Periodontal Disease and Coronary Artery Remodeling in CHD and Metabolic Syndrome

冠心病和代谢综合征中的牙周病和冠状动脉重塑

• 批准号: 7246132
• 负责人: FRANCINE K WELTY
• 金额: $ 45万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-10 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7246132
• 关键词: 3-nitrotyrosine; Abdomen; Acute-Phase Proteins; Adipose tissue; Ancillary Study; Angiography; Angioplasty; Antibodies; Area; Arterial Fatty Streak; Blood Glucose; Blood Vessels; Body Weight decreased; Bypass; C-Peptide; C-reactive protein; Calcified; Cardiovascular system; Caring; Cell Adhesion Molecules; Cessation of life; Clinical; Clinical Trials; Congestive Heart Failure; Coronary; Coronary Circulation; Coronary artery; Coronary heart disease; Databases; Dental; Deposition; Depth; Development; Diabetes Mellitus; Diet; Disease; Disease regression; Doctor of Philosophy; End Point; Enrollment; Fasting; Fibrinogen; Funding; Future; Gelatinase B; Genetic; Gingival Crevicular Fluid; Glucose; Glycosylated hemoglobin A; Goals; Grant; Health; Hemorrhage; Hepatic; Homeostasis; IL6 gene; Imaging Techniques; Immunoglobulin G; Incidence; Inflammation; Inflammatory; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin-6; Intervention; Invasive; Israel; Life Style; Lipids; Liver; Measures; Mediator of activation protein; Medical center; Messenger RNA; Metabolic syndrome; Microbial Biofilms; Modeling; Myocardial Infarction; NF-kappa B; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Operative Surgical Procedures; Oral; Oral health; Organism; Outcome; Oxidative Stress; Parents; Participant; Pathogenesis; Pathway interactions; Patients; Periodontal Diseases; Pharmaceutical Preparations; Placebos; Plant Roots; Plasma; Plasminogen Activator Inhibitor 1; Prevalence; Principal Investigator; Process; Proteins; Public Health; Randomized; Randomized Clinical Trials; Rate; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Route; Salicylic Acid; Salicylic Acids; Sampling; Serum; Serum Markers; Serum amyloid A protein; Severities; Site; Smoking; Specialized Center; Specimen; Study Subject; Testing; Therapeutic; Triad Acrylic Resin; Upper arm; Variant; Vascular Cell Adhesion Molecule-1; Vascular remodeling; Week; adiponectin; blood glucose regulation; cytokine; dimer; follow-up; glycemic control; heart disease risk; improved; indexing; injury and repair; insulin sensitivity; intercellular cell adhesion molecule; isoprostaglandin F2alpha type-III; lifestyle intervention; microbial; non-smoker; non-smoking; nonalcoholic steatohepatitis; oral biofilm; programs; research study; response; salicylate; salicylsalicylic acid; success

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.

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性暴露对非钙化（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体水平以及细菌特异性血清IgG抗体，900名患有冠心病和代谢综合征的受试者参加了母公司临床导向研究专业中心（SCCOR）临床试验“代谢综合征、炎症和血管重塑”，贝斯以色列女执事医疗中心Welty博士是该血管损伤、修复和重塑SCCOR的主要研究者和主任，该项目已经获得资助。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配到3组之一：双水杨酸酯（一种降低炎症和血糖的药物），强化生活方式改变，以减轻体重或常规护理（安慰剂）30个月。这些受试者将接受多探测器计算机断层扫描血管造影术，以评估冠状动脉中非钙化斑块的程度，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，TNF α，IL-1？），脂质，胰岛素敏感性（葡萄糖，HgBA 1c，空腹胰岛素和胰岛素抵抗的稳态模型评估），NF？还将在基线和30个月随访时测量血浆中的B、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[派-1]和纤维蛋白原）和粘附分子（VCAM-1和ICAM-1）（由SCCOR资助）。目前牙科建议的总体目标是：1）描述临床牙周病的患病率，范围和严重程度，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接受水杨酸盐，一种抑制NF？B，降低血糖和改善胰岛素抵抗，在随访时与安慰剂相比具有更好的口腔和心血管健康; 3）确定随机分配到强化生活方式改变的受试者在随访时与安慰剂相比是否具有更好的口腔和心血管健康; 4）确定生物膜生物体、血清抗体水平和NF？B; 5）.探讨牙周病与血糖控制在冠心病发生、发展中的关系; 6）冠心病和代谢综合征患者牙周病患病率、发生率或进展率的预测因素。 本研究可能产生重要的公共卫生信息。 如果这项研究显示牙周病与冠状动脉斑块的进展有关，公众将受益于更积极的口腔保健。这项研究也可能表明双水杨酸改善口腔和牙周健康。