EAL

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 of the study was to compare the effects of long-term daily supplementation with 10mmol of potassium and 10mmol of calcium on the blood pressures, sodium metabolism and urinary excretion of salt-sensitive children with that of children who were not salt-sensitive.

Inclusion Criteria:

Children of approximately 10 years of age in grades three and four in a primary school in Hanzhong, China.

Exclusion Criteria:

Children were excluded from participating for any of the following conditions:

Secondary hypertension
History of cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, and other chronic diseases
Serum creatinine of 1.7mg per dL or more at screening exam
Inability or unwillingness to participate in all aspects of study.

Description of Study Protocol:

Recruitment

Children from six third grade and fourth grade classes from a primary school in Hangzhou, China were recruited
Researchers met with the children, their parents and teachers to explain the program and protocol. Children with their guardian's consent signed an informed consent.
The children were assigned to the intervention or control group by means of class cluster sampling and randomization.

Design

Randomized control trial.

Blinding Used

Double-blinded trial: Both children and those collecting data were blinded to their group assignment,

Intervention

Daily supplementation with 10mmol of potassium and 10mmol of calcium for two years.

Statistical Analysis

ANOVA, paired and unpaired T-tests, chi-squared test and Fisher's exact test.

Data Collection Summary:

Timing of Measurements

Blood pressure was measured at baseline and at two years
Sodium, potassium and calcium urinary excretion was determined at baseline and at two years
Salt sensitivity was measured at the end of the two-year intervention by means of a volume expansion and contraction protocol.

Dependent Variables

Blood pressure was measured in the right arm of the children using Hawksley random zero sphyngmomanometers. First and fourth phase Korotkoff sounds were designated as SBP and DBP, respectively. After a five-minute seated rest, a total of three measurements were taken. An average of three readings was reported.
Sodium, potassium and calcium urinary excretion was determined by collecting a 24-hour urine sample. The sample was analyzed.

Independent Variables

Salt sensitivity was measured by means of a volume expansion and contraction protocol
Calcium and potassium supplementation vs. no supplementation.

Control Variables

Participants were told to maintain their usual diet. This diet was described as high in salt.

Description of Actual Data Sample:

Initial N

308 children were screened for participation
One was excluded for secondary hypertension and six were rejected for reasons not specified
301 children were enrolled in the study.

Attrition (Final N)

33 children left school or transferred; seven could not complete the salt-sensitivity determination
261 completed the study (128 boys and 133 girls), with an 87% follow-up rate.

Age

The children were all about 10 years old. There was no significant difference in age between the intervention and placebo group.

Ethnicity

No discussion in the study; assumed to be Chinese.

Other Relevant Demographics

There was no significant difference between the intervention and placebo group in terms of gender.

Anthropometrics

There was no significant difference between the intervention and placebo group in terms of height, weight, BMI, blood pressure or heart rate at baseline. Nor was there any significant difference in the rate of change in height, weight or BMI over the two years of the study between the intervention and placebo group.

Location

A primary school in Hangzhou, China.

Summary of Results:

Key Findings

21.5% of the 261 children were found to be salt-sensitive.

Increase in Blood Pressure with Two-Year Potassium and Calcium Supplementation for Salt-sensitive and Non-Salt-Sensitive Children

Salt-sensitive children who took the supplement had a lower increase in blood pressure over the two years than those who did not. A significant difference was not observed in the two groups in non-salt-sensitive children.

Variables		Intervention Group Measures and Confidence Intervals	Placebo Group Measures and Confidence Intervals	Statistical Significance of Group Difference
Salt-Sensitive	Systolic BP	1.4±8.5	5.7±8.1	P<0.05
Salt-Sensitive	Diastolic BP	1.8±8.4	6.6±7.9	P<0.05
Non-Salt-Sensitive	Systolic BP	3.7±8.9	5.1±8.4
Non-Salt-Sensitive	Diastolic BP	4.4±7.3	5.7±8.1

24-Hour Potassium Excretion at Baseline and at Two Years

Both salt-sensitive and non-salt-sensitive children who took the supplement had a higher potassium excretion at the end of the two-year intervention than those who did not.

Variables	Intervention Measures and Confidence Interval	Placebo Group Measures and Confidence Interval	Statistical Difference Between Intervention and Placebo
Salt-Sensitive Baseline	4.1±3.4	3.8±2.4
Salt-Sensitive End Point	4.8±2.3	3.9±2.8	P<0.05
Non-Salt-Sensitive Baseline	4.0±3.3	4.4±2.9
Non-Salt-Sensitive End Point	4.8±2.4	3.9±2.4	P<0.05

24-Hour Sodium Excretion at Baseline and at Two Years

Sodium excretion increased significantly between baseline and the end of the two-year intervention in salt-sensitive children who took the supplement as compared to those who did not. A significant increase was not observed in either of the two groups of non-salt-sensitive children.

Variables		Intervention Group Measure and Confidence Interval	Placebo Group Measure and Confidence Interval	Statistical Difference Between Intervention and Placebo
Salt-Sensitive	Baseline	39.7±18.1	41.6±17.4
	End point	53.6±20.6	42.9±21.3	P<0.001
	Increased-value	13.0±21.1	1.3±22.7	P<0.001
Non-Salt-Sensitive	Baseline	43.9±20.3	42.5±20.1
	End point	49.0±21.3	45.4±20.3
	Increased value	5.4±23.8	2.8±21.7

Other Findings

There were no significant differences in calcium excretion between salt-sensitive and non-salt-sensitive children who took the supplement and those who did not.

Author Conclusion:

A long-term increase in potassium and calcium intake in salt-sensitive children can significantly reduce the age-related increase in blood pressure while such an effect is not found in non-salt-sensitive children
Long-term potassium and calcium supplementation appeared to promote the excretion of sodium in salt-sensitive children. This excretion is inversely associated with the BP increase seen in salt-sensitive children. This relationship was not seen in non-salt-sensitive children.

Funding Source:

University/Hospital:

Cardiovascular Research Institute of Xian Jiatong University

Reviewer Comments:

The socio-economic and ethnic characteristics of the study population were not described, particularly with regards to whether they were typical of the region or nation
The sodium, potassium and calcium content of the children's diet was not determined or controlled
Salt sensitivity was determined only at the end of the intervention. There was no discussion of whether the intervention might have reduced the prevalence of the expression of salt sensitivity. The study by Ye T, Liu Z et al, 2003, showed some changes in salt-sensitivity amongst Chinese teenagers over five years with no intervention.
The follow-up rate of 87% was exceptionally strong for such a long study. There was, however, no discussion of how the withdrawal rate compared between the intervention and placebo group.

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?	???
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?	???
	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?	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
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	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?	???
	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)?	N/A
	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?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	???
	10.2.	Was the study free from apparent conflict of interest?	Yes