Disorders of Lipid Metabolism and Micronutrients

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

The researchers tested the hypothesis that sodium chloride and sodium bicarbonate have divergent effects on blood pressure.

Inclusion Criteria:

Included were normal subjects with a blood pressure of less than 140/90mm Hg who had never been told that they were hypertensive. Hypertensive subjects had mild hypertension and were treated with a single drug. Prior to entry in the study, the hypertensive subjects were instructed to stop taking this medication for two weeks and were to have a blood pressure of more than 140/90mm Hg. No female subjects were taking oral contraceptives.

Exclusion Criteria:

Not reported but assumed to be any subjects who did not meet the inclusion criteria.

Description of Study Protocol:

Recruitment

Volunteers were recruited from the Clinical Research Center.

Design

Randomized, placebo-controlled, crossover.

Blinding Used

Double blind.

Intervention  

  • Subjects were fed a basal diet of 80 grams of protein, 60mmol of sodium, 60mmol of chloride, 60mmol of potassium, and 600mg (14mmol) of calcium. Carbohydrate and fat contents were adjusted according to the subjects' size and desires.
  • During a separate phase, subjects consumed either three liters daily of a mineral water mix with 26.2mmol per liter of sodium, 0.71mmol per liter of potassium, 2.18mmol per liter of magnesium, 3.04mmol per liter of calcium, 4.23mmol per liter of chloride, and 33.03mmol per liter of bicarbonate. A control solution with equimolar amounts of cations as the chloride salt was administered for seven days. Both regimens increased total sodium to 138mmol per day.

Statistical Analysis

  • Two-way repeated measures analysis of variance was used to compare repeated variables and initial and final values in all subjects
  • Three-way analysis of variance was used to study the simultaneous effects of race, regimens and hypertension
  • Individual comparisons between regimens, diagnoses and race used Student's T-test when needed. They were applied when a positive interaction term was identified by analysis of variance.
  • Relationships between variables were assessed with Pearson correlation coefficients
  • Statistical analysis was performed on the square root of the value since plasma renin activity did not have normal distribution
  • 95% confidence intervals were significant
  • Data were expressed as means±SD.

 

Data Collection Summary:

Timing of Measurements 

  • There were two phases of 11 days each. Food and liquids were consumed at the Clinical Research Center, and subjects ingested only what was given to them by the dietary assistants. The same foods were served at every meal for every day of both phases of the study.
  • Subjects consumed a daily fixed basal diet of protein, sodium, chloride, potassium and calcium
  • On the fifth day, subjects were weighed in the morning before breakfast. On the basis of the authors' previous studies, a four-day period was allowed for subjects to achieve sodium balance. The subjects rested for 10 minutes, and blood pressure and heart rate were measured for at least 720 heart beats.
  • After balance was achieved, subjects were randomly assigned to three liters of mineral water mixture or three liters of control solution for seven days
  • On the eleventh day, subjects were given a lithium carbonate tablet. On the next morning, blood samples and blood pressure measurements were repeated with the addition of a lithium measurement in plasma and urine.
  • One month later, subjects followed the opposite regimen.

Dependent Variables

  • Blood pressure and heart rate (measured with automated Dinamap)
  • Plasma renin activity and plasma aldosterone (measured by radio-immunoassy)
  • Plasma sodium, chloride, plasma phosphate, urate, norepinephrine, epinephrine, dopamine (the latter three were measured using high performance liquid chromotography and electrochemical detection, by the method of Goldstein et al, listed in the reference section of this article)
  • Urinary excretion of sodium, potassium, calcium, chloride, phosphate, urate and creatinine (creatinine, urate, phosphate and electrolytes were measured with standard automated techniques).  

Independent Variables 

  • Basal diet
  • Mineral water mixture.

Control Variables

Control solution with equimolar amounts of cations as the chloride salt for seven days 138mol per day.

 

 

Description of Actual Data Sample:
  • Initial N: 20 (10 males, 10 females)
  • Attrition (final N): 20 (10 normotensive, 10 hypertensive)
  • Age: Mean age 36±9 years (range 20 to 56 years)
  • Ethnicity: Five normotensive whites, five hypertensive whites, five normotensive African-Americans, five hypertensive African-Americans
  • Anthropometrics: Baseline (pre-trial) subject characteristics not reported
  • Location: Indiana State University School of Medicine Clinical Research Center and two authors were from Wayne State University School of Medicine.
Summary of Results:

Sodium Chloride and Sodium Bicarbonate

  • Neither sodium chloride nor sodium bicarbonate had an effect on blood pressure in normotensive subject
  • Mildly hypertensive had no blood pressure increase from sodium chloride
  • Sodium bicarbonate administration caused a significant decrease in systolic blood pressure in hypertensives
  • Sodium chloride and sodium bicarbonate did not influence heart rate. Body weight and other plasma variables were not affected.
  • No effect of order on blood pressure was noted
  • No differences were noted in sodium excretion or calculated accumulation between regimens, between hypertensive and normotensive subjects, or between white and African-American subjects.

Urinary Excretion

  • Urinary chloride excretion increased only with sodium chloride but not with sodium bicarbonate
  • Potassium excretion was not influenced by regimen, diagnosis or race
  • Urinary calcium excretion was greater during the sodium chloride phase than with sodium bicarbonate (P<0.05). An effect of race and blood pressure was observed. On the last day, urinary calcium excretion was greater with sodium chloride than sodium bicarbonate (P<0.05), greater in hypertensives than normotensives (P<0.05) and greater in whites than in African-Americans (P<0.05).
  • Urate excretion did not differ between subjects with high blood pressure and normal blood pressure. However, African-Americans excreted less urate than whites on either regimen on all days tested (P<0.001), and their weights were comparable to whites. On the last day, African-Americans excreted significantly less urate with sodium chloride and sodium bicarbonate than whites (P<0.05).

Plasma Renin Activity

Plasma renin activity decreased significantly with both regimens in hypertensive subjects (P<0.05). No significance was observed in normal subjects or with catecholamine values.

 

Author Conclusion:

Sodium chloride increases calcium excretion, but sodium bicarbonate does not. It is possible that sodium-sensitive hypertension exhibits changes in blood pressure and in calcium metabolism based on the dietary chloride content.

Funding Source:
Industry:
National Dairy Board as adminstered by the National Dairy Council, Siemens Erben OHG, Mainz, Federal Republic of Germany
Commodity Group:
University/Hospital: General Clinical Research Center, Indianapolis, Indiana
Reviewer Comments:
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) 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")? N/A
4. Was method of handling withdrawals described? N/A
  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? Yes
  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? 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? 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? ???
  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? N/A
  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? ???
  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)? No
  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