EAL

HESI: Congestive Heart Failure Population (2014)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the effect of dietary sodium restriction on neurohumoral activation and renal dopaminergic system response in mild-to-moderate compensated heart failure (HF).

Inclusion Criteria:

Mild-to-moderate HF
Left ventricular ejection fraction lower than 40%
No exacerbations or therapeutic changes in the previous two months.

Exclusion Criteria:

Concomitant significant valve disease
Renal or hepatic failure
Diabetes mellitus
Pulmonary disease.

Description of Study Protocol:

Recruitment: Not described
Design: RCT
Blinding used: Not reported
Intervention: Low-sodium diet (2,300mg per day sodium) vs. usual-salt diet.

Statistical Analysis

Mann-Whitney U-test was used to evaluate differences in numerical variables between the two groups
Wilcoxon's signed-ranks test was used to test for differences between measurements performed at baseline and after the 15-day diet period
For comparisons of categorical variables, the likelihood ratio, Chi-square or Fisher's exact test were used when appropriate
Data are expressed as means ±SEM
P<0.05 is considered statistically significant
Statistical analysis was performed using the Statistical Package for Social Sciences software (SPSS).

Data Collection Summary:

Timing of Measurements
Baseline and after 15 days.

Dependent Variables

Urinary Sodium (UNa): 24-hour urine collection. The assay of sodium in urine was performed by indirect potentiometry, using the autoanalyzer Beckman Synchron CX3.
Fractional excretion of sodium: Calculated using the equation [UNa x PCr) / PNa x UCr] x 100, where UNa is urinary sodium, PNa is plasma sodium, UCr if urinary creatinine and PCr is plasma creatinine
Creatinine clearence: The assay of creatinine in urine and plasma samples was performed using the kinetic technique with Jaffe reaction, also using the satoanalyzer Beckman Synchron CX3 and creatinine clearance was calculated according to the formula [(UCr / PCr) x UVol] / 1,440, where UCr is urinary creatinine, PCR is plasma creatinine and UVol is urine volume
L-DOPA, dopamine, DOPAC, homovanillic acid, noradrenaline and creatinine urinary: 24-hour urine collections. Quantification of catecholamines and its metabolites in urine (L-DOPA, dopamine, DOPAC, homovanillic acid and noradrenaline) and plasma samples (L-DOPA, dopamine, DOPAC, homovanillic acid and noradrenaline) was performed by high-performance liquid chromatography with electrochemical detection.
B-type natriuretic peptide (BNP): Immunoradiometric assay.

Independent Variables

Low-sodium diet containing 2,300mg per day of sodium.

Description of Actual Data Sample:

Initial N: 24; (17 males, seven female)
Attrition (final N): Not reported
Age: 68.2±3.7 years in control and 71.5±2.7 years in low-sodium
Ethnicity: Not reported.

Other Relevant Demographics

Most of the subjects were on angiotensin-converting enzymen inhibitiors and the remainder on angiotensin II antagonists
None were on spironolactone, non-steroidal anti-inflammatory drugs or other drugs known to affect sodium handling or renal production of dopamine
Both groups were similar in usage of diuretics, beta-blockers and digoxin
There were no significant differences in ischemic etiology, atrial fibrillation, NYHA class, left ventricle ejection fraction or medications.

Anthropometrics
There were no significant differences in body surface area.

Location
Hospital S. Joao, Porto, Portugal.

Summary of Results:

Key Findings
Difference within groups (basal vs. after intervention)

Variables	Low-Sodium Diet			Normal Sodium Diet
Variables	Baseline	After	Statistical Significance of Group Difference (P-Value)	Baseline	After	Statistical Significance of Group Difference
Urine Volume (ml/day^-1)	2,046±231	1,640±223	<0.05	1,719±229	1,686±148	NS
Urine Creatinine (g/day^-1)	1.22±0.11	1.15±0.11	NS	1.3±0.09	1.3±0.08	NS
Urine Sodium (mEq/day^-1)	186.2±23.4	107.1±14.0	<0.05	152.3±20.0	159.5±18.2	NS
Creatinine Clearance (ml/minute^-1 1.73m^-2)	69.75±9.3	57.91±5.4	<0.05	81.45±8.9	69.84±6.9	NS
Fractional Excretion of Sodium	1.53±0.24%	1.00±0.18%	<0.05	1.05±0.18%	1.2±0.15%	NS

Differences in the Variation of Low Diet vs. Normal Diet

Variables	Low Sodium Diet	Normal Sodium Diet	Statistical Significance of Group Difference (P-Value_
Variation in Urinary Sodium (mEq/day^-1)	-79.2±18.2	7.25±13.6	0.001
Variation in Fractional Excretion of Sodium	-0.54±0.13%	0.16±0.14%	0.002
Variation in Plasma BNP (pg/ml^-1)	-86.0±38.6	-5.5±26.6	<0.02
Variation in Urinary Dopamine/L-DOPA (mcmol/day^-1)	3.16±1.45	-1.75±0.98	0.007
Variation in Plasma Aldosterone (pg/ml^-1)	80.2±57.2	11.3±16.9	0.16

Other Findings

NYHA functional class was not affected by sodium restriction
The renal delivery of L-DOPA and the urinary excretion of L-DOPA were significantly reduced by the low-sodium diet (P<0.05), while dopamine and its metabolites were not affected (NS)
Urinary dopamine-to-L-DOPA ratio (P<0.05) and urinary dopamine-to-renal delivery of L-DOPA ratio (P=0.03) were significantly increased by the low-sodium diet
Plasma L-DOPA decreased, while plasma dopamine increased on the low-sodium diet (both P<0.05)
Plasma aldosterone rose slightly (P=0.08) and BNP significantly decreased (P<0.05) on the low-sodium diet
None of these occurred in the controls.

Author Conclusion:

Salt restriction in patients with mild to moderate stable HF under diuretic therapy may induce volume depletion and neurohumoral activation. However, increases in the renal rate of L-DOPA utilization during sodium restriction may relate to activation of counter-regulatory mechanism.

Funding Source:

Other:

Not reported

Reviewer Comments:

The low-sodium diet described here may not be categorized as low in sodium because less than 2,300mg per day of sodium should be the maximum intake as recommended by 2010 Dietary Guidelines for Americans. Therefore, the impact of this "low-sodium" diet may jeopardize the results.
Small sample size increases risk for type 2 error.

What was the baseline nutrient status (i.e., sodium)? For example, the baseline sodium status can be used as an inclusion criterion for entry into study and recorded in the report of the trial.	Low-Sodium Group: 186.2±23.4mEq per day Control Sodium Group: 152.3±20mEq per day
What was the target of sodium intake in the intervention and comparison groups?	Low Sodium Diet: 2,300mg per day Usual Sodium Diet: Not reported
Was the difference in sodium status (i.e., change in urinary sodium excretion) measured between groups? If so, please specify.	Low-Sodium Group: Variation, -79.2.18.2mEq/day (from 186.2mEq to 107.1mEq/day) Control Group: Variation, 7.25±13.6mEq/day (from 152.3mEq to 159.5mEq/day) PS: Measurement of differences in the variations of sodium excretion between low and normal sodium diets.
Was the status of other nutrients (e.g., potassium and calcium) measured in order to ensure that the test nutrient (i.e., sodium) is the only nutrition-related, limiting factor in the response? If yes, please specify.	No.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???