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

Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet on Ventriculovascular Function in Heart Failure With Preserved Systolic Function

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00939640

Acronym

DASH-DHF

Enrollment

Registered

2009-07-15

Start date

2009-07-31

Completion date

2011-05-31

Last updated

2019-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

BEHAVIORALDASH/sodium-restricted diet (SRD)

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
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

Measure	Time frame	Description
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
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	—
Six Minute Walk Test Distance	Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation	—
Urinary 8-isoprostanes	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

Other

Measure	Time frame	Description
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	Safety measures to determine adverse effects of the provided DASH diet home-delivered meals

Countries

United States

Participant flow

Recruitment details

22 patients screened, 14 enrolled

Participants by arm

Arm	Count
Dietary Intervention 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. DASH/sodium-restricted diet (SRD) : 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.	14
Total	14

Arm

Count

Dietary Intervention

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. DASH/sodium-restricted diet (SRD) : 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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Physician Decision	1

Baseline characteristics

Characteristic	Dietary Intervention
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	14 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Age, Continuous	72 years STANDARD_DEVIATION 10
Body mass index	35.5 kg/m^2 STANDARD_DEVIATION 7.9
Coronary Artery Disease	5 Participants
Hypertension	14 Participants
New York Heart Assocation Classification NYHA Class II	2 Participants
New York Heart Assocation Classification NYHA Class III	12 Participants
Participants on 3 or more antihypertensive medications	10 Participants
Participants on chronic loop diuretics	11 Participants
Participants with Chronic Kidney Disease	14 Participants
Participants with prior hospitalization due to heart failure	10 Participants
Participants wtih Anemia	6 Participants
Participants wtih Diabetes Mellitus	6 Participants
Region of Enrollment United States	14 participants
Sex: Female, Male Female	13 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	1 / 14
serious Total, serious adverse events	0 / 14