HTN: Sodium (2015)


Jablonski K, Fedorova O, Racine M, Geolfos C, Gates P, Chonchol M, Fleenor B, Ladatta E, Bagrov A, Seals D. Dietary sodium restricition and association with urniary marinobufagenin, blood pressure and aortic stiffness. Clin J Am Soc Nephol. 2013 Nov; 8(11): 1952-1959.

PubMed ID: 3817896
Study Design:
Randomized Crossover Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
  • To examine the effect of dietary sodium restriction on urinary marinobufagenin (MBG) excretion and aortic pulse-wave velocity and assess associations between urinary MBG excretion, blood pressure, aortic pulse-wave velocity and markers of oxidative stress over the duration of the study
  • To test the hypothesis that dietary sodium restriction in middle-aged or older adults with moderately elevated systolic blood pressure would reduce urinary marinobufagenin excretion as well as systolic blood pressure and aortic pulse-wave velocity .
Inclusion Criteria:
Patients from the parent study who:
  • Were non-smokers
  • Had a body mass index less than 40
  • Had a resting systolic blood pressure of 130mm Hg to 159mm Hg and diastolic blood pressure less than 99mm Hg
  • Free of cardiovascular disease, diabetes, kidney disease or other clinical disorders
  • Did not take supplements known to influence vascular function (antioxidants) or hormone replacement therapy (post-menopausal women)
  • Were either sedentary or recreationally active.
More detailed inclusion information may be available in the parent study.
Exclusion Criteria:
  • Taking antihypertensive medications
  • Numerous missing urine samples (one subject).
Description of Study Protocol:


Double-blind, placebo-controlled, randomized, crossover design.

Blinding Used

Placebo and intervention items were provided as a pill so subjects were blinded to variations in treatment. Researchers were blinded to treatment assignment. All subjects received same the education, instructions and analysis throughout the study period.


During a 10-week intervention, subjects had low-sodium intake (1,500mg per day) for five weeks and normal intake (3,600mg per day) for five weeks provided as pills of placebo or slow-release sodium chloride.

Statistical Analysis

  • Linear mixed effects model with covariance structure (Toeplitz)
  • Paired T-tests, ANOVA with post-hoc Bonferonni corrected comparisons
  • Pearson correlation, stepwise multiple linear regression
  • Significance with P<0.05.
Data Collection Summary:

Timing of Measurements

  • Baseline (two measurements of 24-hour urine and blood pressure) and weekly (10)
  • Aortic pulse-wave velocity and endothelial cell protein at end of each sodium treatment (Week Five and 10).

Dependent Variables

  • Systolic blood pressure (mm Hg)
  • MBG excretion (mmol per day)
  • Aortic pulse-wave velocity (percent).

Independent Variables

Dietary sodium restriction.

Control Variables

  • Age
  • Sex
  • BMI
  • A 24-hour urinary sodium excretion.
Description of Actual Data Sample:
  • Initial N: N=17 subjects in parent study
  • Attrition (final N): N=11 subjects appropriate for this subset study (eight male, three female)
  • Age: 60±2 years
  • Anthropometrics: Subjects served as own controls
  • Location: The University of Colorado Boulder Clinical and Translational Research Center, United States.


Summary of Results:

Key Findings

Changes in Clinical Characteristics
Variable Baseline Low Sodium Normal Sodium
Urine sodium (mmol per 24 hours) 159±13 77±9a 144±7
SBP (mm Hg) 139±2 127±3b 138±5
DBP (mm Hg) 83±2 77±2 81±2

a P<0.01 vs. baseline or normal sodium (P=0.002 vs. baseline and P=0.006 vs. normal sodium)
b P<0.001 vs. baseline or normal sodium.
  • Urinary marinobufagenin (MBG) excretion, systolic blood pressure and aortic pulse-wave velocity were lower during the low-sodium vs. normal-sodium condition (P<0.05)
  • Urinary MBG was reduced during the low-sodium phase only and was related to urinary sodium excretion (R=0.46, P<0.001)
  • Aortic pulse-wave velocity was reduced by 17% during the low-sodium condition.

Other Findings

All subjects reduced sodium excretion and systolic blood pressure.

Author Conclusion:
This study shows, for the first time in humans, that dietary sodium restriction reduces urinary marinobufagenin (MBG) excretion and that MBG excretion is positively associated with systolic blood pressure and aortic stiffness in middle-aged and older adults with moderately elevated systolic blood pressure..
Funding Source:
Government: National Institute on Aging, Natinal Institutes of Health
University/Hospital: University of Colorado Boulder
Reviewer Comments:
  • Subjects reduced sodium excretion and SBP similarly to the entire cohort
  • Authors note small study population size
  • Article includes multiple references to parent study
  • The study reviewed here is a subset of the parent study [Jablonski KL, Racine ML, Geolfos CJ, Gates PE, Chenchol M, McQueen MB, Seals DR. Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure. J Am Coll Cardiol. 2013; 61: 335-343 (PubMed: 23141486)]
  • Changes in clinical characteristics of participants in this study were similar to the entire cohort.
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? ???
  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? ???
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) Yes
  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")? Yes
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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  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? Yes
  5.5. In diagnostic study, were test results blinded to patient history and other test results? Yes
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? Yes
  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? Yes
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? Yes
  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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? N/A
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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes