ORAL MICROBES AND CARDIOVASCULAR DISEASE

本研究旨在探讨口腔感染对心血管疾病（包括动脉粥样硬化、冠心病、中风和心肌梗死）发病率和死亡率的影响。基于过去二十年来社区心血管风险前瞻性研究的最新报告数据表明，即使在控制了广泛的传统心血管风险因素，如血清甘油三酯、胆固醇、体重、血压和吸烟后，流行的口腔感染，特别是牙周炎，是致死性冠心病和中风的重要危险因素（优势比为1.9-2.8）。这种关联的潜在机制尚不清楚，这是本研究的重点。具体而言，我们要求支持测量针对特定口腔微生物病原体的血清抗体滴度，并定量这些微生物在口腔龈下菌斑样本中的水平，这些样本来自先前的14,000名学生，以确定特定牙周病原体或全身暴露的存在或水平是否与心血管疾病相关。这将是一项有心血管疾病（病例）或无心血管疾病（对照组）的牙周炎患者的病例对照研究。预计将对1100名牙周炎患者进行分析，其中200-300人为病例。我们将验证4种关键病原体（牙龈卟啉单胞菌、连翘拟杆菌、齿状密螺旋体和放线菌杆菌）与冠心病病例状态显著相关的假设。我们还将筛选电池或口腔微生物，包括已知会诱导血小板聚集的链球菌，以确定是否与病例状态相关的其他微生物。因此，我们提出这一申请，请求支持，使我们能够从经典传染病的角度确定特定的牙周病原体是否与冠心病有关，在心血管危险因素和潜在混杂因素的前所未有的全面补充下。

This proposal seeks to examine the contribution of oral infection to the morbidity and mortality of cardiovascular disease include atherosclerosis, coronary heart disease (CHD), stroke and myocardial infarction. Newly reported data based upon prospective studies of cardiovascular risk in communities conducted over the last two decades have indicated that prevalent oral infections, and especially periodontitis, are significant risk factors for fatal CHD, and stroke (odds ratio 1.9-2.8), even after controlling for an extensive array of traditional cardiovascular risk factors, such as serum triglyceride, cholesterol, body mass, blood pressure and smoking. The underlying mechanism for this association is unknown and represents the key focus of this proposed investigation. Specifically, we request support to measure serum antibody titers to specific oral microbial pathogens and quantitate the levels of these microbes in oral subgingival plaque samples, collected from a previously characterized population of 14,000 students, to establish whether the presence or levels of specific periodontal pathogens or systemic exposure are associated with cardiovascular disease. This will be a case-control study of subjects with periodontitis who have cardiovascular disease (cases) or no cardiovascular disease (controls). Analyses will be performed on an estimated 1100 periodontitis patients of which 200-300 will be cases. We will test the hypothesis that 4 key pathogens (Porphyromonas gingival, Bacteroides forsythus, Treponema denticola and Actinobacillus actinomycetemcomitans) are significantly associated with CHD case status. We will also screen against a battery or oral organisms including Streptococcus species, known to induce platelet aggregation, to determine whether other microbes are associated with case status. Thus, we are bringing this application forward to request support to enable us to determine from a classic infectious disease standpoint whether specific periodontal pathogens are associated with CHD, in the presence of an unprecedented full complement of cardiovascular risk factors and potential confounders.