Disorders of Lipid Metabolism and Micronutrients

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

To investigate the reproducibility of salt sensitivity testing using a dietary approach. 

Inclusion Criteria:

Patients referred to the outpatient hypertension clinic for 24-hour ambulatory blood pressure (BP) monitoring.

Exclusion Criteria:
  • Low dietary compliance, confirmed by their daily Na excretion
  • Diastolic BP of more than 120mm Hg, requiring hypertensive medication.
Description of Study Protocol:

Recruitment

Patients referred to the outpatient hypertensive clinic for 24-hour ambulatory BP monitoring.

Design

Diagnostic study, crossover design.

Intervention

Six-day-long salt depletion period with diet containing 50mmol Na per day (3.0g per day) followed by a six-day-long salt repletion period when patients returned to their habitual diet and added 150mmol (9.0g) of NaCl per day given as sodium chloride tablets (SlowSodium 600 mg, Ciba Geigy, West Sussex, UK). 

Statistical Analysis

  • SPSS for Windows version 6.0 statistical computing program
  • Altman-Bland method used to assess the reproducibility of BP response to change in dietary salt intake.

 

Data Collection Summary:

Timing of Measurements

  • Casual as well as 24-hour ambulatory BP were recorded:
    • On habitual diet
    • After six days of dietary salt restriction
    • After six days of salt repletion
  • Blood and 24-hour urine samples were collected during each of these periods for measurement of erythrocyte volume fraction (EVF), plasma and blood volume, serum creatinine and urinary Na, and creatinine excretion.

Dependent Variables

  • 24-hour ambulatory BP recorded using Accutracker II monitor. The monitor was programmed to measure BP every 20 minutes between 6:00 A.M. and 10:00 P.M. and every 30 minutes between 10:00 P.M. and 6:00 A.M.  
  • Casual BP was measured by the same method by the same investigator after completion of the 24-hour ambulatory BP recordings using a Hg sphygmomanometer. Three measurements performed in a sitting position after five minutes of rest with one-minute intervals. The mean of the last two recordings was listed as casual BP 
  • SS defined as an increase of more than 10% mean BP (modified Bartter's definition of SS: Kawasaki et al, 1978) when changing from a low- to high-dietary salt intake (from 50 to 250mmol Na per day). 

Independent Variables

 Daily dietary Na intake was assessed using 24-hour urinary Na excretion.

  

Description of Actual Data Sample:
  • Initial N: 48 
  • Attrition (final N): 30 (seven females and 23 males)
  • Age: 43±9 years (range 24 to 61 years)
  • Ethnicity: Norwegian.

Anthropometrics

  • All patients had a casual diastolic blood pressure (DBP) of more than 90mm Hg and were working
  • Mean duration of hypertension was 4.0+3.0 years
  • Mean serum creatinine was 96+13mcmol per L
  • Mean BMI was 27.7kg/m2

Location

Bergen, Norway.

 

Summary of Results:

Total Population 

  • No significant correlation between urinary Na excretion and casual or 24-hour BP found at any of the three levels of Na intake
  • Body weight decreased by about 1.0kg during salt depletion and increased by 1.0kg during salt repletion
  • Daily urinary excretion of K and creatinine did not differ within or between the two tests (94mmol, 93mmol and 92mmol per 24 hours and 14.2mmol, 14.9mmol and 13.6mmol per 24 hours, respectively, at baseline and low and high Na intake at the first test)
  • Baseline casual and 24-hour mean BP and daily Na excretion did not differ between first and second salt-sensitivity test (120 vs. 119mm Hg, 112 vs. 109mm Hg, and 163 vs. 142mmol per 24 hours)
  • Positive correlation between casual and 24-hour BP measured in the first and second test both at baseline, and after salt depletion and repletion, respectively (R=0.66 and 0.69 at baseline, R=0.70 and 0.76 after salt depletion, and R=0.70 and 0.72 salt repletion, all P<0.01)  
  • Correlation between baseline daily Na excretion in the two tests (R=0.48, P<0.01)
  • Change in daily Na excretion during salt depletion did not differ between the two tests (61mmol and 71mmol)
  • Reduction in casual and 24-hour mean BP during Na depletion differed between first and second test (8.0 and 6.0mm Hg in first test, and 4.0 and 2.0mm Hg in second test, P<0.05)
  • During salt repletion, average 24-hour Na excretion after six days did not differ in the two tests (266mmol and 261mmol)
  • No correlation found between change in casual or 24-hour mean BP during salt repletion in the first or second test (R=0.10, P=0.58)
  • No correlation found between month of the first test and casual or 24-hour BP, body weight, blood volume, daily Na excretion or change in BP or daily Na excretion during salt depletion or repletion.  

Salt Sensitivity Assessed by 24-hour BP

  • By defining salt sensitivity as a more-than 10% increase in 24-hour mean BP when changing from a low- to a high-dietary salt intake, eight patients (27%) were classified as salt sensitive and 22 as salt resistant in the first test
  • In the second test, three of eight patients initially classified as salt sensitive and 15 or the 22 patients initially classified as salt resistant maintained their salt sensitivity status
  • Thus, 18 patients (60%) had the same salt sensitivity on the two tests, but 40% did not.

Salt Sensitivity Assessed by casual BP

  • By defining salt sensitivity as a more-than 10% increase in casual mean BP during salt repletion, 13 patients (43%) were classified as salt sensitive and 17 as salt resistant in the first test
  • In the second test. three of 13 patients initially classified as salt sensitive and 13 or the 17 patients initially classified as salt resistant maintained their salt-sensitivity status
  • Thus, 16 patients (53%) had the same salt sensitivity on the two tests, but 47% did not.

 

 

 

Author Conclusion:

Casual and 24-hour BP response to a 200mmol per 24-hour increase in dietary salt intake is highly individual and varies over time. Characteristics of salt sensitivity using a dietary approach in outpatients has a poor reproducibility and the clinical value of this test in evaluation of hypertensive patients and their treatment is questionable.

Funding Source:
University/Hospital: Department of Heart Disease, Haukeland Hospital, Bergen, Norway
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
  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
  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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.1. 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
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? 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
  2.1. 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
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? 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? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
  3. Were study groups comparable? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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? ???
  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? ???
  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.) ???
  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.) ???
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? Yes
  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. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? 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
  4.2. 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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? 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
  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? N/A
5. Was blinding used to prevent introduction of bias? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) No
  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.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? 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
  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. 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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  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
  6.3. 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
  6.4. 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments 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
  6.7. 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
  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. 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
  7.1. 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
  7.2. 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
  7.3. 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
  7.4. 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
  7.5. 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
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? 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. 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
  8.1. 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
  8.2. 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
  8.3. 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
  8.4. 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
  8.5. 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
  8.6. 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? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? 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. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? No
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes