• Increase Font Size
  • Decrease Font Size
  • View as PDF

HTN: Sodium (2015)

Citation:

He FJ, Li J, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ. 2013; 346: f1325.

PubMed ID: 23558162
 
Study Design:
Meta-analysis or Systematic Review
Class:
M - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To determine the effects of moderate, longer-term salt reduction on blood pressure, plasma lipids and hormones. This effect was further examined by blood pressure status, sex and ethnic group.
Inclusion Criteria:
  • Trials included randomization to either a control (usual salt intake) or intervention (moderately reduced salt intake) group
  • Reduction in 24-hour urinary sodium within the range of 40mmol to 120mmol (equal to 2.3g to 7.0g per day salt)
  • Duration of salt reduction four or more weeks
  • Age more than 18 years
  • Individuals could have hypertension.
Exclusion Criteria:
  • Concomitant interventions including non-pharmacological interventions, anti-hypertensive or other medications in both groups
  • Children
  • Pregnant women
  • Individuals with diabetes or heart failure.
Description of Study Protocol:

Recruitment

  • Search strategy included the following electronic databases:
    • Medline (1950 to November 2012)
    • Embase (1980 to November 2012)
    • Hypertension Group Specialised Register
    • Cochrane Central Register of Controlled Trials.
  • Reference lists were reviewed for original and review articles
  • No language restrictions.

Design

  • Data was extracted using a standard form by two of the authors. Differences were resolved by discussion with the third author.
  • Study quality was assessed with the following criteria:
    • Group allocation was judged adequate or inadequate:
      • Adequate: Central randomization or other method where participants and investigators could not foresee assignment
      • Inadequate: Open list of random numbers or other method where participants and investigators could determine assignment.
    • Blinding:
      • Double blind
      • Observer blind to blood pressure
      • Open study.
    • Completeness of follow-up:
      • Intention to treat vs. non-intention to treat
      • Number of participants lost to follow-up after randomization.
Statistical Analysis
  • Treatment effect for outcomes was determined:
    • Crossover trials: Difference between the end of the intervention and control periods
    • Parallel trials: Difference between the two treatment groups from baseline to end of follow-up.
  • Variance of the treatment effect for outcomes was calculated for each trial using:
    • Standard deviations or standard errors
    • Confidence intervals and exact T-test or P values
    • Imputed by inverting a boundary P value (e.g., P<0.05 became P=0.05) or assuming a correlation coefficient of 0.5 between the initial and final measurement.
  • Mean effect sizes were estimated using pooled data and the inverse variance method in random effects meta analysis
  • Heterogeneity  was assessed with the I2 test (I2 more than 50% was considered significant); the source of heterogeneity was examined with meta regression analysis
  • Relationship between the change in 24-hour urinary sodium and the change in blood pressure was evaluated with meta regression analysis
  • Funnel plot asymmetry assessed publication bias and Egger's regression test estimated funnel plot asymmetry
  • Sub-group analyses:
    • Groups were further divided by blood pressure status, sex and ethnicity
    • If more than 85% of the participants in a trial were white, then the ethnic group was considered white
    • If information on ethnic group was not provided, the study was excluded from this sub-group analysis
    • Not performed for lipid and hormone data due to the small number of trials reporting these outcomes.
Data Collection Summary:

Timing of Measurements

  • Extracted data included:
    • Characteristics of the study
    • Design:
      • Crossover
      • Parallel.
    • Type of blinding:
      • Open
      • Single blind
      • Double blind.
    • Randomization method
    • Method of blinding:
      • Placebo
      • Random zero or automated sphygmomanometers
      • Observer blind to blood pressure
      • Open.
    • Study duration:
    • Results before and after intervention
    • Changes in systolic and diastolic blood pressure
    • Twenty-four hour urinary sodium excretion
    • Lipids:
      • Total cholesterol
      • LDL cholesterol
      • HDL cholesterol
      • Triglycerides.
    • Hormones:
      • Plasma renin activity
      • Aldosterone
      • Noradrenaline
      • Adrenaline.
    • Statistics that could be used to estimate the variance of the outcome measures.

Dependent Variables

  • Primary: Blood pressure:
    • Trials with normotensive individuals
    • Trials with hypertensive individuals
    • All trials.
  • Secondary:
    • Lipids
    • Hormones
    • Study quality
    • Publication bias.

Independent Variables

Moderate salt reduction vs. usual salt intake.
 
Description of Actual Data Sample:

Initial N

  • All: N=34 trials (30 trials, in which four trials included both normotensive and hypertensive individuals, so each counted as four separate trials), for a total of 3,230 participants:
    • Hypertensive: N=22 studies (990 participants)
    • Normotensive: N=12 studies (2,240 participants).
  • Sex:
    • Men:
      • Hypertensive: N=9 or 10 studies, depending on outcome (227 to 239 participants)
      • Normotensive: N=6 studies (1,391 participants).
    • Women
      • Hypertensive: N=9 or 10 studies depending on outcome (181 to 193 participants)
      • Normotensive: N=6 studies (691 participants).
  • Hormone trials:
    • Plasma renin: N=14 studies (455 participants)
    • Aldosterone: N=9 studies (340 participants)
    • Noradrenaline: N=6 studies (129 participants)
    • Adrenaline: N=4 studies (84 participants).
  • Lipid trials:
    • Total cholesterol: N=8 studies (365 participants)
    • LDL cholesterol: N=5 studies (262 participants)
    • HDL cholesterol: N=6 studies (278 participants)
    • Triglycerides: N=6 studies (309 participants).

Attrition (Final N)

N=34.

Age

Median 50 years (range 22 years to 73 years):

  • Hypertensive individuals: Median age 50 years (range 24 years to 73 years)
  • Normotensive individuals: Median age 50 years (22 years to 67 years).

Ethnicity

  • White:
    • Hypertensive: N=16 or 17 studies depending on the outcome (599 participants)
    • Normotensive: N=12 studies (1,901 participants).
  • Black:
    • Hypertensive: N=5 studies (171 participants)
    • Normotensive: N=3 studies (412 participants).
  • Asian:
    • Hypertensive: N=1 studies (29 participants)
    • Normotensive: N=0 studies.

Other Relevant Demographics

  • Median blood pressure: 148/93mm Hg
    • Hypertensive: 148/93mm Hg
    • Normotensive: 127/77mm Hg.
  • Median 24-hour urinary sodium: 160mmol (range 125mmol to 200mmol) equivalent to salt intake of 9.4g per day (range 7.3g to 11.7g per day)
    • Hypertensive: 162mmol (range 125mmol to 191mmol) equivalent to salt intake of 9.5g per day (range 7.3g to 11.7g per day)
    • Normotensive: 153mmol (range 128mmol to 200mmol) equivalent to salt intake of 8.9g per day (range 7.5g to 11.7g per day).
  • Median study duration: Four weeks (range four weeks to three years)
    • Hypertensive: Five weeks (range four weeks to one year)
    • Normotensive: Four weeks (range four weeks to three years).

Location

  • Queen Mary University, London, UK
  • Affiliated Hospital of LuZhou Medical College, Luzhou, Sichuan, China.

 

Summary of Results:

 

Key Findings
 

Variables All Trials 
Mean (range)		 Hypertensive Trials
Mean (range)		 Normotensive Trials
Mean (range)
Change in 24-hour urinary sodium, mmol -75 (-40 to -118) -4.4 (-3.1 to -6.8) -4.4 (2.3 to -6.9)
Reduction in salt intake, g per day - 4.4 (-2.3 to -6.9) -4.4 (-3.1 to -6.8) -4.4 (2.3 to -6.9)
Change in systolic blood pressure, mm Hg -4.18
95% CI: -5.18 to -3.18, P<0.001
I2=75%		 -5.39 
95% CI: -6.62 to -4.15
P<0.001
I2=61%		 -2.42
95% CI: -3.56 to -1.29
P<0.001
I2=66%
Change in diastolic blood pressure, mm Hg -2.06 
95% CI: -2.67 to -1.45
P<0.001
I2=68%		 -2.82
95% CI: -3.54 to -2.11
P<0.001
I2=52%		 -1.00
95% CI: -1.85 to -0.15
P=0.02
I2=66%

 

Source of Heterogeneity

  • All trials:
    • Change in 24-hour urinary sodium, age, blood pressure status and ethnic group (regression analysis) were significantly associated with the reduction in systolic blood pressure accounting for 68% of the variance between studies
    • After adjusting for age, blood pressure status and ethnic group, a 100mmol reduction in 24-hour urinary sodium (equivalent to 6g per day of salt) resulted in a reduction of 5.8mm Hg (95% CI: 2.5 to 9.2; P=0.001) in systolic blood pressure
    • Age, ethnic group, blood pressure status and 24-hour urinary sodium accounted for 41% of the variation in diastolic blood pressure between studies; however, only ethnic group was significantly associated with changes in diastolic blood pressure (P=0.021).
  • Trials with hypertensive individuals:
    • Change in 24-hour urinary sodium and ethnic group were significantly associated with reduced systolic blood pressure. Including age with these two variables accounted for 46% of the variance between studies.
    • After adjustment for age and ethnic group, a 100mmol reduction (6g per day of salt) in 24-hour urinary sodium resulted in a 10.8mm Hg (3.5 to 18.2, P<0.01) decrease in systolic blood pressure
    • None of the variables (24-hour urinary sodium, ethnic group, age) were significantly related to the decrease in diastolic blood pressure. These variables explained 11% of the variation between studies.
  • Trials with normotensive individuals:
    • Three variables (age, ethnic group, change in 24-hour urinary sodium) accounted for 51% of the variation seen in systolic blood pressure between studies; however, only change in 24-hour urinary sodium was significant associated with a decrease in the systolic blood pressure
    • Systolic blood pressure was reduced 4.3mg Hg (95% CI: 0.1 to 8.5, P<0.05) with a 100mmol reduction in 24-hour urinary sodium (6g per day of salt)
    • Age, ethnic group and change in 24-hour urinary sodium accounted for 43% of the variation in diastolic blood pressure between studies; only ethnic group was significantly associated with a decrease in diastolic blood pressure (P=0.04).
Additional Sub-group Analyses

 
  Hypertensive Men Normotensive Men Hypertensive Women Normotensive Women
Change in 24-hour urinary sodium, mmol -86.07
95% CI: -100.17 to -71.97
P<0.001		 -67.26
95%CI: -81.90 to  -52.62
P<0.001		 -69.56
95% CI:         -77.56 to -61.55
P<0.001		 -62.98
95% CI:         -88.59 to -37.37
P<0.001
Reduction in salt intake, g per day -5.04
95% CI: -5.86 to -4.21		 -3.93
95% CI: -4.79 to -3.08		 -4.07
95% CI: -4.54 to -3.60		 3.68
95% CI: -5.18 to -2.19
Change in systolic blood pressure, mm Hg -6.4
95% CI: -8.00 to -4.80
P<0.001		 -3.39
95% CI: 5.63 to -1.16
P=0.003		 -3.39
95% CI: -5.63 to -1.16
P<0.001		 -4.26
95%CI: -88.59 to -37.37
P<0.001
Change in diastolic blood pressure, mm Hg -3.96
95% CI: -5.47 to -2.46
P<0.001		 -1.78 
95% CI: -3.01 to -0.55
P=0.005		 -2.18
95% CI: -2.95 to -1.41
P<0.001		 -2.18
95% CI: -2.95 to -1.41
P<0.001
 
  Hypertensive Blacks Normotensive Blacks Hypertensive Whites Normotensive Whites
Change in 24-hour urinary sodium, mmol -66.87
95% CI: -82.79 to -50.95
P<0.001		 -40.31
95% CI: -97.16 to 16.55
P=0.16		 -77.46
95% CI: -85.22 to -69.66
P<0.001		 -76.45
95% CI: -89.52 to -63.38
P<0.001
Reduction in salt intake, g per day -3.91 
95% CI: -4.84 to -2.98		 -2.36 
95% CI: -5.68 to 0.97		 4.53
95% CI: -4.99 to -4.08		 -4.47
95% CI: -5.24 to -3.71
Change in systolic blood pressure, mm Hg -7.83
95% CI: -10.96 to -4.7
P<0.001		 -4.02
95% CI: -7.44 to -0.61
P=0.02		 -5.12
95% CI: -6.27 to -3.96
P<0.001		 -2.11
95% CI: -3.03 to -1.19
P<0.001
Change in diastolic blood pressure, mm Hg -4.08
95% CI: -5.90 to -2.26
P<0.001		 -1.98
95% CI: -4.45 to 0.49
P=0.12		 -2.66
95% CI: -3.37 to -1.95
P<0.001		 -0.88
95% CI: -1.68 to -0.08
P=0.03

 

Effect of Salt Reduction on Hormones
 

  Change 95% CI P value
Plasma renin activity, ng per ml per hour 0.26 0.17 to 0.36 <0.001
Aldosterone, pmol per ml 73.20 44.92 to 101.48 <0.001
Noradrenaline, pmol per ml 187 39 to 336 0.01
Adrenaline, pmol per L 37 -1 to 74 0.06

 

Effect of Salt Reduction on Lipids

No significant changes in plasma lipid levels were observed relative to reduced 24-hour urinary sodium.

Study Quality

  • Randomization:
    • N=26 (with adequate concealment)
    • N=8 (not reported).
  • Intention to treat:
    • Intention to treat analysis: Seven trials
    • A total of 6.7% participants were lost to follow up following randomization.
  • Blinding:
    • Double blind: N=22
    • Observer blind: N=11
    • Open: N=1.

Publication Bias

  • Systolic blood pressure:
    • Funnel plot was asymmetrical around effect size, indicating bias (P=0.025)
    • With removal of two larger and long-term studies, asymmetry test was no longer significant (P=0.247).
  • Diastolic blood pressure: Funnel plot was symmetrical around effect size (P=0.416).

Other Findings

  • Study design:
    • Crossover: N=23
    • Parallel: N=12.
  • Blinding:
    • Double blind: N=22
    • Observer blind: N=11
    • Not reported: N=1.
  • Study duration:
    • Hypertensive trials:
      • Four weeks: N=10
      • Five weeks: N=2
      • Six weeks: N=3
      • Eight weeks: N=5
      • Twelve weeks: N=1
      • Six months: N=1
      • Twelve months: N=1.
    • Normotensive trials:
      • Four weeks: N=9
      • Six weeks: N=3
      • Eighteen months: N=1
      • Thirty-six months: N=1.
Author Conclusion:
  • A moderate reduction in salt intake (4.4g per day) will have a significant effect on blood pressure in hypertensive and normotensive individuals as well as men, women, white and black participants
  • Results support a dose response relationship:A larger reduction in salt intake will result in a greater decrease in blood pressure
  • Target population salt intake should be 3g per day.
Funding Source:
University/Hospital: Queen Mary University, London; Affiliated Hospital, LuZhou Medical College, Luzhou Sichuan, China
Reviewer Comments:
  • No search terms were described
  • The median study duration was only four weeks, which was short-term.
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? No
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes