Project Abstract Cardiovascular disease (CVD) claims more lives each year than cancer and chronic respiratory disease combined. Participation in cardiac rehabilitation (CR) reduces mortality and risk of a major cardiovascular event in secondary prevention populations, including older adults. Older adults are less likely to participate in CR, as comorbidities in this population, including arthritis and chronic obstructive pulmonary disease, make participation difficult. Singing is a physical activity that involves components of the vagal nerves manifested as changes in cardiac autonomic regulation. Unlike physical exercise, the effects of singing on cardiovascular health has not been well-studied. To our knowledge, no studies have evaluated the impact of singing on important cardiac biomarkers. Our hypothesis is that older patients with CVD will have favorable improvement in cardiovascular biomarkers, including, endothelial function and heart rate variability (HRV), after 30 minutes of singing. Our pilot data in 23 subjects provides proof of principle, with a small, but significant, improvement in peripheral vascular endothelial function (measured by peripheral arterial tonometry) after 10 minutes of singing. This pilot study has helped us optimize the clinical trial design for this proposal, which will include a more targeted population, incorporation of personal music preferences, increased duration of singing, inclusion of a music therapist and measurement of brachial artery flow-mediated dilation (FMD), the ?gold standard? measurement for vascular endothelial function, as our primary outcome. Our proposal seeks to create, optimize and test two different singing interventions in older patients with CVD. The study will consist of three arms, according to a randomized, single-blind, crossover, sham procedure-controlled design. Sixty-five total participants will each have three visits on three different occasions for the following interventions: (1) a 30-minute period of guided singing from an in- person music therapist, (2) a 30-minute period of singing along to an instructional video including a professor of voice and ?inexperienced, older singing student? and (3) a 30-minute rest period without any intervention. We will use biofeedback (target heart rate and BORG Rating of Perceived Exertion) to help subjects optimize the cardiovascular impact of the music interventions. The (2-year) R61 phase of this proposal will assess the feasibility (implementation, practicality, and acceptability) of executing the proposed study design (Aim 1). We anticipate that the R33 phase will take 3 years to complete. The combined R61/R33 phases will be statistically powered to assess changes in FMD and HRV (primary and secondary outcomes, Aims 2a and 2b). An alternative mechanism in Aim 3 will explore the impact of singing on mental health and well-being by measuring salivary cortisol and cytokines and by using a validated visual mood score designed to evaluate performing arts activities in healthcare settings. We will determine which singing intervention, if any, is superior to the other ? as this would be important to guide longer and larger clinical trials in the field. Knowledge gained from this proposal will improve our understanding of biologic mechanisms of singing behaviors, as it relates to CVD.