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

Not Applicable

Completed

Conditions: Diastolic Heart Failure
Hypertensive Heart Disease

Interventions: Behavioral: DASH/sodium-restricted diet (SRD)

Registration Number: NCT00939640

Lead Sponsor: University of Michigan

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

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

Exclusion Criteria

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)
Terminal illness expected to result in death within six months or active solid-organ cancer
Psychiatric disorder or dementia with potential to compromise dietary adherence

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dietary intervention	DASH/sodium-restricted diet (SRD)	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Mean 24-hour Systolic Blood Pressure	Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation	Change in 24-hour systolic blood pressure
Diurnal Variation in Ambulatory Blood Pressure	Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation	Number of participants with non-dipping of nocturnal blood pressure - nighttime-to-daytime systolic BP ratio of \>= 0.9
Six Minute Walk Test Distance	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	Aortic augmentation index is the ratio of the augmentation pressure to the central pulse pressure, expressed as a percentage. Both parameters are obtained via mathematical transformation of the radial pulse wave. The augmentation pressure represents the contribution of reflected waves to the pulse pressure. The central pulse pressure is the ratio between maximum aortic systolic pressure and minimum aortic diastolic pressure. A higher aortic augmentation index and central pulse pressure reflect increased arterial stiffness. Increased arterial stiffness is associated with an increased long-term risk of cardiovascular disease.
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	Lateral mitral annulus E/e' ratio
Urinary 8-isoprostanes	Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation