This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposed pilot trial will be developed involving five enrollment centers and approximately 225 patients with heart disease and significant periodontal disease. The purposes of this project are as follows: 1. To design a definitive trial to understand the question of whether or not periodontal therapy will have effects on heart disease. 2. To perform a definitive clinical trial of periodontal treatment in the secondary prevention of cardiovascular events. After screening, eligible patients will be randomized to a treatment or control group after extraction of hopeless teeth and their replacement if necessary. The randomly assigned groups will be as follows: 1. Group A (Local Periodontal Therapy): Scaling and root planing plus topical, slow release doxycycline applied subgingically, and placebo tablets given once a week for three months. 2. Group B (Local Periodontal Therapy + Systemic Azithromycin): Local periodontal treatment with definitive scaling and root planing plus topical, slow release doxycycline applied subgingivally, and in addition, systemic azithromycin, one 600 mg tablets to take once a week for three months. The duration of this project is three years and approximately 225 patients will be enrolled in these treatment groups (~75 patients per group) at the end of the three years. At the time of the baseline oral examination, the eligible patients will complete a detailed questionnaire regarding demographic information, medical history, medication use, lifetime physical activity, diet history and health status information. In addition, a detailed Cardiovascular History Questionnaire will be completed. All the patients will have a complete oral examination including a standard set of periapical and bite-wing dental radiographs. Microbiological (plaque), gingival crevicular fluid, saliva and blood samples will be collected for laboratory analysis. Clinical measurements including clinical attachment level, gingival assessment, dental plaque assessment, calculus index, probing depth will be recorded. Following the treatments, all the patients will be recalled every 6 months through the study for the clinical exam and cardiovascular endpoint injury and assessment if necessary. Participants will be also called in the intervening three months to be interviewed using a standard set of questions to assess any cardiac events or adverse events, which may be important.