EAL

NA: Sodium or Sodium Chloride (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess the effect of a low- vs. high-sodium diet on blood pressure (BP) in normotensive Indo-Asian adults.

Inclusion Criteria:

Normotensive adults
40 years of age and older
Systolic blood pressure (SBP) less than 140mmHg
Diastolic blood pressure (DBP) less than 90mmHg
Not under antihypertensive medication.

Exclusion Criteria:

History of diabetes mellitus or fasting blood sugar of 126mg per dL or more
Kidney disease: Serum creatinine of 2.4mg per dL or more
Pregnant or lactating.

Description of Study Protocol:

Recruitment

Individuals were randomly selected from a computer-generated list of eligible participants in a separate hypertension screening study.

Design

At screening, socio-demographic data were collected by questionnaire; blood pressure, height and weight were measured; fasting blood samples were taken to measure glucose and creatinine levels
Randomized, controlled, crossover trial with 200 normotensive subjects, randomly selected from the general population in Karachi, Pakistan
Participants were randomly assigned to either a low-sodium (20m Eq per day) or a high-sodium diet (220m Eq per day) for one week, followed by a washout, then the alternate diet for one week
- Diets were created by nutritionist using culturally acceptable foods
- All meals were prepared in nutrition kitchen and delivered to participants daily
- Except for sodium content, there was no difference in meals between study groups.
Compliance was confirmed by 24-hour urinary sodium.

Blinding

Assessors masked to randomization status.

Intervention

Low-sodium (20m Eq per day) or a high-sodium diet (220m Eq per day) for one week, followed by a washout, then the alternate diet for one week.

Statistical Analysis

Data analysis done by SPSS 14.0 (SPSS, Chicago, IL) and SAS 9.1.3 (SAS Institute, Cary, NC)
Power calculations done
Paired T-tests
Generalized linear model
Mixed model procedures
Multivariable model.

Data Collection Summary:

Timing of Measurements

All measurements were performed to a standard protocol that conforms to the international standards for definitions and measurements
At screening, BP, height and weight were measured and fasting blood samples were taken for measuring glucose and creatinine levels
The distinction between hypertensive and normotensive individuals was made by measuring BP on two separate visits with an interval of at least a week
Three consecutive readings of BP were taken 20 minutes apart and the mean of final two readings was used for analyses
During study, compliance was confirmed by 24-hour urinary sodium and urinary creatinine at baseline and at the end of each intervention week
- 24-hour urinary sodium: Cx-7 Synchron Backman Analyzer by Ion Electrode (Aluminum Silicate)
- Urinary creatinine: Jaffe Rate method (Alkaline Picrate assay).
SBP measured at the end of high and low-sodium phases
All BP levels during follow-up were measured at least three days of each intervention and washout phase (days six, seven, 13, 14, 20 and 21)
BP measured 20 minutes apart with automated Omron monitor in sitting position at each visit and the mean of the final two readings on the last day of each intervention week was used in the analysis.

Dependent Variable

BP.

Independent Variable

Low- vs. high-sodium diet.

Control Variables

Timing of measurements
Crossover design.

Description of Actual Data Sample:

Initial N

240 randomly selected; 40 refused
200 participated: 95 men, 105 women.

Attrition (Final N)

184 participants (92%) completed the full duration of the trial.

Age

40 years of age and older
Mean age: 49.5±10.0.

Ethnicity

Indo-Asian; from the general population in Karachi, Pakistan.

Anthropometrics

Body mass index (BMI) (mean±standard deviation): 24.8±5.2.

Location

Karachi, Pakistan.

Summary of Results:

Baseline Characteristics

SBP approximately 122mmHg±11mmHg
Approximately 27% participants had high-normal baseline SBP (130mmHg to 139mmHg)
The mean (±standard deviation) baseline sodium excretion rate in all the participants and subset with high-normal SBP was 114.4mEq per day±51.6mEq per day and 110.2mEq per day±52.4mEq per day, respectively
Approximately 48% of the overall group and 50% of those in the high-normal baseline SBP group started intervention with high-sodium diet
The overall mean (95% confidence interval) decrease in SBP was 1mmHg (0mmHg to 3mmHg)] in the entire study population between the high- vs. low-sodium phase (P=0.17)
The decrease was more pronounced among those with high-normal SBP [6mmHg (2mmHg to 9mmHg)] (P=0.002) vs. those with normal SBP [-1mmHg (-2mmHg to 1mmHg)] (P=0.58) (P=0.001 for interaction)
No other baseline characteristics were significantly different among those who exhibited a decline vs. an increase in SBP
A significant change in the body weight [0.4kg (P=0.0002)] and BMI [0.2 (P=0.0003)] was also noted in the overall study population from high- to low-sodium diet
There was no carry-over effect from the first phase to the second phase (P=0.91)
The final multi-variable model for change in mean SBP including significant interaction between baseline SBP with change in dietary sodium (P=0.001) suggested that the decrease in SBP with change from high- to low-sodium diet was more pronounced by 6mmHg (2mmHg to 9mmHg)] among individuals with higher levels of baseline SBP
None of the other interactions were significant.

Author Conclusion:

Reducing sodium intake has a beneficial effect on blood pressure in Indo-Asians with high-normal SBP, at least in the short-term.
Given the ubiquity of high-normal blood pressure and frank hypertension in this population, we argue that primary prevention strategies, targeted at use of discretionary sodium, should now be designed and evaluated.

Funding Source:

Not-for-profit

Wellcome Trust Master's Research Training Fellowship award

Reviewer Comments:

This is a well-done study
Ethnic and dietary differences should be taken into consideration when comparing this to other studies conducted in more developed parts of the world.

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?	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
	3.1.	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
	3.2.	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
	3.3.	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?	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?	Yes
	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
	3.5.	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
	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.	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?	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.	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
	5.1.	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.)	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?	???
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	???
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	???
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	???
	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?	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
	6.2.	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?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments 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
	6.7.	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?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes