Periodontal Disease and Coronary Artery Remodeling in CHD and Metabolic Syndrome

描述（由申请人提供）：本提案的总体目标是确定牙周病作为冠心病和代谢综合征受试者的感染性和炎症暴露对非钙化（软）和钙化冠状动脉斑块的患病率和进展的贡献。牙周病将通过临床检查、局部炎症标志物水平（龈沟液内）、龈下口腔生物膜生物水平以及细菌特异性血清IgG抗体对900名冠心病和代谢综合征患者进行评估，这些患者参加了贝斯以色列女Deaconess医疗中心临床研究专业中心（SCCOR）的“代谢综合征、炎症和血管重塑”临床试验。Welty博士是该血管损伤、修复和重塑SCCOR的首席研究员和主任，该项目已获得资助。在这项研究中，900名患有冠心病和代谢综合征的受试者将被随机分为三组：Salsalate（一种减少炎症和血糖的药物），针对减肥的密集生活方式改变或常规护理（安慰剂），为期30个月。这些受试者将接受多探测器计算机断层血管造影，以评估冠状动脉非钙化斑块的范围，并在基线和30个月随访时测量炎症、氧化应激和胰岛素敏感性的血清标志物。c -反应蛋白和血清淀粉样蛋白A（急性期反应物）、细胞因子（IL-6、TNFa、IL-1¿）、脂质、胰岛素敏感性（葡萄糖、糖化血红蛋白、空腹胰岛素和胰岛素抵抗的稳态模型评估）、NF？血浆、基质金属蛋白酶9、血栓形成因子（纤溶酶原激活物抑制剂-1[PAI-1]和纤维蛋白原）和粘附分子（VCAM-1和ICAM-1）中的B也将在基线和30个月的随访（由母公司SCCOR资助）中进行测量。目前牙科建议的总体目标是：1)描述临床牙周病的患病率、程度和严重程度、口腔细菌负荷水平、细菌特异性血清IgG反应、局部（GCF）和全身炎症标志物水平以及非钙化（软）和钙化斑块之间的关系；2)确定受试者是否随机服用抑制NF的药物水杨酸？B，降低血糖，改善胰岛素抵抗，与安慰剂相比，在随访中有更好的口腔和心血管健康；3)在随访中确定随机接受强化生活方式改变的受试者与安慰剂相比是否有更好的口腔和心血管健康；4)确定生物膜生物、血清抗体水平与NF?B活化之间的关系；5)。探讨牙周病与血糖控制在冠心病发生发展中的关系；6)确定冠心病和代谢综合征患者牙周病患病率、发病率或进展率的预测因素。这项研究可能会提供重要的公共卫生信息。如果这个项目显示牙周病与冠状动脉斑块的发展有关，公众将受益于更积极的口腔保健。这项研究也可能表明水杨酸盐可以改善口腔和牙周健康。

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.