Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet in Diastolic Heart Failure

NCT00939640 | Completed Results

• 1 other identifier: HUM00025253
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure with preserved systolic function (HF-PSF, or 'diastolic heart failure') accounts for half of hospitalizations for heart failure in patients over the age of 65. Most HF-PSF patients have systemic hypertension (HTN), and characteristic HTN-induced cardiovascular changes contribute to HF-PSF. However, it is unclear why most patients with HTN never develop HF-PSF or which specific aspects of HTN predispose to HF-PSF. In the Dahl S rat, the primary animal model of HF-PSF, high dietary sodium intake suppresses the systemic renin-angiotensin-aldosterone system, but upregulates renal and cardiac renin-angiotensin-aldosterone system by inducing oxidative stress. In humans, the magnitude of blood pressure response to sodium ingestion and depletion can categorize subjects as "salt-resistant" and "salt-sensitive." Human salt sensitivity is associated with structural and loading conditions that increase the risk for HF-PSF, including HTN, ventricular hypertrophy and diastolic dysfunction, arterial stiffening, and increased plasma volume. High dietary sodium intake induces oxidative stress in salt-sensitive humans. In humans with HTN and normal ventricular systolic function that do not have heart failure, increased oxidative stress predicts impaired exercise capacity, ventricular hypertrophy, diastolic dysfunction, arterial stiffening, and vascular endothelial dysfunction. The investigators have proposed that "salt sensitivity" and the accompanying oxidative stress on the typical high-sodium Western diet may contribute to the initiation and progression of HF-PSF. In patients with HF-PSF, the investigators will relate dietary changes to biochemical and cardiovascular functional measures. The investigators will study subjects on ad-lib diet and and following three weeks of rigorous dietary modification with the Dietary Approaches to Stop Hypertension (DASH)/sodium-restricted diet (SRD). This diet is richer in natural antioxidants and lower in sodium than the usual American diet. The DASH/SRD is recommended to lower blood pressure in patients with HTN, and is particularly effective in elderly, obese, and salt-sensitive hypertensives. Dietary sodium restriction is recommended for all HF patients including those with HF-PSF. The investigators hypothesize that the DASH/SRD will have favorable effects on oxidative stress, ventricular and vascular function, and blood pressure control in patients with hypertensive HF-PSF.

Conditions

Diastolic Heart Failure; Hypertensive Heart Disease

Keywords

Diet; Sodium; Hypertension; Potassium; Antioxidants; congestive heart failure; Heart failure with normal ejection fraction; Heart failure with preserved systolic function

Outcome Measures

Primary Outcomes (1)

• Brachial Artery Flow-mediated Dilation (FMD)

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Secondary Outcomes (7)

• Mean 24-hour Systolic Blood Pressure

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

• Diurnal Variation in Ambulatory Blood Pressure

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

• Aortic Augmentation Index

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

• Carotid-femoral Pulse Wave Velocity

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

• Ventricular Diastolic Function

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Other Outcomes (2)

• EndoPAT Arterial Endothelial Function

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

• Estimated Glomerular Filtration Rate, Serum Potassium, Serum Calcium-phosphorus Product

  Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Study Arms (1)

Dietary intervention

EXPERIMENTAL

Diet patterned after the intervention in the DASH-Sodium trial (Sacks FM et al. New Engl J Med 2001;344(1):3-10). The diet includes higher quantities of fresh fruits and vegetables, whole grain products, and low-fat dairy products than the standard American diet. The target sodium content is 50 mmol per 2100 kcal, and the caloric content is intended to maintain body weight. The diet is designed, prepared, and packaged by research dietitians and all food and beverages are provided for study participants.

Behavioral: DASH/sodium-restricted diet (SRD)

Interventions

DASH/sodium-restricted diet (SRD) BEHAVIORAL

Baseline diet will be assessed via Block Food Frequency Questionnaire, and 24-hour urinary sodium, potassium, and 8-isoprostanes will be measured. Subjects will then be assigned to 21 days of the DASH/SRD, with all food and beverages provided. Adherence will be assessed through a three-day food diary at the midpoint of the intervention, and at the end of the study urinary sodium, potassium, and 8-isoprostanes will again be measured.

Also known as: DASH diet, sodium-restricted diet, low sodium diet, DASH-sodium

Dietary intervention

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Satisfy European Society of Cardiology guidelines for the diagnosis of HF-PSF (Paulus WJ et al. Eur. Heart J. 2007;28:2539-2550).
• Framingham criteria for heart failure satisfied
• left ventricular ejection fraction ≥ 50% (contrast ventriculography, echocardiography, nuclear scintigraphy)
• Diastolic dysfunction on previous echocardiogram/catheterization or evidence of abnormal neurohormonal activation (B-type natriuretic peptide (BNP) ≥ 100 pg/ml) with supporting evidence (atrial fibrillation, left atrial enlargement, left ventricular hypertrophy)
• History of systemic hypertension
• Willing to adhere to provided diet

You may not qualify if:

• New York Heart Association Class IV heart failure symptoms
• Hospitalization for decompensated heart failure within past one month
• Uncontrolled hypertension (seated systolic blood pressure ≥ 180 or diastolic blood pressure ≥ 110) at rest, on current antihypertensive regimen
• Changes in medical regimen for heart disease or hypertension within past 1 month, including diuretic dose adjustment
• Primary exercise limitation due to severe pulmonary disease
• Poor echocardiographic windows
• Worse than moderate mitral or aortic stenosis or insufficiency.
• Serum potassium level \> 5.0 mmol/L at baseline or prior history of serum potassium level \> 6.0
• Serum calcium/phosphorus product \> 50 at baseline
• Severe renal insufficiency (current estimated glomerular filtration rate \< 30 ml/min)
• Severe anemia (hemoglobin \< 9 g/dL)
• Uncontrolled diabetes mellitus (hemoglobin A1c \> 9%)
• Non-hypertensive cause of HF-PSF, e.g. amyloidosis, sarcoidosis, constrictive pericardial syndromes
• Myocardial infarction or unstable angina, including new or worsening anginal syndrome, within the past three months
• Uncontrolled arrhythmia (including non rate-controlled atrial fibrillation)

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (11)

• Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256.

  PMID: 16855265 BACKGROUND

• Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003 Jan 8;289(2):194-202. doi: 10.1001/jama.289.2.194.

  PMID: 12517230 BACKGROUND

• Klotz S, Hay I, Zhang G, Maurer M, Wang J, Burkhoff D. Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction. Hypertension. 2006 May;47(5):901-11. doi: 10.1161/01.HYP.0000215579.81408.8e. Epub 2006 Apr 3.

  PMID: 16585423 BACKGROUND

• Laffer CL, Bolterman RJ, Romero JC, Elijovich F. Effect of salt on isoprostanes in salt-sensitive essential hypertension. Hypertension. 2006 Mar;47(3):434-40. doi: 10.1161/01.HYP.0000202480.06735.82. Epub 2006 Jan 23.

  PMID: 16432053 BACKGROUND

• Dekleva M, Celic V, Kostic N, Pencic B, Ivanovic AM, Caparevic Z. Left ventricular diastolic dysfunction is related to oxidative stress and exercise capacity in hypertensive patients with preserved systolic function. Cardiology. 2007;108(1):62-70. doi: 10.1159/000095883. Epub 2006 Sep 25.

  PMID: 17003543 BACKGROUND

• Yugar-Toledo JC, Bonalume Tacito LH, Ferreira-Melo SE, Sousa W, Consolin-Colombo F, Irigoyen MC, Franchini K, Coelho OR, Moreno H Jr. Low-renin (volume dependent) mild-hypertensive patients have impaired flow-mediated and glyceryl-trinitrate stimulated vascular reactivity. Circ J. 2005 Nov;69(11):1380-5. doi: 10.1253/circj.69.1380.

  PMID: 16247215 BACKGROUND

• Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM200101043440101.

  PMID: 11136953 BACKGROUND

• Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct;28(20):2539-50. doi: 10.1093/eurheartj/ehm037. Epub 2007 Apr 11.

  PMID: 17428822 BACKGROUND

• Hummel SL, Seymour EM, Brook RD, Sheth SS, Ghosh E, Zhu S, Weder AB, Kovacs SJ, Kolias TJ. Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction. Circ Heart Fail. 2013 Nov;6(6):1165-71. doi: 10.1161/CIRCHEARTFAILURE.113.000481. Epub 2013 Aug 28.

  PMID: 23985432 RESULT

• Hummel SL, Seymour EM, Brook RD, Kolias TJ, Sheth SS, Rosenblum HR, Wells JM, Weder AB. Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction. Hypertension. 2012 Nov;60(5):1200-6. doi: 10.1161/HYPERTENSIONAHA.112.202705. Epub 2012 Oct 1.

  PMID: 23033371 RESULT

• Mathew AV, Seymour EM, Byun J, Pennathur S, Hummel SL. Altered Metabolic Profile With Sodium-Restricted Dietary Approaches to Stop Hypertension Diet in Hypertensive Heart Failure With Preserved Ejection Fraction. J Card Fail. 2015 Dec;21(12):963-7. doi: 10.1016/j.cardfail.2015.10.003. Epub 2015 Oct 20.

  PMID: 26497755 RESULT

Related Links

• Hypertension publication from this study

MeSH Terms

Conditions

Heart Failure, Diastolic; Hypertension; Heart Failure

Interventions

Dietary Approaches To Stop Hypertension; Diet, Sodium-Restricted

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: Dr. Scott Hummel
• Organization: University of Michigan

scothumm@med.umich.edu

734-998-7991

Study Officials

• Scott L Hummel, MD MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: July 15, 2009
• Study Start: July 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: October 15, 2019
• Results First Posted: October 22, 2018

Record last verified: 2019-10

Locations

US (1)