The central hypothesis of this application is 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. Further, 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. In addition, it is suggested that periodontal diseases, once established, provide a biological burden of endotoxin (LPS, lipopolysaccharide) and inflammatory cytokines (especially thromboxane B2 [TxB2], interleukin-1 beta [Il-1b], prostaglandin E2 [PGE2] and tumor necrosis factor alpha [TNFa]) which serve to initiate and exacerbate atherogenesis and thromboembolic events. These hypotheses will be tested by performing a cross-sectional study on 14,000 participants in a longitudinal study of Atherosclerosis Risk in Communities (ARIC) to determine the contribution of periodontal infection variables to existing multivariate models of atherosclerosis. Using a cross-sectional design, periodontal disease variables will be measured including periodontal probing depths and clinical attachment levels. Plaque samples will be collected for storage and later quantitation of Porphyromonas gingivalis and Streptococcus sanguis. Gingival crevicular fluid will be collected for the quantitation of PGE2, TxB2, IL-1 beta and TNFa. Serum samples will be analyzed for whole cell and LPS-specific antibody titers against selected periodontal pathogens. These measures will be used 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, it will be determined 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 factors including elevated serum lipid variables, serum TxB2 and fibrinogen.
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