The proposed Washington Area Comprehensive Sickle Cell Center includes Howard University, a historically-black teaching institution in the nation's capital, Children's National Medical Center, the premier provider of healthcare to children with sickle cell disease (SCD) in the area, and the Vascular Medicine Branch of NHLBI, an internationally recognized unit that leads in the investigation of the vascular complications of SCD. The proposed Center also includes collaboration with Ahmadu Bello University in Zaria, Nigeria, an institution that treats many SCD patients who have not yet been exposed to blood transfusions or hydroxyurea. The primary focus of the proposed center is to improve understanding, prevention and treatment of the vascular complications of SCD. The components of the project are: 1. An inter-Center Phase II Study of therapy with a nitric oxide-donating combination compared to an angiotensin converting enzyme inhibitor or placebo in preventing renal dysfunction, pulmonary hypertension, stroke and other complications in SCD patients with systemic systolic blood pressure of 120-139 mm Hg. 2. An intra-Center clinical study to determine the prevalence of pulmonary hypertension in Nigerian SCD patients using echocardiographic measurements of the tricuspid regurgitant jet velocity, the contribution of HIV/AIDS and malaria, and the role of genetic polymorphisms in candidate genes that regulate endothelial function and adhesion. 3. A patient services research project to identify the prevalence of developmental problems among infants and toddlers with SCD compared to age and demographically matched controls. 4. A translational research project that seeks to raise levels of HDL and therefore apoA-1 to improve endothelium-dependent vasorelaxation by administration of the NAD precursor, niacin. 5. An Administrative Core. 6. A Clinical Core that includes the adult and pediatric sickle cell clinics at Howard University, the pediatric sickle cell clinic at Children's National Medical Center, the adult sickle cell clinic at NHLBI, and their associated personnel. 7. A Patient Services Core focusing on education, community outreach, genetic counseling and diagnostic testing. 8. A Sickle Cell Scholar Component.
