This project will prepare the candidate, Dr. Aruna Pradhan, for a career as an independent clinical scientist in cardiovascular epidemiology with a focus on risk assessment of peripheral arterial disease (PAD), her area of scientific interest. At the time of award activation, Dr. Pradhan will be a board eligible cardiologist having completed her fellowship training at the Brigham and Women's Hospital (BWH), Boston. Her post-doctoral research activities have been undertaken in the Center for Cardiovascular Disease Prevention within the Division of Preventive Medicine, BWH. The Center provides a scientifically productive environment for the support of junior investigators in the conduct of population-based epidemiologic research. The applicant proposes a 5-year program of research that will prospectively evaluate novel and traditional risk factors for PAD in women, among whom limited epidemiologic data exist. The risk factors to be examined may be categorized into one of three groups: novel biomarkers, traditional and behavioral cardiovascular risk factors, and dietary influences. Employing a prospective cohort design, analyses will be conducted in the Women's Health Study of 39,876 healthy middle-aged American women. The long-term follow-up and high- quality covariate data in this cohort offer a unique opportunity to study, in a prospective manner, potentially modifiable risk factors for PAD in a large well-characterized population of women. At the conclusion of the award period, Dr. Pradhan will have acquired advanced epidemiologic skills and expertise in the study of PAD which will enable her to independently conduct research in prevention and treatment of this disease. This proposal seeks to evaluate the association between a broad range of emerging and traditional risk factors and the development of atherosclerosis in the lower extremity arterial system among American women. While prior limited data are available pertaining to these risk factors in men, information with regard to risk factor relationships in women are extremely sparse. Specific exposures of interest include blood- based biomarkers, traditional cardiovascular risk factors such as diabetes, obesity, and elevated blood pressure, behavioral risk factors such as smoking and physical inactivity, and dietary influences such as fat, antioxidant, and carbohydrate intake.