ORAL MICROBES AND CARDIOVASCULAR DISEASE

这项建议旨在研究口腔感染对动脉粥样硬化、冠心病(CHD)、中风和心肌梗死等心血管疾病的发病率和死亡率的影响。基于过去20年进行的社区心血管风险前瞻性研究的最新报告数据表明，流行的口腔感染，特别是牙周炎，是致命的冠心病和中风的重要风险因素(优势比1.9-2.8)，即使在控制了一系列传统的心血管风险因素后，如血清甘油三酯、胆固醇、体重、血压和吸烟。这种关联的潜在机制尚不清楚，并代表了这项拟议调查的关键重点。具体地说，我们要求支持测量特定口腔微生物病原体的血清抗体效价，并量化从先前确定的14,000名学生人口中收集的口腔牙周菌斑样本中这些微生物的水平，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有关。这将是一项病例对照研究，研究对象为患有心血管疾病的牙周炎受试者(病例)或无心血管疾病的受试者(对照)。将对大约1100名牙周炎患者进行分析，其中200-300人将是病例。我们将检验4种主要病原体(牙龈卟啉单胞菌、福赛斯类杆菌、齿密螺旋体和伴生放线杆菌)与冠心病病例状态显著相关的假设。我们还将筛选包括链球菌在内的已知可诱导血小板聚集的口腔微生物，以确定其他微生物是否与病例状态有关。因此，我们提出这项申请是为了请求支持，使我们能够在存在前所未有的心血管危险因素和潜在混杂因素的情况下，从经典传染病的角度确定特定的牙周病原体是否与CHD有关。

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.