HTN: Minerals (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To isolate and evaluate the effect on blood pressure of a modest increase in dietary potassium.
Inclusion Criteria:
  • Healthy volunteers
  • Subjects were interviewed about their general health conditions, smoking habits, alcohol consumption, use of medications and physical activity
  • Those already taking vitamin and mineral supplements were allowed to participate with the provision that they continued to use them.
Exclusion Criteria:
  • Diseases or conditions that might involve collateral effects from potassium supplementation or interfere with its metabolism (IDDM, NIDDM, diabetes insipidus, cardiovascular diseases or previous cardiovascular events, any kind of renal disease, metabolic acidosis, current peptic ulcers, dysphagia, general digestive problems, gastric surgery, pregnancy and lactation)
  • Use of anti-hypertensive drugs
  • Use of drugs known to interfere with potassium metabolism.
Description of Study Protocol:
  • Recruitment: Subjects recruited from amongst the academic and post-graduate research staff
  • DesignRandomized controlled trial
  • Blinding used: Double-blind
  • Intervention: Subjects randomized to receive 24mmol per day of potassium, approximating the content of five portions of fruits and vegetables or a placebo for six weeks. Randomization through computer generated code.

Statistical Analysis

  • For interval level variables, differences between groups were tested using the two-sample T-test, while differences within each group were tested with the paired T-test
  • For ordinal level variables, tests were performed with Mann-Whitney U-test and the Wilcoxon signed rank test for comparisons between and within the two groups, respectively
  • The chi-squared test was used to assess the significance of differences between the groups for nominal level variables
  • Correlations between the different variables and blood pressure were initially tested using a stepwise regression analysis. Thereafter, a regression analysis was performed, based on the variables present in the final stepwise model.
  • Variables that were found to be correlated with baseline blood pressure were included as covariates in a repeated-measurement ANOVA.
Data Collection Summary:

Timing of Measurements

  • Measures of blood pressure, anthropometric characteristics and urine analysis for electrolytes were recorded during a one-week baseline period
  • Blood pressure and body weight measured every three weeks during the six-week study period and a 24-hour urine sample collected during final week.

Dependent Variables

  • Change in mean arterial pressure calculated
  • Systolic and diastolic blood pressure assessed at same time of day to avoid influence of circadian variations
  • Instructed not to smoke, exercise, eat or drink 30 minutes prior
  • Urinalysis of Na, K and chloride analyzed by flame photometry. 

Independent Variables

  • Randomized to receive 24mmol slow-release potassium chloride (one eight-mmol tablet three times a day with meals) or placebo
  • Adherence assessed at each visit by interview and counting pills returned.

Control Variables

  • BMI
  • Age.
Description of Actual Data Sample:
Initial N
  • 71 subjects originally recruited for study

  • 36 in KCl group

  • 35 in placebo.

Attrition (final N)

  • 59 volunteers
  • 30 in KCl group (53% women)
  • 29 in placebo group (35% women)
  • 17% dropout rate
  • Subjects who changed their usual diet or other general lifestyle factors known to influence blood pressure were excluded.

Age

  • KCl group: Mean, 44.5±2.1 years
  • Placebo group: Mean, 41.7±2.2 years.

Ethnicity

  • KCl group: 83% European, 7% Middle-Eastern, 3% South Asian, 7% East Asian
  • Placebo group: 83% European, 7% Middle Eastern, 7% South Asian, 3% East Asian. 

Anthropometrics

  • There were no significant differences between groups with regard to age, BMI, urinary electrolyte excretion, Na:K, blood pressure levels, heart rate, degree of physical activity and smoking habit
  • The KCl group contained more females than the placebo group, but these differences were not statistically significant.

Location

United Kingdom.

Summary of Results:

 

Potassium (N=30)

Placebo (N=29)

Mean Difference 95% CI
Week Zero to Three MAP -2.21±0.72 1.13±0.80 -3.34 -5.22, -1.47

Week Zero to Three SBP

-0.98±1.20

0.30±0.83

-1.28

-4.21, 1.65

Week Zero to Three DBP

-2.53±0.73

1.58±0.66

-4.11

-6.09, -2.13

Week Three to Six MAP -2.70±0.91  0.96±0.59 -3.66 -5.84, -1.49
Week Three to Six SBP -5.23±1.00 1.08±0.73 -6.32 -8.84, -3.79
Week Three to Six DBP -1.48±4.91 0.87±0.65 -2.35 -4.70, 0.00
Week Zero to Six MAP -4.91±0.79 2.09±0.69 -7.01 -9.12, -4.89
Week Zero to Six SBP -6.22±1.10 1.38±0.95 -7.60 -10.46, -4.73
Week Zero to Six DBP -4.02±0.87 2.45±0.73 -6.46 -8.74, -4.19

Other Findings

  • Compliance to treatment was 89% for the KCl group and 83% for placebo, difference was not statistically significant
  • In neither of the groups did BMI or heart rate change significantly during the course of the investigation, nor was there a significant difference between the two groups
  • In the placebo group, MAP significantly increased
  • After six weeks of supplementation, MAP was reduced by 7.01mm Hg (95% confidence interval: -9.12 to -4.89, P<0.001)
  • SBP was reduced by 7.60mm Hg (95% confidence interval: -10.46 to -4.73, P<0.001)
  • DBP was reduced by 6.46mm Hg (95% confidence interval: -8.74 to -4.19, P<0.001)
  • The reduction in MAP was positively associated with baseline urinary Na:K (P<0.034)
  • Using BMI and age as covariates, the groups had significantly different changes in blood pressure (P=0.001).
Author Conclusion:

A low daily dietary supplement of potassium, equivalent to the content of five portions of fresh fruits and vegetables, induced a substantial reduction in MAP, similar in effect to single drug therapy for hypertension.

Funding Source:
Reviewer Comments:
  • 17% dropout rate, but only due to change of diet and lifestyle
  • Compliance was high.
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? 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? 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? Yes
  6.6. Were extra or unplanned treatments described? Yes
  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)? N/A
  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