Diet and pathophysiology of heart failure with preserved ejection fraction

Summary

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

Top Publications

  1. pmc Prevalence of cognitive impairment in older adults with heart failure
    Tanya 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
  2. pmc Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction
    Scott 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
  3. pmc Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction
    Scott L Hummel
    Department of Internal Medicine
    Circ Heart Fail 6:1165-71. 2013
  4. pmc Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients
    Scott 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
  5. pmc Impact of prior admissions on 30-day readmissions in medicare heart failure inpatients
    Scott 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

Research Grants

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
  2. PPG - Mechanisms of Cardiovascular Protection and Disease
    Donald D Heistad; Fiscal Year: 2013
  3. Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
    Kathy K Griendling; Fiscal Year: 2013
  4. Discovery and Development of Therapeutic Genes for CHF
    H Kirk Hammond; Fiscal Year: 2013
  5. BIOLOGY OF NEUROENDOCRINE PEPTIDES
    Marc R Montminy; Fiscal Year: 2013
  6. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
  7. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
  8. Immune-Based Interventions Against Infectious Diseases
    Alan L Rothman; Fiscal Year: 2013
  9. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
  10. Blood Pressure Regulation: Novel Roles for the Kidney
    Pablo A Ortiz; Fiscal Year: 2013

Detail Information

Publications7

  1. pmc Prevalence of cognitive impairment in older adults with heart failure
    Tanya 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)...
  2. pmc Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction
    Scott 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...
  3. pmc Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction
    Scott 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...
  4. pmc Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients
    Scott 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...
  5. pmc Impact of prior admissions on 30-day readmissions in medicare heart failure inpatients
    Scott 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...

Research Grants30

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  2. PPG - Mechanisms of Cardiovascular Protection and Disease
    Donald D Heistad; Fiscal Year: 2013
    ..abstract_text> ..
  3. Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
    Kathy K Griendling; Fiscal Year: 2013
    ..Ultimately, this research may establish new unifying concepts linking conditions that alter vascular oxidant stress and inflammation to the molecular processes underlying vasculopathies. (End of Abstract) ..
  4. Discovery and Development of Therapeutic Genes for CHF
    H Kirk Hammond; Fiscal Year: 2013
    ..Four Cores will support the Program: Digital Imaging (Dr. Farquhar);Vector Production (Dr. Miyanohara);Translational Systems (Dr. Hammond) and Clinical &Administrative (Dr. Hammond). ..
  5. BIOLOGY OF NEUROENDOCRINE PEPTIDES
    Marc R Montminy; Fiscal Year: 2013
    ..Specifying the contributions of the CRF family of ligands and receptors to the maintenance of homeostasis and to stress-linked allostasis may improve our ability to manage diseases, including mood and metabolic disorders ..
  6. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
    ..These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract) ..
  7. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
    ..By using multidisciplinary approaches, we will determine the structural identity of lipid mediators, the molecular mechanisms involved in their production and how they function to regulate lung responses. ..
  8. Immune-Based Interventions Against Infectious Diseases
    Alan L Rothman; Fiscal Year: 2013
    ..3. Recruit promising junior investigators and provide mentoring by established NIH-funded researchers. 4. Support a multidisciplinary research program led by junior investigators in translational infectious diseases immunology. ..
  9. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
    ..ular tone, in the pathophysiology of hypertension and cardiovascular disease. ..
  10. Blood Pressure Regulation: Novel Roles for the Kidney
    Pablo A Ortiz; Fiscal Year: 2013
    ..Thus it will accelerate acquisition of knowledge of the novel mechanisms by which the kidney regulates blood pressure, and may provide new targets for anti-hypertensive drugs. ..
  11. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
    ..A major objective of this Program Project is to inform decisions of the IPF Clinical Network by providing information that can be translated into novel therapeutic strategies for IPF. ..
  12. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  13. Mechanisms of Microvascular Control and Coordination in Health and Disease
    Gerald A Meininger; Fiscal Year: 2013
    ..End of Abstract) ..
  14. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  15. Interactive Signaling Modules in Vascular Inflammation
    Linda H Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
  16. Novel Mechanisms and Therapies in Heart Failure
    Howard A Rockman; Fiscal Year: 2013
    ..The results will be used to define novel strategies for manipulation of these recently discovered mechanisms for the therapy of patients with heart failure. ..