Periodontal disease has been reported to be associated with cardiovascular disease (CVD), although the underlying nature of this association remains to be determined. A susceptibility to both of these diseases may be the result of the host's response to the presence of periodontal pathogens. Objectives: This project involving a CVD cohort explored the association between changes in periodontal status and the natural history of P. gingivalis and T. forsythensis over a 2-year period. Methods: Subgingival plaque was collected at baseline and then annually for 2 years from 375 subjects. Real-time PCR was used for quantification of the bacterial load. Changes in periodontal status were determined by changes in mean probing pocket depth (PPD). Differences in mean PPD between groups of subjects acquiring or losing bacteria were examined using independent t-tests and ANOVA. Results: P.g and T.f were detected in most of subjects at baseline (89.6% and 82.4% respectively). Subsequent acquisition or loss of bacteria (gain or loss of at least the baseline median level of P.g or T.f - 105 and 106 cells/mg protein respectively) was noticeably volatile. For over 50% of subjects, a gain (or loss) of either bacterium from baseline to year1 was followed by a loss (or gain) of that same bacterium from year1 to year 2. Acquisition (or loss) of P.g was directly associated with an increase (or decrease) in mean PPD (p=0.08). This trend was not affected by concurrent acquisition or loss of T.f even though the numbers of bacteria gained or lost were higher for T.f than for P.g. Conclusion: In this CVD group changes in periodontal pocket depth were primarily associated with concurrent changes in the numbers of P. gingivalis.