This is a competing continuation of a K 24 award from the candidate who is an Associate Professor of Medicine at Boston University School of Medicine (BUSM), and a senior clinical investigator at the Framingham Heart Study (FHS). His training in cardiology and epidemiology, mentoring and program development skills, and excellent track record in conducting and mentoring clinical research render him a suitable candidate for this research career award. During the award period, the candidate will continue to spend 40% effort on the research outlined below (including mentoring), 45% effort on his other research support, and 15% on clinical work. His long-term career objectives are to work as a clinical investigator building on the research theme of investigating biomarkers of preclinical heart failure, genetic and environmental correlates of ventricular remodeling, epidemiology of vascular dysfunction (endothelial dysfunction and conduit artery stiffness) and abnormal ventriculo-vascular coupling (and relations to heart failure risk), and to mentor young clinical investigators. The interdisciplinary research group, the high-quality research infrastructure, the opportunities for mentoring, and the support of senior colleagues render the FHS and BUSM ideal settings for the candidate's pursuit of his career as a clinical investigator. The current proposal investigates the role of aldosterone in mediating vascular dysfunction and has the following specific aims: 1. To assess the clinical, inflammatory and genetic correlates of serum aldosterone. 2. To perform cross-sectional analyses on the relations of serum aldosterone to carotid intimal medial thickness, and to dynamic measures of central conduit artery function. 3. To perform cross-sectional analyses on the relations of serum aldosterone to select measures of brachial arterial endothelial function; and to microalbuminuria. 4. To describe the relations of serum aldosterone prospectively to incident CVD events The proposed K 24 award will allow the candidate and his mentees to focus on the vascular biology of aldosterone and its relations to vascular dysfunction and risk over the next five years, and will provide the candidate an opportunity for nurturing the next generation of patient-oriented researchers. The mentorship plan consists of mentoring the research of and teaching a module on clinical research design to fellows at the FHS and BUSM and will contribute directly to the growth and development of young clinical investigators at these institutions. Activities for career development of the candidate are also planned in the areas of proteomics and genetic epidemiology.
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