ORAL MICROBES AND CARDIOVASCULAR DISEASE

这项建议旨在研究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。基于过去二十年在社区进行的心血管风险前瞻性研究的新报告数据表明，流行的口腔感染，特别是牙周炎，是致死性CHD和中风的重要危险因素（比值比1.9-2.8），即使在控制了广泛的传统心血管危险因素，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，这是本研究的重点。具体来说，我们要求支持测量血清抗体滴度，以特定的口腔微生物病原体和定量的水平，这些微生物在口腔龈下菌斑样本，收集从先前的特征人口的14,000名学生，以确定是否存在或特定的牙周病原体或全身暴露水平与心血管疾病。这将是一项病例对照研究，受试者为患有心血管疾病（病例）或无心血管疾病（对照）的牙周炎受试者。分析将在估计的1100名牙周炎患者中进行，其中200-300例将是病例。我们将检验4种主要病原体（牙龈卟啉单胞菌、类杆菌、齿垢密螺旋体和伴放线放线杆菌）与CHD病例状态显著相关的假设。我们还将对电池或口腔微生物进行筛查，包括已知可诱导血小板聚集的链球菌属，以确定其他微生物是否与病例状态相关。因此，我们提出了这项申请，要求支持，使我们能够确定从一个经典的传染病的角度来看，是否特定的牙周病原体与冠心病，在一个前所未有的全面心血管危险因素和潜在的混杂因素的存在。

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.