$7.3 Million Grant to Fund First Clinical Study of Effect of Periodontal Treatment on Heart-Disease Risk

Five-center study will lay groundwork for large-scale clinical trial

By Lois Baker

Release Date: October 3, 2001

BUFFALO, N.Y. -- The University at Buffalo has received a $7.3 million, three-year grant from the National Institute of Dental and Craniofacial Research to plan and conduct a pilot study for a clinical trial of the impact of periodontal disease treatment on prevention of second heart attacks.

The three-year effort, involving five centers, will set the stage for a definitive clinical trial on a larger scale of the relationship between periodontal infection, which affects 75 percent of Americans, and cardiovascular disease.

Robert J. Genco, D.D.S., Ph.D., chair of the Department of Oral Biology in the UB School of Dental Medicine and a SUNY Distinguished Professor, is principal investigator on the grant.

UB is leading the study, which also involves the University of North Carolina at Chapel Hill, Boston University, Kaiser Permanente/Oregon Health Science University and the University of Maryland.

"We are extremely pleased by this $7.3 million grant from the National Institute of Dental and Craniofacial Research in support of this groundbreaking study," said UB President William R. Greiner. "Bob Genco has long been a pioneer in the field, and we are delighted that this grant will allow him to put together and lead this distinguished multi-institutional research team."

UB Provost Elizabeth D. Capaldi noted, "This exciting work has the potential of identifying a new risk factor for heart disease, one that is treatable and thus will have a profound impact on the health of Americans. We are pleased that the institute has recognized the great potential of this work and provided the funding."

Genco said the grant "provides an opportunity to bring the basic research we have been doing at UB on periodontal infection and its potential effect on the risk of heart disease and stroke into the real world of the clinic," said Genco.

"If we find through this pilot study that keeping gum disease in check appears to lessen the chances of a second cardiovascular incident, we will be justified in proposing a large-scale clinical trial that should provide definitive answers on the relationship between these two chronic conditions.

"If the study is positive, it will give us one more weapon in the battle against heart disease," Genco said. "However, we are a long way from having the data necessary to suggest that treatment of gum disease or any infection will reduce heart disease."

The grant will allow Genco and co-investigators to assemble the team of cardiologists, periodontists, epidemiologists, infectious-disease specialists, biostatisticians, research nurses in periodontics and cardiology, and data managers necessary to carry out a full-blown periodontal intervention trial.

Co-investigators, all from UB, are Maurizio Trevisan, M.D., professor and chair of the Department of Social and Preventive Medicine and interim dean of the School of Health Related Professions; Susan Graham, M.D., associate professor of medicine; Sara Grossi, D.D.S., clinical assistant professor of oral biology; Joseph J. Zambon, D.D.S., Ph.D., professor of periodontics and endodontics, and Paola Muti, Ph.D., M.D., associate professor of social and preventive medicine.

Genco said the planning period and pilot study are intended to form the foundation for a definitive trial to answer the question: "If periodontal infection is suppressed by an anti-infective intervention, will this result in decreased risk of heart disease?

"It is important to answer this question in a clear and definitive fashion before any clinical decisions are to be made to treat periodontal disease for general health reasons," he said.

The pilot clinical trial will begin after a nine-month planning and development period. It will include three groups of subjects: a group that will receive antibiotic therapy directed to suppressing the local gum infection; a group that will receive local therapy plus treatment with the systemic antibiotic azithromycin, and a group that will receive standard dental care.

The investigators will assess a risk factor for heart disease, the C-reactive protein, which also may be related to periodontal infection.

A total of 900 persons who have periodontal disease and have had one heart attack or are otherwise at high risk for a cardiovascular event will be recruited for the trial by the five centers. The pilot trial will be used to refine the infrastructure and to select or refine an intervention protocol for the definitive trial, Genco said.

Epidemiological studies conducted at UB and elsewhere have shown an association between various measures of poor dental health and coronary disease, even after accounting for other risk factors. A 1999 study using data collected nationwide through the Third National Health and Nutrition Examination Survey, for example, found that people with the severest periodontal disease were nearly four times more likely to have had a heart attack than people with no periodontal disease.

Genco's research team at UB, in one of several studies, assessed the presence of specific oral bacteria in heart-attack patients compared to healthy controls. They found that two periodontal bacteria -- Porphyromonas gingivalis and Bacteroides forsythus -- were associated with a 2.5 and 3.0 increase in risk, respectively, of heart attack.

Periodontal disease is common in the U.S. Seventy-five percent of the population suffers mild forms, while 20-30 percent has more severe forms, according to the most recent statistics from the national health survey

"There is growing evidence of a relationship between infection and atherosclerosis, as well as a specific link between periodontal infection and heart disease," Genco said. "Previous studies have established possible effective treatments of periodontal disease, and it is possible these treatments may lead to a fewer subsequent myocardial events in people at high risk for cardiovascular disease.

"Our study is designed to select the periodontal treatment with the best chance of reducing the risk for heart disease."