It is our central hypothesis that periodontal diseases, which are chronic gram-negative infections represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events Previous studies have demonstrated an association between periodontal disease severity and risk of coronary artery disease and stroke. We hypothesize that this association may be due to an intrinsic underlying inflammatory response trait that places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (LPS, lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL- 1B, PGE2 and TNFa) which serve to initiate and exacerbate atherogenesis and thromboembolic events. We propose to test these hypotheses by performing cross-sectional study on 14,000 participants in a longitudinal study of Atherosclerosis Risk Communities (ARIC) to determine the contribution of periodontal infection variables to existing multivariate models of atherosclerosis. Using a cross-sectional design we will measure periodontal disease variables including periodontal probing depths and clinical attachment levels. Plaque samples will be collected for storage and later quantitation of Porphyromonas gingivalis, as S. Sanguis. Gingival crevicular fluid will be collected for the quantitation of Prostaglandin E2 (PGE2) thromboxane B2 (TxB2), Interleukin-1B (IL-1B) and tumors necrosis factor a (TNFa). Serum sample will be analyzed for whole-cell and LPS-specific antibody titers against selected periodontal pathogens. These measures will be sued to test associations with clinical measures of heart disease, heart attack, death from heart disease, and direct ultrasound measures of carotid and popliteal intima-media thickening and lesions as well as atherogenic risk factors that continue to be gathered in the ARIC Study. More specifically, we will determine whether the local gingival crevicular fluid levels of TxB2, IL-1B, TNFa and PGE2 are elevated in cases of severe atherosclerotic stenosis and whether elevated levels of these mediators are associated with other atherosclerosis risk factor including elevated serum lipid variables, serum TxB2 and fibrinogen.
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