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Background and Objective Matrix metalloproteinase-8 ( MMP-8) is involved in a wide range of pathologies including periodontitis and cardiovascular diseases ( CVD). The association between periodontitis and CVD has been repeatedly recognized. The aim of the study was to analyze to what extent circulating active MMP-8 ( aMMP-8) is associated with periodontal disease status and oral fluid aMMP-8 levels in otherwise healthy subjects. Material and Methods In a cross-sectional study, aMMP-8 was measured in serum of 59 volunteers, comprising 19 periodontally healthy subjects, 20 patients with gingivitis as well as 20 with periodontitis. All study subjects were characterized regarding aMMP-8 concentrations in different oral fluids as well as clinically and microbiologically with respect to periodontal disease. aMMP-8 levels in gingival crevicular fluid were measured using the enzyme-linked immunosorbent assay. Saliva enzyme levels as well as circulating aMMP-8 were determined by a time-resolved immunofluorometric assay. Both methods utilized the same monoclonal antibodies. Correlation and regression analyses were performed to study the potential association between serum aMMP-8 and oral parameters. Results Oral aMMP-8 levels were significantly higher in patients with periodontitis compared to periodontally healthy or gingivitis subjects. Highest serum aMMP-8 concentration was also found in the periodontitis group. The serum levels correlated significantly with oral aMMP-8 as well as with clinical parameters in a dose-dependent manner. These results were confirmed in a multivariate regression analysis. After adjusting for potential confounders, saliva aMMP-8 concentrations as well as periodontitis severity were significant predictors of serum aMMP-8. Conclusion The associations between circulating aMMP-8 and oral aMMP-8 as well as periodontal findings in a dose-dependent manner may contribute to linking periodontal disease with increased CVDsusceptibility. [ABSTRACT FROM AUTHOR]