), and levels of C-reactive protein, interleukin-6, and the endothelial-activation markers soluble E-selectin and von Willebrand factor were significantly higher (P<0.05 for all comparisons). However, flow-mediated dilatation was greater and the plasma lev of soluble E-selectin were lower in the intensive-treatment group than in the control-treatment group 60 days after therapy (absolute difference in flow-mediated dilatation, 0.9%; 95% CI, 0.1 to 1.7; P=0.02) and 180 days after therapy (difference, 2.0%; 95% CI, 1.2 to 2.8; P<0.001). The degree of improvement was associated with improvement in measures of periodontal disease (r=0.29 by Spearman rank correlation, P=0.003). There were no serious adverse effects in either of the two groups, and no cardiovascular events occurred.

Conclusions Intensive periodontal treatment resulted in acute, short-term systemic inflammation and endothelial dysfunction. However, 6 months after therapy, the benefits in oral health were associated with improvement in endothelial function.