Dr. Longenecker, who trained in Internal Medicine (IM) at the Johns Hopkins Hospital (1990-1993), served as Associate Program Director for the IM Residency Program at Abington Memorial Hospital (1993-1996). He is seeking this MCSDA to study the epidemiology of atherosclerotic cardiovascular disease (ASCVD) in dialysis patients, complete a Ph.D. in Epidemiology and transition to an independent career in clinical research. Over the past year, he completed a Master of Public Health degree at Hopkins and joined the Welch Center for Prevention, Epidemiology and Clinical Research, one of the premiere sites for mentored clinical research in the country. Under the mentorship of Drs. Michael Klag and Josef Coresh, he received the NIDDK Renal Disease Epidemiology Training Grant, joined the CHOICE study (Choices for Healthy Outcomes in Caring for ESRD, an AHCPR-funded PORT), was appointed as a Clinical and Research Fellow in the Division of General Internal Medicine, co-authored a published paper with Dr. Klag, developed the proposed research plan, and finished writing a book on acid-base disorders to be published next year by Williams and Wilkins. Lipoprotein(a) [Lp(a)], homocysteine (tHcy) and ASCVD are markedly elevated in dialysis patients. However, there is insufficient evidence to establish Lp(a) and tHcy as independent risk factors for the increased incidence of ASCVD in this population. As an ancillary study of CHOICE, Dr. Longenecker plans to conduct a prospective study in 875 incident dialysis patients to investigate serum Lp(a) levels, Lp(a) isoforms and tHcy levels as risk factors for ASCVD. Dr. Longenecker has designed and initiated the ASCVD outcome data collection and validation procedures for the study. He will review the hospitalization records for ASCVD outcomes in the entire cohort. Lp(a) levels, Lp(a) isoforms and tHcy levels will be determined for each participant and will be analyzed as risk factors for ASCVD outcomes. Multivariate analyses will control for confounding by age, race, smoking, history of ASCVD, diabetes, hypertension, alcohol, body mass index, cholesterol, high and low density lipoproteins, triglycerides, and dialysis dose. The study will have sufficient power for a race- stratified analysis of interaction. Dr. Longenecker will later complete a meta-analysis of either Lp(a)- or tHcy-lowering therapies. Based on this quantitative review of the literature, he will conduct a clinical trial to test the efficacy of a promising Lp(a)- or tHcy-lowering therapy in dialysis patients. The combination of observational and experimental research in the supportive context of the Welch Center, CHOICE, and the Department of Epidemiology will give Dr. Longenecker the experience and tools he needs to develop into an Independent clinical scientist.
