Abstract Body: Periodontal disease, specifically periodontitis, is a progressive multidimensional inflammatory disease of the oral cavity. In addition to adverse oral health consequences, periodontitis is associated with increased risk of atherothrombotic cardiovascular disease and events. Importantly, periodontitis affects >40% of adults in the United States over the age of 30 years. Despite improved management of many of the oral health consequences associated with periodontitis, factors that initiate and promote increased atherothrombotic risk and events are poorly understood. Elevated levels of circulating soluble cell adhesion molecules and fibrin D-dimer are markers of a proatherogenic vascular environment and strong prognostic indicators of atherothrombotic events. We tested the hypothesis that circulating levels of soluble cell adhesion molecules and fibrin D-dimer are elevated in adults with periodontitis, which, in turn, may contribute to the heightened risk of vascular disease and events in this population. Peripheral blood was collected from 26 middle-aged adults: 13 without periodontitis (9 M/4F; age: 49+3 yr; BMI: 28.5+0.9 kg/m²) and 13 clinically diagnosed with periodontitis (7 M/6 F; 54+4 yr; 26.0+1.6 kg/m²). All subjects were free of overt cardiovascular and metabolic disease. Plasma concentrations of extracellular soluble adhesion molecules (intracellular adhesion molecule-1 [sICAM-1], vascular adhesion molecule-1 [sVCAM-1], platelet endothelial cell adhesion molecule-1 [sPECAM-1] and E-selectin) and fibrin D-dimer were determined by immunoassay. sICAM-1 (265±14 vs 218±11 ng/mL), E-selectin (48±4 vs 36±3 ng/mL) and fibrin D-dimer (408±47 vs 278±31 ng/mL) were significantly higher (~25-50%) in adults with periodontitis. There were no significant group differences in either sVCAM-1 (595±38 vs 596±53 ng/mL) or sPECAM-1 (10±1 vs 9±1 ng/mL). Elevated circulating levels of sICAM and sE-selectin are sensitive biomarkers of vascular endothelial cell activation and adhesion and have been linked with increased risk of atherogenesis; in addition, elevated fibrin D-dimer is a direct indicator of thrombotic activity. Thus, the increased risk and prevalence of atherothrombotic events in adults with periodontitis may be mediated, in part, by increased expression of cell adhesion molecules and a prothrombotic environment as indicated by elevated soluble cell adhesion molecules and fibrin D-dimer levels.