This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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