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：
8104174
负责人：
FRANCINE K WELTY
金额：
$ 41.08万
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 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8104174
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 Cell Adhesion Molecules Cessation of life Clinical Clinical Trials Congestive Heart Failure Coronary Coronary Circulation Coronary artery Coronary heart disease DNA Databases Dental Deposition Development Diabetes Mellitus Diet Disease Doctor of Philosophy Enrollment Fasting Fibrinogen Funding Future Gelatinase B Genetic Gingival Crevicular Fluid Glucose Glycosylated hemoglobin A Goals Grant Health Healthcare Hemorrhage Hepatic Homeostasis IL6 gene Imaging Techniques Immunoglobulin G Incidence Inflammation Inflammation Mediators Inflammatory Insulin Insulin Resistance Intercellular adhesion molecule 1 Interleukin-6 Intervention Israel Life Style Lipids Liver Measures Medical center Messenger RNA Metabolic syndrome Microbial Biofilms Modeling Myocardial Infarction NF-kappa B National Heart, Lung, and Blood Institute Nitric Oxide Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Operative Surgical Procedures Oral Oral health Organism 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 Research Research Personnel Research Project Grants Risk Risk Factors Route Salicylic Acids Sampling Serum Serum Markers Serum amyloid A protein Severities Site Smoking Specialized Center Specimen Study Subject TNF gene Testing Therapeutic Triad Acrylic Resin Variant Vascular Cell Adhesion Molecule-1 Vascular remodeling adiponectin arm blood glucose regulation cytokine dimer disorder control follow-up glycemic control heart disease risk improved indexing inflammatory marker injury and repair insulin sensitivity intercellular cell adhesion molecule isoprostaglandin F2alpha type-III lifestyle intervention microbial minimally invasive non-smoker non-smoking nonalcoholic steatohepatitis oral biofilm primary outcome programs research study response salicylate salicylsalicylic acid secondary outcome success treatment as usual

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（由申请人提供）：本提案的总体目标是确定患有冠心病和代谢综合征的受试者中牙周病作为一种感染性和炎症性暴露对非钙化（软）和牙周病的患病率和进展的贡献。牙周病将通过临床检查、局部炎症标记物（龈沟液内）水平、龈下口腔生物膜生物水平以及细菌特异性血清 IgG 抗体进行评估。患有冠心病和代谢综合征的受试者参加了贝斯以色列女执事医疗中心的临床研究专门中心 (SCCOR) 临床试验“代谢综合征、炎症和血管重塑”，Welty 博士是该试验的首席研究员和主任。这项血管损伤、修复和重塑 SCCOR 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配到其中一项。 3 组：水杨酸（一种减少炎症和血糖的药物）、针对减肥或常规护理（安慰剂）的强化生活方式改变，持续 30 个月。这些受试者将接受多探测器计算机断层血管造影，以评估非钙化斑块的程度。冠状动脉，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和血清淀粉样蛋白 A（急性期反应物）、细胞因子。（IL-6、TNFa、IL-1¿ ）、血脂、胰岛素敏感性测量（血糖、HgBA1c、空腹胰岛素和胰岛素抵抗的稳态模型评估）、血浆中 NF?B 的激活、基质金属蛋白酶 9、血栓形成因子（纤溶酶原激活剂抑制剂-1[PAI-1] 和纤维蛋白原）]和粘附分子（VCAM-1 和 ICAM-1）也将在基线和 30 个月随访时进行测量（由母公司 SCCOR 资助）当前牙科提案的总体目标是：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 反应以及局部 ( GCF）和全身炎症标志物以及非钙化（软）和钙化斑块；2) 确定随机服用水杨酸盐（一种抑制 NF?B、降低血浆葡萄糖并改善胰岛素抵抗的药物）的受试者是否有更好的口腔和心血管健康比较的随访时给予安慰剂；3) 与安慰剂相比，随机接受强化抗体生活方式改变的受试者在随访时是否有更好的口腔和心血管健康；4) 确定生物膜生物、血清水平和 NF 激活之间的关系？ B; 5). 确定牙周病与冠心病发生和进展中的血糖控制之间的关系；以及 6) 确定冠心病和代谢综合征中牙周病的患病率和发病率或进展率的预测因素。由此产生的结果如果该项目表明牙周病与冠状动脉斑块的进展有关，那么公众将受益于更积极的口腔保健。该研究还可能表明双水杨酸可以改善口腔和牙周健康。