NA: Dietary Factors and Effect on Sodium and Blood Pressure (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The purpose was to compare the frequency of normotensive salt sensitivity in blacks vs. white subjects when potassium intake is suboptimal.

Inclusion Criteria:
  • Normotensive males
  • Not on medications
  • No history or clinical diagnosis of acute or chronic disease
  • Within 30% of ideal body weight.
Exclusion Criteria:

Not described.

Description of Study Protocol:

Recruitment

Not described.

Design

Randomized, controlled.

Blinding Used

Subjects were blinded as to whether the capsule contained potassium chloride or was a placebo. 

Intervention

The regular diet provided 15mmol of sodium, 30mmol of potassium and 14mmol of calcium per 70kg of body weight. Sodium chloride was loaded to the diet throughout the study, and potassium chloride supplements were administered.

Statistical Analysis

  • Analysis of variance (ANOVA)
  • Paired T-tests
  • Unpaired T-tests
  • Chi-square
  • Fisher exact test
  • Linear regression
  • SigmaStat software was used to perform data analysis.
Data Collection Summary:

Timing of Measurements

  • The total study time was six weeks. The first two weeks included the basal diet of 15mmol sodium, 30mmol of potassium and 14mmol of calcium per 70kg of body weight. During the last four weeks, 115mmol of sodium chloride was added to food and an additional 120mmol were given in capsules to be taken at every meal.
  • The last three weeks of salt loading had the subjects getting one of four regimens of potassium bicarbonate (KHCO3) in 10-mmol capsules.
  • Schedule A of potassium administration: (n=13) 40mmol of KHCO3 on days 21 to 28 and placebo on days 29 to 42
  • Schedule B of potassium administration: (n=13) 4 mmol of KHCO3 on days 21 to 42 and no placebo
  • Schedule C of potassium administration: (n=10, all black) 90mmol of KHCO3 on days 21 to 42 and no placebo
  • Schedule D of potassium administration: (n=5, all black) placebo on days 21 to 42, time controls
  • Blood pressure and weight were measured daily.

 Dependent Variables

  • Blood pressure was measured as the average of readings every four hours from 6:00 a.m. to 10:00 p.m. The readings were done at one-minute intervals, with the last four measurements averaged. Subjects had to remain supine for 15 minutes before the measurements and five minutes during the measurement, with no smoking or eating during this time and for 45 minutes prior to the readings.
  • Salt sensitivity was determined from a salt-induced mean arterial blood pressure (MAP) increase of ≥3mmHg. Subjects were categorized into moderate or severely salt-sensitive, based on a salt-induced increase of MAP.
  • Body weights were taken daily at 6:00 a.m.
  • Daily urine collection was performed to test for sodium, potassium, chloride, calcium and creatinine
  • Blood analysis was conducted on the last two days of each diet to measure sodium, potassium, chloride, total calcium, ionized calcium and creatinine.

Independent Variables

Salt restriction and salt loading dietary periods.

Description of Actual Data Sample:

Initial N

38 males.

Attrition (final N)

38 males.

Age

31 to 65 years.

Ethnicity

24 black, 14 white.

Other relevant demographics

Not described.

Anthropometrics

  • All subjects had normotensive blood pressure (systolic less than 140mmHg and diastolic less than 90mmHg.
  • None of the subjects were obese
  • Moderate salt sensitivity in 18 subjects (five white, 14 black)
  • Severe salt sensitivity in five subjects (all black).

Location

General Clinical Research Center at University of California, San Francisco Moffitt Hospital, San Francisco, CA.

Summary of Results:

Key Findings

Total urinary potassium excretion in all subjects was a strong predictor of changes in serum potassium (r=-0.58, P<0.001).

Based on ANOVA calculations, blood pressure in five black subjects was found to increase when potassium supplementation was stopped (P<0.05). High-normal potassium intake eliminated salt sensitivity in these five subjects.

Effects of increased potassium intake (changes in mean values shown as mean±SD)

  • Black subjects had a change in systolic blood pressure of -4.9mmHg±5.6mmHg (P<0.01), with -2.5mmHg±3.5mmHg for whites. Diastolic blood pressure in black subjects showed a change of -3.3mmHg±4.3mmHg (P<0.01), and white subjects had a change of -1.9mmHg±2.6mmHg.
  • MAP changed in black subjects by -3.9mmHg±4.5mmHg (P<0.01) and -2.1mmHg±2.7mmHg in white subjects.

Effects of salt-loading

  • Black subjects had a significant increase in systolic blood pressure, whereas white subjects did not
  • 79% of blacks were found to be salt-sensitive, compared with 36% of whites
  • A negative correlation was found between increase in body weight and overall increase in urinary excretion of sodium and chloride during salt loading (r=-0.41, P<0.01)
  • Results from all subjects showed that salt-induced changes in weight were significant predictors of increase in MAP (r=0.48, P<0.001)
  • When dietary potassium was 30mmol per day, normotensive black subjects had a significant increase in blood pressure after salt-loading, but normotensive white subjects did not. At this same level of potassium intake, a majority of normotensive black subjects had salt-sensitivity, and only a minority of normotensive white subjects were salt-sensitive. Additionally, one fourth of the black subjects had severe salt sensitivity, with none of the white subjects having this level of salt sensitivity.
Author Conclusion:

Potassium intake that is even slightly lower than the recommended amounts results in increased blood pressure in salt-sensitive, normotensive black males but not in normotensive white males. This level of potassium intake may affect the pressor response in salt-sensitive males.

Funding Source:
Government: National Institutes of Health
University/Hospital: Department of Medicine, General Clinical Research Center, University of California, San Francisco
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? ???
  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? 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? 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? 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? N/A
  6.6. Were extra or unplanned treatments described? No
  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? 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