Re: earlier study:

"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."

Comment. It appears that there is still great interest in studying the
role that systemic inflammation resulting from periodontal disease may
play in endothelial impairment, known to lead to atheriosclerosis and
coronary artery disease.  Current evidence supports looking at this
further, via a multicenter trial.  If this goes to Phase III, 1000-
3000 will be enrolled.

I am very excited to follow this larger trial.

-Sue (nondentist)

Official Title: Systemic Endothelial Consequences of Periodontal
Disease

Further study details as provided by National Institute of Dental and
Craniofacial Research (NIDCR):
Primary Outcomes: Periodontal disease contributes to cardiovascular
disease risk in human subjects and may lead to new approaches to
therapy.
Expected Total Enrollment:  160
Study start: September 2004;  Expected completion: May 2009
Last follow-up: April 2005;  Data entry closure: May 2009

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 planing 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.