DENTAL PLAQUE ACCUMULATION AS A RISK FACTOR FOR CHD (#04-G-011)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 感染是冠心病(CHD)的一个新的危险因素，冠心病是美国和世界范围内发病率和死亡率的主要原因。口腔疾病越来越多地牵涉到这种能力。这项研究将采用急性疾病模型来确定牙菌斑堆积和由此引起的牙周炎是否具有增加冠心病风险的全身性后果。此外，使用该模型可以识别个体之间局部和全身反应的任何差异，从而有助于我们了解冠心病风险的差异。这些反应可能会受到性别或种族的影响。拟议的研究将是第一个使用这种方法处理这些问题的研究。中心假设是，牙菌斑堆积将产生全身性后果，有可能增加CHD风险。 实验性牙周炎模型将构成这项研究的中心核心。它允许高水平的实验控制，因为炎症是对局部细菌挑战的反应，并在退出刺激时消失。这项研究将由至少100名健康的青年受试者参与(男女人数相等，黑人和白人人数相等)。计划将分为三个阶段：1)为期21天的控制期，在此期间，个别人士会进行细致的菌斑控制；2)为期21天的试验阶段，在此期间，个别人士将不再采取所有口腔卫生措施；及3)为期21天的恢复期，期间将恢复口腔卫生措施。在这些阶段中，将评估牙菌斑和由此导致的牙龈炎的水平。采集外周血液将允许同时评估据称与冠心病风险增加相关的全身因素(炎症标志物、脂代谢标志物、止血因子和内毒素的水平，以及中性粒细胞激活的程度)。研究设计是纵向的，这样每个受试者将通过比较在整个研究期间特定日期收集的临床和实验室数据作为他们自己的对照。此外，分析将允许识别高反应者和低反应者，即对给定的局部细菌挑战分别表现出显著增强或降低的炎症反应的个体。性别和种族对这一问题的影响程度也将得到解决。 这项研究的结果将进一步了解口腔疾病在增加冠心病风险方面的潜在机制作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Infection is an emerging risk factor for coronary heart disease (CHD), the major cause of morbidity and mortality in the US and worldwide. Oral disease is increasingly implicated in this capacity. This study will employ an acute disease model to determine whether dental plaque accumulation and the resultant gingivitis have systemic consequences with the potential to increase risk for CHD. Moreover, any variation in both the local and systemic responses between individuals will be identified using this model, thus contributing to our understanding of disparity in CHD risk. These responses may be governed by gender or race. The proposed study will be the first to address these issues using such methodology. The central hypothesis is that dental plaque accumulation will have systemic consequences, with the potential for increasing CHD risk. The experimental gingivitis model will form the central core of this study. It permits a high level of experimental control, as inflammation develops in response to a localized bacterial challenge, and resolves upon withdrawal of the stimulus. The study will be conducted with the participation of a minimum of 100 healthy young adult subjects (equal numbers of male and female, and black and white). It will be divided into three phases: 1) The 21-day Control phase, during which individuals will perform meticulous plaque control; 2) the 21-day Experimental phase, during which individuals will abstain from all oral hygiene measures; and 3) the 21-day Recovery phase, during which oral hygiene measures will be re-instated. Throughout these phases, levels of dental plaque and resultant gingivitis will be assessed. Peripheral blood collection will permit the concomitant assessment of systemic elements purported to be associated with increased CHD risk (levels of inflammatory markers, markers of lipid metabolism, hemostatic factors and endotoxin, and the extent of neutrophil activation). The study design is longitudinal, and such that each subject will serve as their own control through the comparison of clinical and laboratory data collected on specific days throughout the study period. Furthermore, analysis will permit the identification of high- and low-responders, that is individuals exhibiting a significantly increased or decreased inflammatory response respectively, to a given local bacterial challenge. The extent to which gender and race influence this will also be addressed. The results of this study will further understanding of the potential mechanistic role of oral disease in increasing CHD risk.