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

基本信息

批准号：
7480291
负责人：
FRANCINE K WELTY
金额：
$ 42.1万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/7480291
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

项目摘要

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（由适用提供）：该提案的总体目的是确定牙周疾病作为冠心病和代谢综合征受试者的感染性和炎症暴露的贡献，对非估计（软）和钙化冠状斑块的患病和进展。牙周疾病将通过临床检查，局部炎症标志物的水平（在牙龈5术液），层次的口服生物膜生物以及900名受试者的细菌IgG抗体的水平，具有冠心病的900名受试者的特定于血清IgG抗体，并在临床上综合研究中的父母专科综合体中注入了临床综合综合体中心（SCCCOR）综合综合体中的代谢综合症中心贝丝以色列执事医疗中心的血管重塑”。 Welty博士是该血管损伤，维修和改建SCCOR的首席研究员兼董事，该血管损伤已经获得资金。在这项研究中，有900名患有冠状动脉疾病和代谢综合征的受试者将被随机分为3臂之一：萨拉酸酯（一种减少感染和血糖的药物），强化生活方式的变化适合减肥或通常的护理（安慰剂）30个月。这些受试者将经历多探测器计算的层析成像造影术，以评估冠状动脉中未估计的斑块的程度，并具有炎症，氧化应激和胰岛素灵敏度的血清标记，并在基线和30个月的随访中测得。 C反应性蛋白和血清淀粉样蛋白A（急性相反应物），细胞因子（IL-6，TNFA，IL-1？），脂质，胰岛素敏感性的测量（葡萄糖，HGBA1C，禁食胰岛素和稳态的胰岛素模型），胰岛素抵抗的模型，胰岛素抗性），胰岛素抗性9群nfrix nfrix？（纤溶酶原激活物抑制剂1 [PAI-1]和纤维蛋白原）]和粘合分子（VCAM-1和ICAM-1）也将在基线和30个月的随访（由父型SCCOR GRANT资助）下进行测量。当前牙科提案的总体目的是：1）描述临床牙周疾病的患病率，程度和严重程度，口服细菌负荷水平，细菌特异性血清IgG反应以及局部（GCF）的水平（GCF）和全身性炎症标志物以及非估计（软）和钙化的斑块之间的关联； 2）为了确定受试者是否随机化为水杨酸盐，一种抑制NF？b的药物，降低血浆葡萄糖并改善胰岛素抵抗，与安慰剂在随访时相比具有更好的口服和心血管健康。 3）确定与安慰剂在随访时相比，与安慰剂相比，对随机变化的受试者的口服和心血管健康是否更好； 4）确定生物膜生物，血清抗体水平和NF？b激活之间的关联； 5）。确定牙周疾病与血糖控制在冠心病的发育和进展中的关联； 6）确定冠心病和代谢综合征中牙周疾病的患病率和发病率或进展率的预测因素。这项研究可能会导致重要的公共卫生信息。如果该项目表明牙周疾病与冠状动脉斑块的发展有关，那么公众将受益于更具侵略性的口腔保健。这项研究还可能表明乳豆人可以改善口腔和牙周健康。