Diet and pathophysiology of heart failure with preserved ejection fraction
Principal Investigator: Scott L Hummel
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2011-08-01 - 2016-06-30
more information: NIH RePORT
- Prevalence of cognitive impairment in older adults with heart failureTanya R Gure
Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
J Am Geriatr Soc 60:1724-9. 2012..To determine the prevalence of cognitive impairment in older adults with heart failure (HF)...
- Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fractionScott L Hummel
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 East Medical Center Dr, CVC Room 2383, SPC 5853, Ann Arbor, MI 48109, USA
Hypertension 60:1200-6. 2012..Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF...
- Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fractionScott L Hummel
Department of Internal Medicine
Circ Heart Fail 6:1165-71. 2013..We hypothesized that the sodium-restricted dietary approaches to stop hypertension diet (DASH/SRD) would improve left ventricular diastolic function, arterial elastance, and ventricular-arterial coupling in hypertensive HFPEF...
- Risk stratification for death and all-cause hospitalization in heart failure clinic outpatientsScott L Hummel
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI Electronic address
Am Heart J 166:895-903.e1. 2013..We hypothesized that routinely collected clinical data could predict the 6-month risk of death and all-cause medical hospitalization in HF clinic outpatients...
- Impact of prior admissions on 30-day readmissions in medicare heart failure inpatientsScott L Hummel
Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI Section of Cardiology, Ann Arbor Veteran s Affairs Medical Center, Ann Arbor, MI Electronic address
Mayo Clin Proc 89:623-30. 2014..To determine how all-cause hospitalizations within 12 months preceding an index heart failure (HF) hospitalization affect risk stratification for 30-day all-cause readmission...
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