Heart failure with preserved ejection fraction (HFpEF) constitutes half of heart failure in the elderly, but has no evidence-based therapy due to incomplete understanding of pathophysiology. Over 80% of HFpEF patients have hypertension, but the specific aspects that contribute to HFpEF are undefined. In 'salt-sensitive'animal models, high dietary sodium intake induces oxidative stress and inflammation in the heart, kidneys, and vasculature that cause HFpEF. In humans, the predictors of salt-sensitive hypertension match HFpEF demographics. Moreover, high sodium intake in salt-sensitive persons increases systemic oxidative stress and worsens vascular abnormalities associated with HFpEF. Current guidelines recommend dietary sodium restriction in heart failure and hypertension, but no prior studies have reported on the physiological effects of dietary modification in hypertensive HFpEF. We propose that salt-sensitive hypertension and the typical American diet are important driving factors for the initiation and progression of hypertensive HFpEF. We hypothesize that dietary patterns recommended for hypertension will 1) improve cardiovascular physiology, and 2) decrease systemic and cellular oxidative stress and inflammation in patients with hypertensive HFpEF. We will test these hypotheses by providing three weeks of the sodium-restricted Dietary Approaches to Stop Hypertension (DASH) diet to 25 patients with hypertensive HFpEF. We will report diet-induced changes in blood pressure and in vascular and ventricular function using standard and novel non-invasive measures. We will correlate these findings with oxidative stress and inflammatory marker production in the systemic circulation, venous endothelial cells, and peripheral blood mononuclear cells. In an eight-week extension, we will facilitate DASH diet compliance and determine if adherence leads to sustained physiological improvement. The candidate for this mentored Patient-Oriented Career Development Award aims to complement his previous training with additional expertise in noninvasive physiological measurement, bionutritional knowledge and dietary assessment, and interventional clinical research design. In order to facilitate future collaboration with laboratory-based colleagues, in concert with the proposed study the candidate will also pursue didactic and experiential basic science training related to his research aims. The University of Michigan has committed abundant resources to support this proposal including the use of a metabolic kitchen, sample processing laboratory, and biorepository in addition to nursing, bionutrition, and laboratory staff in the NIH CTSA-funded Michigan Clinical Research Unit. The proposal is supported by a multidisciplinary mentorship group comprised of authorities in salt-sensitive hypertension, cardiovascular physiology, vascular and immune cell biology, bionutrition, and clinical trial design. The proposed studies should provide novel information about the importance of dietary factors in hypertensive HFpEF, and could eventually lead to new strategies for the treatment and prevention of this major public health threat.

Public Health Relevance

Over six million Americans have heart failure, and in the elderly over half of heart failure occurs with preserved ejection fraction (HFpEF). No evidence-based treatments currently exist for HFpEF due to incomplete understanding of its pathophysiology. The overarching goal of this proposal is to explore dietary mechanisms for the initiation and progression of HFpEF.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Scott, Jane
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
Hummel, Scott L; Herald, John; Alpert, Craig et al. (2016) Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction. J Geriatr Cardiol 13:450-7
Goonewardena, Sascha N; Stein, Adam B; Tsuchida, Ryan E et al. (2016) Monocyte Subsets and Inflammatory Cytokines in Acute Decompensated Heart Failure. J Card Fail 22:358-65
Baker, Harolyn; Oliver-McNeil, Sandra; Deng, Lili et al. (2015) Regional Hospital Collaboration and Outcomes in Medicare Heart Failure Patients: See You in 7. JACC Heart Fail 3:765-73
Wessler, Jeffrey D; Maurer, Mathew S; Hummel, Scott L (2015) Evaluating the safety and efficacy of sodium-restricted/Dietary Approaches to Stop Hypertension diet after acute decompensated heart failure hospitalization: design and rationale for the Geriatric OUt of hospital Randomized MEal Trial in Heart Failure (GO Am Heart J 169:342-348.e4
Adejumo, Oluwayemisi L; Koelling, Todd M; Hummel, Scott L (2015) Nutritional Risk Index predicts mortality in hospitalized advanced heart failure patients. J Heart Lung Transplant 34:1385-9
Mathew, Anna V; Seymour, E Mitchell; Byun, Jaeman et al. (2015) Altered Metabolic Profile With Sodium-Restricted Dietary Approaches to Stop Hypertension Diet in Hypertensive Heart Failure With Preserved Ejection Fraction. J Card Fail 21:963-7
Hummel, Scott L; Katrapati, Prashanth; Gillespie, Brenda W et al. (2014) Impact of prior admissions on 30-day readmissions in medicare heart failure inpatients. Mayo Clin Proc 89:623-30
Konerman, Matthew C; Hummel, Scott L (2014) Sodium restriction in heart failure: benefit or harm? Curr Treat Options Cardiovasc Med 16:286
Wessler, Jeffrey D; Hummel, Scott L; Maurer, Mathew S (2014) Dietary interventions for heart failure in older adults: re-emergence of the hedonic shift. Prog Cardiovasc Dis 57:160-7
Senni, Michele; Paulus, Walter J; Gavazzi, Antonello et al. (2014) New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J 35:2797-815

Showing the most recent 10 out of 16 publications