Periodontal Disease and Coronary Artery Remodeling in CHD and Metabolic Syndrome

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DESCRIPTION (provided by applicant): The overall objective of this proposal is to determine the contribution of periodontal disease as an infectious and inflammatory exposure in subjects with coronary heart disease and metabolic syndrome to the prevalence and progression of both non-calcified (soft) and calcified coronary plaque. Periodontal disease will be assessed by clinical exam, levels of local inflammatory markers (within gingival crevicular fluid), levels of subgingival oral biofilm organisms as well as bacterial specific serum IgG antibody in 900 subjects with coronary heart disease and metabolic syndrome enrolled in the parent Specialized Center of Clinically Oriented Research (SCCOR) clinical trial "Metabolic Syndrome, Inflammation and Vascular Remodeling", at Beth Israel Deaconess Medical Center. Dr. Welty is the Principal Investigator and Director of this Vascular Injury, Repair and Remodeling SCCOR, which has already been funded. In this study, 900 subjects with coronary heart disease and metabolic syndrome will be randomized to one of 3 arms: Salsalate (a drug that reduces inflammation and blood glucose), intensive lifestyle changes geared toward weight loss or usual care (placebo) for 30 months. These subjects will undergo multidetector computed tomographic angiography to assess extent of non-calcified plaque in the coronary arteries and have serum markers of inflammation, oxidative stress and insulin sensitivity measured at baseline and at 30 month follow-up. C-reactive protein and serum amyloid A (acute phase reactants), cytokines (IL-6, TNFa, IL-1¿), lipids, measures of insulin sensitivity (glucose, HgBA1c, fasting insulin and homeostasis model assessment of insulin resistance), activation of NF?B in plasma, matrix metalloproteinase 9, thrombotic factors (plasminogen activator inhibitor-1[PAI-1] and fibrinogen)] and adhesion molecules (VCAM-1 and ICAM-1) will also be measured at baseline and 30-month follow-up (funded by parent SCCOR grant). The overall aims of the current dental proposal are: 1) To describe the association between prevalence, extent and severity of clinical periodontal disease, level of oral bacterial load, the bacterial-specific serum IgG response, and the levels of local (GCF) and systemic inflammatory markers and both non-calcified (soft) and calcified plaque; 2) To determine if subjects randomized to salicylate, a drug which inhibits NF?B, lowers plasma glucose and improves insulin resistance, have better oral and cardiovascular health compared to placebo at follow-up; 3) To determine if subjects randomized to intensive lifestyle changes have better oral and cardiovascular health compared to placebo at follow-up; 4) To determine the association between biofilm organisms, serum antibody level and activation of NF?B; 5). To determine the association between periodontal disease and glycemic control in development and progression of CHD; and 6) To determine predictors of the prevalence and incidence or progression rates of periodontal disease in CHD and metabolic syndrome. Important public health information may result from this study. If this project shows that periodontal disease is related to the progression of coronary plaque, the public would benefit by more aggressive oral health care. This study may also show that salsalate improves oral and periodontal health.