Reduced dietary salt for the prevention of cardiovascular disease
Systematic review summary
This document has been produced by the World Health Organization. It is a summary of findings and some data from the systematic review may therefore not be included. Please refer to the original publication for a complete review of findings.
Adler AJ, Taylor F, Martin N, Gottlieb S, Taylor RS, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No.: CD009217. DOI: 10.1002/14651858.CD009217.pub3.
- Few (8) trials were identified that met the inclusion criterion of a minimum of six months follow-up
- Reduced salt intake lowered systolic blood pressure in hypertensives and diastolic blood pressure in normotensives, but had no significant effect on all-cause or cardiovascular mortality
- When data from normotensives and hypertensives were combined, a 13% reduction in the risk of cardiovascular events was observed, although this was likely driven by a study in older adults living in residential care whereby kitchen staff prepared meals with a low sodium salt substitute
- Results of this analysis suggest dietary advice appears to have little effect on salt intake as measured by urinary sodium excretion, and strategies that do not require behaviour change may be more effective
1) To assess the long-term effects of advice and salt substitution, aimed at reducing dietary salt, on mortality and cardiovascular morbidity, and 2) to investigate whether a reduction in blood pressure is an explanatory factor in the effect of such dietary interventions on mortality and cardiovascular outcomes.
2. How studies were identified
The following databases were searched up to May 2013:
- CENTRAL (The Cochrane Library 2013, Issue 4)
- PsycINFO (up to October 2008)
- Health Technology Assessment (The Cochrane Library 2008, Issue4, not updated to 2013)
- Database of Abstracts of Reviews of Effects (The Cochrane Library 2008, Issue4, not updated to 2013)
Reference lists were also searched.
3. Criteria for including studies in the review
3.1 Study type
Randomized controlled trials and cluster-randomized trials with follow-up of at least six months
3.2 Study participants
Adults 18 years or over
(Studies in patients with heart failure, children or pregnant women were excluded)
(Studies in patients with heart failure, children or pregnant women were excluded)
Reduction of dietary salt intake either by provision of a low-sodium substitute or dietary advice from a health professional, compared to usual diet, control diet or placebo
3.4 Primary outcomes
- All-cause mortality
- Cardiovascular mortality
- Cardiovascular morbidity (fatal and non-fatal myocardial infarction, stroke, angina, heart failure, peripheral vascular events, sudden death, coronary artery bypass surgery, angioplasty with or without stenting, and cardiovascular-related hospital admissions)
3.5 Secondary outcomes
Secondary outcomes included changes in systolic and diastolic blood pressure, urinary salt excretion, health-related quality of life.
4. Main results
4.1 Included studies
Eight randomized controlled trials and cluster-randomized trials, enrolling 7284 participants, were included in this review.
- Three studies were in normotensive individuals, who were predominantly Caucasian and male, and had a median age of 40 years
- Two studies were in people with untreated hypertension and three were in mixed populations of both normo- and hypertensives individuals with a median age of 60 years, and most studies did not report ethnicity
- Follow-up ranged from six months post-randomisation to 15 years post-trial
- Two studies used salt substitution, one of which was performed by kitchen staff using potassium salt, and the other six studies involved dietary and behaviour change programmes
4.2 Study settings
- Australia, China, Hong Kong, Taiwan and the USA (4 studies)
4.3 Effect of intervention on primary outcomes
4.3.1 How the data were analysed
The reduction of dietary salt intake was compared with usual diet, a control diet or a placebo. Studies in mixed normo- and hypertensive populations were combined with those in hypertensive populations for analysis. For mortality and cardiovascular events, risk ratios (RR) and 95% confidence intervals (CI) were calculated, and for blood pressure and urinary sodium excretion, mean differences (MD) and 95% CI were calculated. Results were combined for the latest time point during the intervention and, as a secondary analysis, for the latest point available (including post-intervention follow-up).
Stratified meta-analysis was planned to explore the variation in effects that might occur due to: group versus individual advice, salt substitution versus advice, and baseline risk of cardiovascular disease. Meta-regression was planned to assess the relationship between the level of salt reduction achieved, baseline blood pressure, and change in blood pressure on mortality and cardiovascular event outcomes.
4.3.2 Summary of effects
There was no evidence of a decreased risk of death among those randomized to salt reduction in comparison to control in trials of normotensives (RR 0.67, 95% CI [0.40 to 1.12], p=0.13; 3 trials/3518 participants) or hypertensives (RR 1.00, 95% CI [0.86 to 1.15], p=0.95; 4 trials/3085 participants). This finding remained non-significant in pooled analysis across both participant populations (RR 0.96, 95% CI [0.83 to 1.10], p=0.55, 7 trials/6603 participants), and in analyses of the longest follow-up point in normotensives (RR 0.90, 95% CI [0.58 to 1.40] p=0.64; 3 trials/3518 participants, and hypertensives (RR 0.99, 95% CI [0.87 to 1.14], p=0.13; 5 trials/3680 participants).
Three trials in hypertensives contributed data to the pooled analysis of cardiovascular mortality, which showed a non-statistically significant 33% decrease in risk of cardiovascular death with salt reduction at the end of trial follow-up (RR 0.67, 95% CI [0.45 to 1.01], p=0.056; 3 studies/2656 individuals).
In trials of hypertensive individuals, reduced salt did not have a statistically significant effect on the risk of cardiovascular events at the end of trial follow-up (RR 0.76, 95% CI [0.57 to 1.01], p=0.06; 4 trials/3397 participants). Trials in both normotensives and hypertensives contributed data for analysis at the longest follow-up point, in which neither populations achieved a statistically significant reduction in the risk of cardiovascular events with a salt lowering intervention (RR 0.71, 95% CI [0.42 to 1.20], p=0.2; 2 trials/2505 participants and RR 0.77, 95% CI [0.57 to 1.02], p=0.068; 4 trals/3407 individuals, respectively). However, when the normotensive and hypertensive populations were considered together, pooled analysis resulted in a statistically significant 13% reduction in the risk of cardiovascular events in the treatment group relative to controls (RR 0.77, 95% CI [0.63 to 0.95], p=0.014; 6 trials/5912 participants).
Systolic blood pressure was not statistically significantly reduced in the treatment group compared to the control group in pooled analysis of normotensive trials. For hypertensive trials, however, there was a statistically significant benefit with salt reduction (MD -4.14 mmHg, 95% CI [-5.84 to -2.43], p<0.00001; 3 trials/1283 participants), as well as in pooled analysis across normotensive and hypertensive trials (MD -1.79 mmHg, 95% CI [-3.23 to -0.36], p=0.014; 6 trials/3362 participants), although this result had a substantial degree of heterogeneity (I2=74%). Meta-analysis demonstrated a statistically significant reduction in diastolic blood pressure among normotensives with salt lowering treatment (MD -0.80 mmHg, 95% CI [-1.37 to -0.23], p=0.0057; 3 trials/2079), but showed no evidence of an effect for hypertensives. Combined analysis across the two populations was statistically significant with an MD of -1.17 mmHg (95% CI [-2.08 to -0.26], p=0.012; 5 trials/2754 participants).
Urinary sodium excretion
Urinary 24-hour sodium excretion decreased similarly across all subgroups with salt lowering treatment, with an MD of -34.19 mmol/24 hours (95% CI [-49.61 to -18.78], p<0.0001; 3 trials/1812 participants) for normotensives; an MD of -20.48 mmol/24 hours (95% CI [-53.68 to 12.73], p=0.23; 3 trials/1235 individuals) for hypertensives, and an MD of -27.21 mmol/ 24 hours (95% CI [-49.85 to -4.57], p=0.019; 6 trials/3047 participants) in pooled analysis across all trials.
Health-related quality of life
One study reported statistically significant improvements in the Psychological General Well-Being scale in the treatment group relative to the control group, but no data were presented.
Subgroup and sensitivity analyses
Subgroup analyses were conducted excluding the trial that required kitchen staff in institutions rather than participants to employ potassium salt substitution. Its exclusion resulted in reductions in pooled effect sizes, as did excluding the two cluster-randomized trials in sensitivity analyses, except for in the overall pooled analysis of all-cause mortality where the effect size was non-significantly increased.
5. Additional author observations*
Despite strong public health advocacy encouraging salt reduction, the randomized evidence base is of insufficient power to provide conclusive answers regarding the effects of dietary advice and salt substitution on cardiovascular mortality and morbidity. In addition, the salt reduction achieved in the trials included in this review was relatively modest in its impact on urinary sodium excretion and blood pressure levels. Marked heterogeneity was observed across studies in terms of their population, sample size and follow-up, and only two of the eight included trials reported adequate random sequence generation, allocation concealment and outcome blinding.
Dietary advice appears to have limited effect on salt intake, as estimated by urinary sodium excretion, and on blood pressure. Therefore, alternative means of reducing salt intake may need to be implemented, such as sodium substitution in institutional and workplace kitchens in addition to regulatory approaches. Further trials are needed to assess these population-level interventions, which may prove to provide a more easily sustained, more practicable and less expensive means of reducing salt intake than individualized dietary advice.
*The authors of the systematic review alone are responsible for the views expressed in this section.