Obesity is a critical public health issue, and is responsible for a growing prevalence of diverse comorbidities that reduce quality of life and increase mortality risk. Obesity is an important risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). Upregulation of the renin-angiotensin- aldosterone system, heightened sympathetic nervous system activity, vascular stiffness, and release of inflammatory cytokines contribute to the increased risk of CKD and CVD in obese patients. Accordingly, obesity is highly associated with the development of hypertension. As adiposity increases, patients are prone to glomerular hyperfiltration, amplified renal sodium reabsorption, extracellular volume overload, and impaired natriuresis. Thus, patients with excess adipose tissue are often more physiologically complex than lean hypertensive patients, and are at greater risk for many adverse outcomes related to hypertension. Nonetheless, little is known about appropriate blood pressure goals or the effects of specific antihypertensive agents on degree of blood pressure control in obese patients. The objective of the proposed studies is to better understand 1) if adiposity influences the effect of antihypertensive class on degree of BP control, and 2) the effect that degree of BP control has on the development and progression of CKD and CVD in obese, hypertensive patients. We will use prospective 24- hour ambulatory blood pressure monitoring in addition to longitudinal analyses of retrospective electronic health record data from two extremely largescale health systems, taking into account time-updated exposures and confounders. We will also use the electronic health record data to assess if there is a difference in initial antihypertensive class selection or BP threshold for initiation of antihypertensive treatment in obese versus non-obese patients. Using a multidisciplinary approach, we anticipate that this design will facilitate future optimization of medical management of patients with obesity and hypertension. I am currently funded by an NIH F32 grant, with board certification in Internal Medicine and Nephrology, and a Masters of Science in Clinical Epidemiology from the University of Pennsylvania. The K23 Career Development Award will enable me to develop research aimed at optimizing the pharmacologic management of the millions of obese, hypertensive patients living in the United States. My previous experience and training in longitudinal analyses have prepared me to engage in the work proposed in the studies, and will compliment my proposed intensive education in patient-oriented hypertension research, advanced longitudinal analytic techniques, pharmacoepidemiologic methods, and cardiovascular epidemiologic outcomes research. With the support of my highly experienced mentorship team and the ample resources available at the University of Pennsylvania?s Center for Clinical Epidemiology and Biostatistics, my goal is to foster a career of enduring research as an independent physician scientist, and to become a leader in the field of renal hypertension.

Public Health Relevance

Obesity is an important public health issue, and is a major risk factor for the development of kidney disease and heart disease. A number of complex factors contribute to the development of high blood pressure in these patients, however very little is known about the effects of different blood pressure medications or the appropriate blood pressure goals in obese people. The purpose of the proposed studies is to better understand the impact of different blood pressure medications on blood pressure control in obese individuals, and to assess for the effect of blood pressure control on the risk of developing kidney disease or heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HL133843-01
Application #
9163194
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Huang, Li-Shin
Project Start
2016-09-01
Project End
2021-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Cohen, Jordana B; Locke, Jayme E; Shelton, Brittany et al. (2018) Disparity in Access to Kidney Allograft Offers Among Transplant Candidates with Human Immunodeficiency Virus. Clin Transplant :e13466
Cohen, Jordana B; Padwal, Raj S; Gutkin, Michael et al. (2018) History and Justification of a National Blood Pressure Measurement Validated Device Listing. Hypertension :HYPERTENSIONAHA11811990
Suarez, Jonathan; Cohen, Jordana B; Potluri, Vishnu et al. (2018) Racial Disparities in Nephrology Consultation and Disease Progression among Veterans with CKD: An Observational Cohort Study. J Am Soc Nephrol 29:2563-2573
Cohen, J B; Owei, L; Sawinski, D L et al. (2018) Inferior long-term allograft and patient outcomes among recipients of offspring living donor kidneys. Am J Transplant 18:1699-1709
Cohen, J B; Shults, J; Goldberg, D S et al. (2018) Kidney allograft offers: Predictors of turndown and the impact of late organ acceptance on allograft survival. Am J Transplant 18:391-401
Cohen, Jordana B; Perlis, Michael L; Townsend, Raymond R (2018) Systolic blood pressure as a potential target of sigma-1 receptor agonist therapy. J Clin Hypertens (Greenwich) 20:416-417
Cohen, Jordana B; Tewksbury, Colleen M; Torres Landa, Samuel et al. (2018) National Postoperative Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease and End-Stage Kidney Disease. Obes Surg :
Shulman, Rachel; Cohen, Debbie L; Grandner, Michael A et al. (2018) Sleep duration and 24-hour ambulatory blood pressure in adults not on antihypertensive medications. J Clin Hypertens (Greenwich) 20:1712-1720
Cohen, Jordana B; Eddinger, Kevin C; Locke, Jayme E et al. (2017) Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist. Clin J Am Soc Nephrol 12:974-982
Cohen, Jordana B (2017) Hypertension in Obesity and the Impact of Weight Loss. Curr Cardiol Rep 19:98

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