factors for CVD. ⁵ And contrary to the long-held belief patients with significantperiodontalbacterialburden had
that CVD is primarily induced by hypercholesterolemia, increased carotid intima-media thickness (IMT), ¹⁶ which
high cholesterol is relevant in only 50% of patients with is an indicator of subclinical (undetected) atherosclerosis
coronary artery disease (CAD). ⁶ As a result, researchers and a precursor to CVD.
are aggressively pursuing other biological mechanisms
that may implicate less obvious, more novel risk factors One of the most reliable markers of systemic inflammation
for CVD. is high sensitivity C-reactive protein (hsCRP), which is
one of the acute phase proteins that is produced by the

In Search of Novel Risk Factors for CVD liver in response to ischemia, trauma, burns, infections, One of the biological mechanisms under investigation is and other inflammatory conditions. ⁷ C-reactive protein the role periodontal infection may play in increasing the (CRP) is an independent risk factor for CVD. ¹⁷ The risk for CVD. During the last 20 years, many case-control growing consensus is that testing CRP levels in the blood and cross-sectional studies have shown have association with high sensitivity assay (hsCRP), which is now widely between periodontal disease severity and CVD. ⁷ It has available, can consistently predict new coronary events been known for some time that there is a biological in patients with unstable angina and acute MI. ¹⁸ It has gradient between periodontal infection and the incidence also been suggested that increased hsCRP will elevate an of CHD and a dose relationship between various levels individual at intermediate risk for CVD within 10 years of bone loss and the cumulative incidence of angina and to a higher risk category. ¹⁸ Recent research indicates MI. ⁸ that there may be a gradient effect between the extent and severity of periodontal disease and elevated levels of

Although many research findings point to intriguing hsCRP¹⁹ and that the presence of CVD seems to be highest
evidence of a relationship between periodontal disease in those individuals in whom periodontal disease co-
and CVD, a cause-and-effect relationship has yet to exists with elevated hsCRP. ²⁰ Patients with periodontitis
be proven. Experts at the 2003 American Academy of have increased systemic levels of hsCRP and fibrinogen,
Periodontology (AAP) Workshop on Contemporary Science both of which affect coagulation, platelet activation, and
in Clinical Periodontics concluded that although there was aggregation contributing to atheroma formation, thereby
a moderate level of evidence to suggest that periodontal increasing the risk for CVD. ^{21, 22}
disease is associated with CVD, additional large-scale
longitudinal epidemiological and intervention studies It is true that randomized controlled clinical trials to
are necessary to validate the association. 9 What still demonstrate the potential cardiovascular benefits of
remains a mystery is whether the association is causative periodontal treatment are needed before sweeping
or because of etiological factors common to both disease changes in health-care policy can be established. Some
processes. ⁹ The consensus opinion of the 2003 workshop of this research, in fact, may be on the way. The National
stated there was insufficient evidence to support advising Institute of Dental and Craniofacial Research (NIDCR)
patients that periodontal treatment could prevent the has just completed but not yet reported the findings of
onset or progression of atherosclerosis-induced diseases a study of 400 participants called PACE (Periodontitis
like CVDandstroke. ⁹ and Cardiovascular Events) to determine if treating
periodontal infections will lead to fewer MIs, cardiac

Since the consensus findings of the 2003 AAP workshop, revascularization, fatal coronary disease, unstable angina mounting evidence reported in dental and medical journals and hospitalized ischemic stroke. ²³ This pilot clinical seems to strengthen the supposition that periodontal trial, involving investigations at five university treatment bacterial pathogens and the resulting host immune facilities, will provide supporting data for the development response are directly implicated in the development of a larger randomized clinical trial that will include about of atherosclerosis and in the increased risk for cardio- 4,000 participants from 15 academic centers across the and cerebrovascular events. ^10-15 The Oral Infections and United States. ²³

Vascular Disease Epidemiology Studies (INVEST) published within the last few years have provided more substantial Another study that is especially intriguing is being evidence that periodontal disease may actually accelerate conducted at Boston University. Also sponsored by NIDCR, the development of atherosclerosis-related diseases (i.e. this study is designed to determine whether effective CVD and stroke). ¹⁶ The INVEST studies also reported that treatment of periodontal disease improves endothelial