Observational Study of the Association Between Periodontal Disease and Cardiovascular Disease

A possible association between periodontal disease and cardiovascular disease was first hypothesized in the 1980s. Epidemiological studies performed over the last 20 years have shown a strong correlation between periodontal disease and cardiovascular disease. However, the literature is somewhat divided, as some studies have shown moderate correlation while others have shown independent (insignificant) correlations between the two. This leaves a gap in the investigators knowledge that must be brought together through specific studies. There have been reports made to suggest that 52% of atherosclerotic plaques studied have been found to contain the same pathogens that cause periodontitis. This is the reason that these are the bacteria that will be focused on during the course of this study.

Periodontal disease, known as either gingivitis or periodontitis, is caused by the presence of bacteria in the gingival pockets in the mouth which over time can cause systemic inflammation through endotoxin production. Some examples of the bacteria that cause periodontal disease include Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. These are gram-negative, anaerobic bacteria that are able to thrive in the sub-gingival space after they are able to successfully become established. These two bacteria have been known to invade oral epithelial cells, creating the possibility that they could invade epithelial cells elsewhere such as in coronary vessels. These bacteria will be cultured from the patient and the relative amounts of them as determined by culture techniques will be used to assess the prevalence of periodontal disease in the patient. P. gingivalis is of special importance because it is known to be found in patients with active periodontal disease and not commonly found in patients without periodontal disease. It can be identified by the black pigment produced upon culture. Tryptic Soy-Serum-Bacitracin-Vancomycin (TSBV) Agar is a selective medium that is able to isolate A. actinomycetemcomitans. The identity of A. actinomycetemcomitans can be confirmed based on the growth of "star-like" colonies on the TSBV Agar that are catalase positive. The relative amount of these bacteria as determined by culture will be used to correlate with the level of coronary artery disease based on the groups that each subject is assigned to. This is how the basis for an association between the two conditions can be determined.

Systemic inflammation occurs as a result of the release of pro-inflammatory cytokines in response to an infection. Some of the cytokines released, include high sensitivity C-reactive protein (hs-CRP), interleukin-1 (IL-1), and interleukin-6 (IL-6). Hs-CRP is a protein that is active during the acute phase response to inflammation. Its level in the blood has been shown to be markedly raised in chronic inflammation and has consistently been found to be elevated in patients with acute coronary syndromes. IL-1 is a pro-inflammatory cytokine that is also released as a result of systemic inflammation. Specifically, it has been found to be secreted in response to lipopolysaccharide (LPS) from gram-negative bacteria and has been found to be elevated in patients with increased periodontal disease. IL-6, like IL-1, is a pro-inflammatory cytokine that is part of the acute phase response to infection. It has been strongly correlated with increasing levels of coronary artery disease and has even been demonstrated as a predictive marker of mortality in Coronary Artery Disease (CAD). In addition to its role in CAD, IL-6 has also been found to be elevated in periodontal disease, creating the possibility for the basis of the link between these two diseases.

The aim of this study is to achieve a better understanding of the relationship between periodontal disease and coronary artery disease by correlating the severity of coronary artery disease with the presence and amount of the periodontal pathogens P. gingivalis and A. actinomycetemcomitans. The level of systemic inflammation caused by these pathogens and and coronary artery disease will also be assessed. This will determine if coronary artery disease can be associated with one of these specific pathogens more than the other and what levels of systemic inflammation can be associated with both of these conditions together.

Samples will be obtained from periodontal tissue, cultured, and the amount of the specified pathogens present will be correlated with the type and extent of the patient's cardiovascular disease. Blood tests will also be taken to assess the level of systemic inflammation occurring as a result of periodontal disease and cardiovascular disease.