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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。感染是冠心病（CHD）的一个新兴危险因素，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累和由此产生的牙龈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，从而有助于我们理解冠心病风险的差异。这些反应可能受性别或种族的支配。拟议的研究将是第一个使用这种方法解决这些问题的研究。核心假设是，牙菌斑的积累会产生全身性的后果，有可能增加冠心病的风险。实验牙龈炎模型将成为本研究的核心。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，并在刺激退出时解决。该研究将在至少100名健康的年轻成人受试者（男女人数相等，黑人和白人）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，个人将进行细致的斑块控制；2) 21天的实验阶段，在此期间，受试者将不采取任何口腔卫生措施；3) 21天恢复期，在此期间恢复口腔卫生措施。在这些阶段，牙菌斑和牙龈炎的水平将被评估。外周血采集将允许同时评估与冠心病风险增加相关的全身因素（炎症标志物水平、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，通过比较研究期间特定日期收集的临床和实验室数据，每个受试者将作为自己的对照。此外，分析将允许识别高反应和低反应，即对给定的局部细菌攻击分别表现出显着增加或减少炎症反应的个体。还将讨论性别和种族在多大程度上影响这一点。本研究结果将进一步了解口腔疾病在增加冠心病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.