The overall Aim of the application is to continue follow-up and evaluation of a randomly selected tri-ethnic cohort (n=1,056) in Northern Manhattan to determine and quantify the independent contribution of periodontal infections to vascular events and atherosclerosis. In the first 3 years of this study we have found that periodontal disease is cross-sectionally associated with carotid intima media thickness (IMT). We have further reported that bacteria admitted as causally related to periodontal disease are positively related to IMT, while those associated with periodontal health are unrelated. Preliminary 3-year prospective findings in the first % of the cohort also suggest that periodontal bacteria relate to progression of carotid IMT and incident vascular events, after adjustment for conventional risk factors. In view of these very promising findings, it is crucial to continue to follow the enrolled subjects to: a) verify that the trends seen in IMT progression at year 3 are not due to chance; and b) ensure adequate power to evaluate whether these changes translate into clinical events (strokes, heart attacks and vascular deaths). Through the joint efforts of our multi-disciplinary team, we will repeat at year 6 the extensive measurements of cardiovascular risk factors, including carotid IMT (using high resolution B-mode Doppler), and the extensive periodontal examination including clinical, microbiologic (species specific DMA probes), immunologic (species specific antibodies to periodontal bacteria), and inflammatory (GCF cytokine and systemic C-reactive protein and fibrinogen) parameters. All subjects will be re-interviewed every year. Those who report a change in their clinical status suggestive of an outcome event in the period preceding or following the in-person year 6 appointments will be brought in for evaluation. All deaths will be thoroughly investigated. By the completion of our application, subjects will have had 3 time points of extensive clinical, microbiologic, immunologic and ultrasonographic longitudinal evaluation (at years 0, 3, 6) with a followup of 6 years for IMT progression measurements and a median followup of 9 years (range 7-11 years) for the incidence of clinical events. This extensively studied and methodologically robust cohort provides a unique opportunity to answer the question of the contribution of chronic periodontal infections to vascular disease. The accurate determination and quantification of this potential risk is significant for public health, Dentistry and medicine. [unreadable] [unreadable]