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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 感染是冠心病（CHD）的一个新的危险因素，是美国和全球发病率和死亡率的主要原因。口腔疾病越来越多地与这种能力有关。本研究将采用急性疾病模型来确定牙菌斑积聚和由此产生的牙龈炎是否具有全身性后果，可能增加CHD的风险。此外，个体之间局部和全身反应的任何变化都将使用该模型进行识别，从而有助于我们理解CHD风险的差异。这些反应可能受性别或种族的影响。 拟议的研究将是第一次使用这种方法来解决这些问题。中心假设是牙菌斑积累会产生全身性后果，有可能增加CHD风险。 实验牙龈炎模型将形成本研究的中心核心。它允许高水平的实验控制，因为炎症响应于局部细菌挑战而发展，并且在刺激物撤回后消退。本研究将在至少100例健康年轻成人受试者（男性和女性、黑人和白色受试者数量相等）的参与下进行。它将分为三个阶段：1）21天的控制阶段，在此期间，个人将进行细致的牙菌斑控制; 2）21天的实验阶段，在此期间，个人将放弃所有口腔卫生措施; 3）21天的恢复阶段，在此期间，口腔卫生措施将恢复。在这些阶段，将评估牙菌斑和由此产生的牙龈炎的水平。外周血采集将允许同时评估据称与CHD风险增加相关的全身因素（炎症标志物、脂质代谢标志物、止血因子和内毒素水平以及中性粒细胞活化程度）。研究设计是纵向的，因此每例受试者将通过比较整个研究期间特定日期收集的临床和实验室数据作为自己的对照。此外，分析将允许鉴定高应答者和低应答者，即对给定的局部细菌攻击分别表现出显著增加或降低的炎症应答的个体。还将讨论性别和种族在多大程度上影响这一点。 本研究的结果将进一步了解口腔疾病在增加CHD风险中的潜在机制作用。

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.