The applicant, Dr. Sarah de Ferranti, is a pediatric cardiologist and Instructor in Pediatrics at Harvard University. Her long term goal is to become an independent clinician researcher in the assessment of vascular dysfunction and reduction of cardiovascular risk in children. Dr. de Ferranti has a longstanding interest in prevention;the pediatric obesity epidemic has focused her attention on adolescents with cardiovascular risk factors typical of the adult metabolic syndrome. Children with cardiovascular risk factors are likely to have cardiovascular and metabolic disease as adults. The proposed career development plan is necessarily multi-disciplinary, incorporating aspects of inflammatory physiology, nutritional lifestyle modification, and the conduct of an interventional clinical trial. Importantly, she will become proficient in vascular functional testing as a way of assessing pre-clinical atherosclerosis, allowing her to combine two areas of expertise rarely seen together, pediatric preventive cardiology and non-invasive vascular testing. Under the mentorship of Dr. David Ludwig, a pediatric endocrinologist experienced in obesity and nutrition, and Dr. Jane Newburger, a pediatric cardiologist with expertise in preventive cardiology and research, the applicant will investigate the effect of two nutritional strategies on cardiovascular risk factors. Using a feeding study design, the applicant will test the hypothesis that dietary strategy, independent of weight loss, affects cardiovascular risk factors. The protocol randomly assigns 46 overweight adolescents age 12-19 years with cardiovascular risk factors typical of the metabolic syndrome to receive either a low-fat diet or a low-glycemic load diet designed to induce a 5% weight loss over a period of 8 weeks. The primary outcome will be changes from baseline in insulin sensitivity as measured with an intravenous glucose tolerance test;other outcomes will include inflammation, coagulopathy, dyslipidemia, blood pressure, central obesity and body composition by DEXA. A secondary hypothesis to be tested is that vascular function measured by brachial artery reactivity and peripheral arterial tonometry will improve with weight loss, with larger changes from baseline in the low glycemic load group than the low fat diet. To our knowledge, this would be the first well- controlled feeding study to be conducted in overweight adolescents. The high prevalence of pediatric obesity in the United States makes greater understanding of the pediatric cardiovascular consequences essential.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (F1))
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Scott, Jane
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Children's Hospital Boston
United States
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Levenson, A E; Milliren, C E; Biddinger, S B et al. (2017) Calorically restricted diets decrease PCSK9 in overweight adolescents. Nutr Metab Cardiovasc Dis 27:342-349
Martinez, Enid E; Forbes, Peter W; O'Brien, Sharon E et al. (2016) Census tract based income level and lipid levels in urban pediatric primary care: a retrospective study. BMC Pediatr 16:86
de Ferranti, Sarah D; Milliren, Carly E; Denhoff, Erica Rose et al. (2015) Providing food to treat adolescents at risk for cardiovascular disease. Obesity (Silver Spring) 23:2109-17
de Ferranti, Sarah D; Milliren, Carly E; Denhoff, Erica R et al. (2014) Using high-dose omega-3 fatty acid supplements to lower triglyceride levels in 10- to 19-year-olds. Clin Pediatr (Phila) 53:428-38
Zachariah, Justin P; de Ferranti, Sarah D (2013) NHLBI integrated pediatric guidelines: battle for a future free of cardiovascular disease. Future Cardiol 9:13-22
de Ferranti, Sarah D; Gillman, Matthew W (2012) Hypertension in children and adolescents: more questions than answers. Arch Pediatr Adolesc Med 166:872-4
de Ferranti, Sarah D; Crean, Sheila; Cotter, Jill et al. (2011) Hypertriglyceridemia in a pediatric referral practice: experience with 300 patients. Clin Pediatr (Phila) 50:297-307
Gooding, Holly C; de Ferranti, Sarah D (2010) Cardiovascular risk assessment and cholesterol management in adolescents: getting to the heart of the matter. Curr Opin Pediatr 22:398-404
de Ferranti, Sarah D (2010) Recovery from metabolic syndrome is both possible and beneficial. Clin Chem 56:1053-5
Selamet Tierney, Elif Seda; Newburger, Jane W; Gauvreau, Kimberlee et al. (2009) Endothelial pulse amplitude testing: feasibility and reproducibility in adolescents. J Pediatr 154:901-5

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