Mechanisms of Vascular Dysfunction in Obesity & the Metabolic Syndrome

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DESCRIPTION (provided by applicant): Candidate: During Pediatric Cardiology fellowship, I worked with Bogalusa Heart Study investigators and planned to continue a combined clinical/research career but personnel changes in my practice led to an increased clinical load frustrating my attempts to complete a Masters in Public Health. My goal of becoming an independent researcher in Pediatric CV disease epidemiology was left unfulfilled. When the chance came to join Cincinnati Children's Hospital, I embraced the challenge, eager to get my career back on track. This K23 award will be instrumental in providing me with the training I need to become an expert in Pediatric Vascular Function. Environment: Children's is the ideal environment for my transition back to a research career. My reduced clinical duties now focus on Preventive Cardiology, and I am enrolled in the Masters program at the University of Cincinnati. I have been provided up-to-date vascular equipment and numerous mentoring opportunities which have led to productive interdisciplinary relationships culminating in pilot data for 2 abstracts and in preparation of this K23 proposal. Research: Childhood obesity has increased dramatically in the U.S., and these children are at risk for target organ damage, adult diabetes, heart disease and stroke. One of the pathways by which obesity induces target organ damage may involve fat derived adiponectin's (APN) effect on vascular function. APN directly protects the vasculature and is reduced in obesity, its related inflammation and in coronary artery disease. Low levels are associated with insulin resistance and the dyslipidemia of metabolic syndrome. We propose a cross-sectional study of school-aged adolescents to study relationships between obesity and vascular function to determine if the mechanisms of dysfunction may relate to abnormal levels of CV risk factors, inflammation and APN. Brachial Artery Distensibility, BMI, BP, lipids, CRP, and APN will be measured in the ongoing Princeton Landmark Study (N=2000). A cohort sample (n=450) will also undergo brachial flow mediated dilatation, augmentation index and pulse wave velocity. Contrasts in laboratory & vascular measures will be made among normals, obese and obese-insulin-resistant subjects. Well-established and newer non-invasive methods of vascular function testing will be compared. Relevance: Showing that metabolic abnormalities related to overweight lead to blood vessel dysfunction in children will help doctors identify high-risk children for early treatment to prevent future heart attack and stroke.