The purpose of this K23 proposal is to provide Tara I. Chang, MD, MS with the protected time and resources to allow her to pursue the additional training needed to reach her long-term goal of becoming an independent patient-oriented investigator. Dr. Chang is a board-certified nephrologist and trained epidemiologist, and her research focuses on the intersection of cardiovascular disease and chronic kidney disease (CKD). Chronic kidney disease confers an increased risk for cardiovascular morbidity and mortality, and cardiovascular disease is the leading cause of death in CKD. Visit-to-visit blood pressure variability (BPV), defined as variation in blood pressure that occurs over days to months, is emerging as an important risk factor for death and cardiovascular events independent of mean or usual blood pressure in patients without CKD. Relatively little is known about visit-to-visit BPV in patients with CKD, a population at high risk for adverse clinical event. In addition, to date there is no uniform metric used to characterize visit-to-visit BPV. This projet proposes a series of analyses in patients with CKD, including end-stage renal disease (ESRD), to close some of the evidence gaps related to determinants and consequences of visit-to-visit BPV in this population.
The specific aims of this project are to define the best metrics of visit-t-visit BPV;better characterize traditional and patient-centered determinants of visit-to-visit BPV; compare the effectiveness of antihypertensive medications on clinical outcomes and evaluate whether differences are mediated by differences in visit-to-visit BPV;and evaluate the incremental prognostic value of visit-to-visit BPV as a novel risk marker beyond systolic, diastolic, or mean arterial blood pressure. The proposed work has high potential to make a significant clinical impact, as completion of the project aims will not only advance the current understanding of visit-to-visit BPV in CKD, but also provide preliminary data on putative risk factors to target in a future intervention trial aimed at lowering visit-to-visit BPV and improving clinical outcomes. Importantly, the proposed work is realistic and feasible within the award period, and will allow Dr. Chang to continue to build research skills, generate preliminary data, create additional collaborative networks, and compete for R01 funding. In summary, the K23 award will support the proposed training and career development activities to allow Dr. Chang to launch successfully into the next phase of her career as an independent clinical investigator.
Blood pressure can fluctuate a great deal from one day to the next (a phenomenon known as visit-to-visit blood pressure variability), and this variability may be a risk factor for heart disease, stroke, death, and other important clinical outcomes. Currently, not much is known about visit-to-visit blood pressure variability, particularly in persos with kidney disease, who are at very high risk of cardiovascular disease and other adverse outcomes. The current proposal aims to shed some light on this important topic by evaluating the determinants and consequences of visit-to-visit blood pressure variability in persons with kidney disease.