Latin American and Caribbean Health Science Literature Database. - Reference lists of articles also reviewed for additional studies reviews found in the first phase were more than 2 years old). Reference of articles also reviewed for additional studies Inclusion criteria - Adults (18 years or older) with normal or raised blood pressure - Random allocation to either modestly reduced salt intake or usual salt intake (ie control) - Reduction in 24hr urinary sodium excretion must be within the range of 40 – 120mmol/24hr - Duration of salt reduction must have been for 4 or more weeks - Adults (16 years or older) - Randomised controlled clinical trials - Studies which were designed to reduce sodium intake, with a control group receiving either a placebo or no active intervention - Study duration of over 6 months -Individuals of all ages with normal or elevated blood pressure - Randomised controlled trials allocating participants to either a low or high sodium diet - Estimation of sodium intake by 24hr urinary sodium excretion (either by 24hr measurement or estimated from a sample of at 8 hours) - No restriction on study duration - Adults (16 and older) with normal or elevated blood pressure - Randomised controlled trials which compared reduced sodium intakes with usual or higher intakes - Healthy individuals as well as those with obesity, diabetes or chronic nephrolithiasis (kidney stones) - Co-interventions allowed if they were identical in the control and intervention groups - Duration of 4 or more - Reduction of sodium intake of >40mmol/day in intervention - Adults (16 years and older) with normal or elevated blood pressure - Included randomised controlled trials and prospective cohort studies - Studies included a quantitative measure of exposure (sodium intake) and compared this with an outcome of interest, or compared groups consuming different levels of sodium - Healthy individuals as well as those with obesity, diabetes or chronic nephrolithiasis (kidney stones) - Duration of 1 year or more - Reported on outcome of interest - Studies used FFQ, 24-hr recall, food record or urinary sodium excretion (included overnight and spot urine with appropriate validation) - RCTs, cohort, studies - studies in all ages, health statuses, races and ethnicities included trial trial trial
asymmetry was used to investigate publication bias. Separate were also conducted in specific sub-groupings, including pressure status (hypertensive or normotensive), ethnicity and sex. checked for heterogeneity by visual inspection and Cochran’s test. Random effects meta-regression was used to assess the effects of different factors such as initial SBP, ethnicity and sex etc. Sensitivity analyses were also conducted to assess the robustness of the data were conducted in different ethnicities. Assessment of heterogeneity was conducted using a chi-squared test included in the forest plot. Funnel plots were assessed for asymmetry. Sensitivity analysis was performed excluding studies giving rise to asymmetry in the funnel plots (<2g/day vs >2g/day, <1.2g/day vs > 1.2g/day and reduction relative to control), status of anti-hypertensive medication, duration, study design, type of blood pressure device used and method for measuring blood pressure. Sensitivity analysis conducted. outcome, sodium intake level in the reference group and the difference in sodium intake level between the reference and comparison group. Sensitivity analyses were also conducted. Critical appraisal system Summary tables were created, including relevant statistics which could be used in the pooled analysis. The risk of bias in included studies was evaluated (see below). The quality of the evidence for the effect of salt reduction on blood pressure was assessed using GRADE (ranked separately for all participants, Quality assessment of studies took into account randomisation procedure, allocation concealment, blinding of participants, providers of care and outcome assessors and losses to follow (using Cochrane Reviewer’s Handbook methodology) - GRADE system not used - Summaries of key points and data for each study were made by reviewers - Risk of bias evaluation conducted (see below) - GRADE system not used - Summaries of key points and relevant data for each study were made by reviewers - Risk of bias evaluation included (see below) - GRADE methodology used to assess the quality of the body of evidence - Summaries of key points and relevant data for each study were made by reviewers - Risk of bias evaluation included (see below) - methodology used to assess the quality of the body of evidence Rating system not used for individual studies (due to broad range of study designs and sodium intake assessments) Summary tables were developed to present details of designs, which were critically evaluated based on methodological appropriateness, relevance of study population, interventions and outcome measures
- was incomplete outcome data addressed: classified as ‘yes’ analysis used, all participants finished study or detailed information given on drop-outs), ‘unclear’ (no information given) or ‘no’ (not adequately addressed) analysis to adjust for possible confounding factors. Date of of last cited in review 2009 1998 2011 2010 2011 2012 Additional relevant Review noted large degree of inconsistency in methodological approaches used in studies
Angela Valenti (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results et al. (1984), Sweden [] parallel design study II Adult males (41 – 59 years), with hypertension (DBP: 95 - 105mmHg) Both groups were instructed to consume an energy restricted diet low in sodium. 1. provided with additional sodium via salt and sodium tablets 2. no sodium provided pressure (supine after 10 min rest) 23 9-11 weeks Low sodium diet: 97 +32 mmol/24hr Normal sodium diet: 200 + 56 mmol/24hr Mean difference between low sodium diet and normal sodium diet SBP: -8.40mmHg (CI: 4.27) DBP: -4.60mmHg (CI: -11.31, 2.11) Key features for bias assessment of randomised trials
Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Andersson et al. (1984) Unclear risk (no description of method of sequence generation) Unclear risk (no description of method of concealment of allocation) Participants: unclear risk Providers: high risk Outcome assessors: unclear risk 0% (low risk) Not required (low risk) No (low risk) Yes (low risk) Swedish National Association Against Heart and Chest Diseases, Goteborg Medical Society (low risk). Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results (1986), Australia [] parallel design II Adults, mild hypertensive (DBP: 90 – 100mmHg) Participants were then randomised to one of four groups: 1. Normal diet group Blood pressure (seated), cholesterol (did not report values for calculating change) 200 (n=100 in sodium and control groups) 12 weeks Low sodium 85.8 + 7.1 mmol/24hr Normal sodium 155.6 + 8.4mmol/24hr Mean changes between low sodium diet to normal sodium diet (from Graudal): trial:
Outcome assessors: unclear risk but did not give exact results) *Australian National Health and Medical Research Council Dietary Salt Management Committee Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results (1989), Australia [] parallel design study II Adults, with mild hypertension (DBP: 90 - 100mmHg) Participants were randomised to one of two groups: 1. low sodium intake group – diet containing less than 80mmol sodium/day plus placebo tablets 2. normal sodium intake group – diet containing less than 80mmol sodium/day plus NaCl tablets Blood pressure (seated after 5 min rest), plasma cholesterol 103 8 Low sodium intake: 90 (SEM: 6) mmol/24hr – change: -52 (SEM: 7), p<0.005 Normal sodium intake: 153 (SEM: 6) mmol/24hr – change: +19 (SEM: 7), p<0.05 p-value for change between groups: p<0.005 Mean difference between low sodium diet to normal sodium diet: SBP: -5.5mmHg (SEM: 1.46, CI: -2.64) DBP: -2.8mmHg (SEM: 0.84, CI: -1.15) States was no significant change in cholesterol, but does not give specific results trial
TONE et al. (2001), USA [] parallel design study II adults (60 – 80 years) taking 1 anti- hypertensive medication (SBP: <145mmHg, DBP: <85mmHg) (23% African American) Participants were randomised to one of two groups: 1.reduced sodium intake intervention (goal to achieve urinary sodium excretion of less than 80 mmol/L) 2. control (usual lifestyle) Anti-hypertensive medication was withdrawn for all participants 90 days (+ 14 days) after the start of the intervention. Resumption of anti-hypertensive medication, high BP (190/110mmHg) or a cardiovascular clinical event were treated as endpoints. Blood pressure (seated), events (as endpoint) 681 (BP data available for n=142 African American participants and n=471 African American participants) Median 29 months Differences in change in urinary sodium excretion between study groups: African-American participants: Women: -25 (95% CI: -47, (p=0.03) Men: -41 (95% CI: -13)mmol/24hr (p=0.007) participants: Women: -28 (95% CI: -41, (p<0.001) Men: -54 (95% CI: -42)mmol/24hr (p<0.001) Mean difference between reduced sodium and control groups: African-American participants: SBP: -4.9mmHg (SEM: 1.71, CI: -8.25, -1.55) DBP: -3mmHg (SEM: 1.2, CI: -5.35, -0.65) Non-African-American participants: SBP: -4.0mmHg (SEM: 1.01, CI: -5.98, -2.02) DBP: -1.6mmHg (SEM: 0.69, CI: -2.95, -0.25) Cardiovascular events: Stroke: Reduced sodium: 1 (individual and event), control: 2 (individual and event), p>0.99 :
Institutes of Health (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Compliance to sodium target (urinary data) Results Arroll et al. (1995), New Zealand [] parallel design study II Adults (aged 20 – 69 years), with hypertension (SBP> 115mmHg or DBP > 70mmHg Participants randomised to one of four groups: 1. Exercise (walking briskly for 40 mins 3 times/week) 2. Salt reduced diet 3. Exercise (walking briskly for 40 mins 3 times/week) plus salt reduced diet 4. Control Blood pressure (method not stated) 87 (n=181 in total study) 6 Without exercise: Low sodium diet: 107mmol/24hr Normal sodium diet: 120 mmol/24hr Without exercise: SBP: Control pre-diet: 145.3mmHg Control post-diet: (p>0.2) Sodium restriction 145.4mmHg Sodium restriction 136.3mmHg (p>0.2) DBP: month
As decision was made by EWG to exclude studies with exercise interventions, only groups 2 and 4 were included in analysis Control pre-diet: 94.0mmHg Control post-diet: 89.2mmHg (p>0.2) Sodium restriction 86.4mmHg Sodium restriction (p>0.2) Please note SEM for each value not reported, only range of SEM for all SBP and DBP measures Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Arroll et al. (1995) Unclear risk (no description of method of sequence generation) Unclear risk (no description of method of concealment of allocation) Participants: unclear risk Providers: high risk 13% (did not state from which group)- unclear risk No (high risk) No (low risk) Yes (low risk) National Foundation of New Zealand (low risk)
Outcome assessors: low risk Summary table Citation & location Study design NHMRC level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Benetos et al. (1992), France [] study II Adults (22 – 55 years) with hypertension (>90 - <115mmHg DBP) Participants were randomised to one of two groups: 1. Moderately restricted sodium diet plus 3.5g NaCl/day sodium) in capsules diet) 2. Moderately restricted sodium diet Resting pressure (supine) 20 4 weeks Normal sodium period: 163 + 13.3 mmol/24hr Low sodium period: 85 + 9.6 mmol/24hr (p<0.001) Mean changes between low sodium diet to normal sodium diet: SBP: (SEM: 1.88, CI: -2.82) DBP: -3.7mmHg (SEM: 1.28, CI: -1.19)
plus lactose capsules (low-sodium diet) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Benetos et al. (1992) Unclear risk (no description of method of sequence generation) Unclear risk (no description of method of concealment of allocation) Participants: low risk Providers: low risk Outcome assessors: unclear risk <10% ( low risk) No (unclear risk) No (low risk) Yes (low risk) Dassault Electronics (low risk) Summary table Citation & location design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results
et al. (1997), UK [] study II Older adults (60 – 78 years), both and hypertensive (SBP range: 123 – 205mmHg, DBP range: 64 – 112mmHg) All participants were prescribed a reduced sodium diet (80mmol/day) for 2 weeks. Following this period, they were then allocated to a cross-over arm: 1. 12 sodium tablets/day (total of 120mmol/day) 2. 12 placebo tablets/day pressure (supine), total cholesterol 47 (18 NT, 29 HT) 4 weeks Normotensive pts.: Normal sodium period: 167 + 54 mmol/24hr Low sodium period: 91 + 54 mmol/24hr (p<0.001) Hypertensive pts.: Normal sodium period: 182 + 46 mmol/24hr Low sodium period: 95 + 48 mmol/24hr (p<0.001) Mean changes between low sodium diet to normal sodium diet: Normotensive pts. SBP: -8.1mmHg (SEM: 2.77, CI: -13.53, -2.67) DBP: -3.9mmHg (SEM: 1.54, CI: -6.92, -0.88) Hypertensive pts. SBP: -6.6 mmHg (SEM:2.51, CI: -11.52, DBP: -2.8mmHg (SEM: 1.33, CI: -5.41, -0.19) Mean total cholesterol was 5.9+ 1.1 mg/dL during normal sodium period and 6.0 + 1.0 mg/dL during low salt period (NS, p-value not given, not given separately for HT and NT pts.) over
Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Cappuccio et al. (1997) Low risk numbers handled by author not involved in the clinical assessment) Low risk (handled by author not involved in clinical assessment) Participants: low risk Providers: low risk Outcome assessors: unclear risk 2% (one participant) – low risk No (unclear risk) No (low risk) Yes (low risk) International Foundation for the Promotion of Nutrition Research and Nutrition Education (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Carney et al. (1991), Australia study II Adults (30 – 65 years), with treated All participants were randomly allocated to a cross-over arm: Blood pressure (supine for 10 min, erect for 5 min) Note change in standing BP 11 6 weeks Sodium tablets: 272 + 24 mmol/24hr Placebo tablets: 170 + 24 Mean changes between low sodium diet to normal sodium diet: generated over
[] with medication 1. 100mmol tablets/day 2. Placebo tablets The study did not prescribe a diet, and assumed that participants continued their usual diet throughout not able to be calculated as insufficient data in paper mmol/24hr (p<0.001) Supine: SBP: -1mmHg (SEM: 3.49, CI: 5.84) DBP: (SEM: 2.96, CI: -4.80, 6.80) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Carney et al. (1991) Unclear risk (no description of method of sequence generation) Unclear risk (no description of method of concealment of allocation) Participants: low risk Providers: low risk Outcome assessors: unclear risk 0% (low risk) Not required (low risk) No (low risk) Unclear risk (Insufficient data on standing BP to calculate) Not stated (unclear risk) (company supplied capsules but no indication of funding)
Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Cobiac et al. (1992), Australia [] parallel design study II Older adults aged 60 – 80 years, and mildly hypertensive (DBP: < 105mmHg) (mean During the 2 week run-in phase, all participants were encouraged to reduce sodium intake to less than 70mmol/day. Participants were also provided with NaCl tablets providing 80mmol sodium/day and 8g sunflower oil capsules during this time. Participants were then randomised to one of four groups: 1. sunflower oil (5g) with normal sodium (with tablets providing 80mmol sodium/day) Blood pressure (seated after at least 5 min rest) 106 (54 in sunflower oil groups, 52 in fish oil groups) 4 weeks Sunflower oil groups: Normal sodium period: 152 + 10 mmol/24hr Low sodium period: 79 + 7 mmol/24hr (p<0.001 compared to run-in phase) Fish oil groups: Normal sodium period: 145 + 8 mmol/24hr Low sodium period: 70 + Mean changes between low sodium diet to normal sodium diet: Sunflower oil groups: SBP: -2.7mmHg (SEM: 4.99, CI: 7.08) DBP: 0.6mmHg (SEM: 3.92, CI: 8.28) Fish oil groups: SBP: -3.1mmHg (SEM: 5.86, CI: 8.39)
study (1989b) the low sodium arm were allocated to one of two cross-over arms: 1. 80mmol sodium tablets/day with restricted sodium diet continued 2. placebo with restricted sodium diet continued P<0.05 (between groups) Crossover study design: Normal sodium period: 198.8 + 37.4 mmol/24hr Low sodium period: 122.6 + SBP: -13.0mmHg (CI: -25.92, -0.08) DBP: -1.80mmHg (CI: -8.62, 5.02) Crossover design study: SBP: -9.70mmHg (CI: -25.78, 6.38) (from WHO) DBP: Change data not provided in WHO, see spreadsheet for means Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Dodson et al. (1989) Both study designs: Both study designs: Parallel design study Parallel design study: Parallel design study: No (low risk) Yes (low risk) Not stated (unclear risk) (company
Low risk (computerised random number program) Unclear risk (no description of method of concealment of allocation) Participants: unclear risk Providers: high risk Outcome assessors: low risk Crossover study Participants: low risk Providers: low risk Outcome assessors: low risk <5% (low risk) Crossover design >20% (high risk) No (unclear risk) Crossover design No (high risk) supplied capsules but no indication of funding) Summary Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Dubbert et al. (1995), USA [] parallel design study II Older adults (aged 60 – 80 years), with essential hypertension Participants were randomised to one of three groups: 1. Dietary sodium goal of 87mmol/day Blood pressure (seated) 122 3 months Mean change in urinary sodium levels by group: DI/FB: Caucasian participants: (sig greater Mean difference between low sodium diet to normal sodium diet:
Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Dubbert et al. (1995) Low risk (random number table) Unclear risk (randomisation procedure stratified by race) Participants: unclear risk Providers: high risk Outcome assessors: unclear risk >20% (high risk) No (high risk) No (low risk) Unclear risk (Limited detail available on significance level of changes in urinary sodium levels) Department of Veteran’s Affairs (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results et al. (1984), [] parallel design study II Adults with mild hypertension (DBP: 95 – 110mmHg) Participants allocated to either: 1. Normal diet 2. Sodium restricted diet – Blood pressure (after 10 mins supine rest and after 2 mins standing), cholesterol and HDL 94 24 weeks (placebo duration 12 weeks) During placebo period: Normal sodium period: 130 + Mean difference between low sodium diet to normal sodium diet (from Graudal, not clear if this is placebo period only):
limited to 70mmol/day All participants received in random order chlorthalidone, metoprolol, a fixed combination of these drugs for 4 weeks each, alternated with 4 weeks of placebo 50 mmol/24hr Low sodium period: 72 + 31 mmol/24hr (p<0.05) SBP: (SEM: 4.01, CI: 5.16) DBP: -2.5mmHg (SEM: 2.46, CI: -7.32, 2.32) From the article: mean difference in BP during placebo period: SBP: -2.7 +2.2 (p=0.12) (supine), -4.4 + 2.3 (p=0.025) (standing) DBP: -3.4 +1.7 (p=0.025) (supine), -1.0 + 1.6 (p=0.25) (standing) States there was no significant change in cholesterol and HDL, but does not give specific results for normal and low sodium diets Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of Ceasing study early for benefit Reporting all outcome results Funding source
where required Erwteman et al. (1984) Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: high risk Providers: high risk Outcome assessors: low risk 12% (however unclear from which study group) (unclear risk) No (high risk) No (low risk) Unclear risk (Reported that there was no significant change in cholesterol, HDL and glucose but did not report specific results) Funding source not stated (unclear risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results et al. (1984), Sweden [] parallel design study II Obese adult males with hypertension (DBP: 94 – 115mmHg) Following a 3 – 4 week basal period, participants were randomly allocated to one of two groups: 1. Energy restricted diet (aimed at weight reduction of 1kg /week) with Auscultatory blood pressure (after 60 mins supine rest), resting blood pressure 30 12 weeks (sodium restriction period: 9 weeks) Energy restricted, normal sodium diet: 194.6 (SEM: 13.4) mmol/24hr Energy restricted, low sodium diet: 95.5 (SEM: 7.7) mmol/24hr (significantly Mean difference between low sodium diet to normal sodium diet (not stated whether this is auscultatory or
Fagerberg et al. (1984) Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: high risk Providers: high risk Outcome assessors: unclear risk 12% (however unclear from which study group) – unclear risk No (high risk) No (low risk) Yes (low risk) Swedish National Association Against Heart and Chest Diseases, Swedish Medical Research Council, Goteborg Medical Society (low risk) Summary Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Fotherby et al. (1993) and Fotherby et al. (1997), UK [, ] study II Older adults (aged 66 – 79 years) with essential hypertension (SBP: > 160mmHg, DBP: > 95 mmHg) All participants were prescribed a reduced sodium diet for 4 Following this period, they were then randomly allocated to a cross-over arm: Blood pressure (supine after 5 min rest and after 1 min standing) (reported in Fotherby et al., 1993). Total cholesterol, HDL and LDL (reported in Fotherby et al., 1997) 17 5 Normal sodium period: 174 + 40 mmol/24hr Low sodium period: 95 + 36 mmol/24hr (p<0.01) Mean difference between low sodium diet to normal sodium diet: Supine: SBP: -8mmHg (SEM: 3.5, CI: -1.14) over trial.
1. 8 slow sodium tablets/day (total of 80mmol/day) 2. 8 placebo tablets/day DBP: 1.0 mmHg (SEM:2, CI: -2.92, 4.92) Cholesterol: (CI: 15.63) HDL: -7.70mg/dL (CI: -20.03, 4.63) LDL: 0.0mg/dL (CI: -20.77, 20.77) data from Graudal, does not appear to be based on change Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source
Fotherby et al. (1993) and Fotherby et al. (1997) Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk One participant (5.6%) lost to follow-up (low risk) No (unclear risk) No (low risk) Yes (low risk) British Heart Foundation (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Gates et al. (2004), USA [] study II Adults (aged 50 years) with stage 1 systolic hypertension Participants randomly allocated to start on one of two cross-over arms: 1. Reduced sodium diet plus salt tablets (intended to return participants to Blood pressure (seated and supine), 24hr ambulatory BP, total cholesterol, HDL, LDL 12 4 weeks Normal sodium period: ~ 160 – 170mmol/24hr (estimated from figure, exact values not given) Low sodium period: ~60 – 70mmol/24hr (estimated from Mean difference between low sodium diet to normal sodium diet: Supine: SBP: -3mmHg (SEM: 1.84, CI: -6.61, -0.61) DBP: -1.2mmHg (SEM: 1.46, CI: -4.06, 1.66) over trial
usual sodium intakes) 2. Reduced sodium diet plus placebo figure, exact values not given) (p<0.05) Cholesterol: 5.00mg/dL (CI: -38.21, 48.21) HDL: -1.90mg/dL (CI: 25.64) LDL: 8.10mg/dL (CI: 46.12) Lipid data from Graudal, does not appear to be based on change Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source
Gates et al. (2004) Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk No loss to follow up (low risk) Not required (low risk) No (low risk) Yes (low risk) National Institute of NCRR General Clinical Research Centre, American Heart Association (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Gillies et al. (1984), Australia [] study II Adults with moderate hypertension, some receiving medication (information on number of participants on Participants randomly allocated to on one of two cross-over arms: 1. Dietary advice for moderate dietary salt restriction Blood pressure (supine and standing), MAP Note: specific values for MAP not given in study, stated as having no 24 6 Salt restriction resulted in decrease from 169mmol/24hr (SEM: 13) to 92mmol/24hr (SEM: 7) – unclear if this change was from baseline or Mean difference between low sodium diet to normal sodium diet: Supine: SBP: -2.4mmHg (SEM: 2.51, CI: -7.32, 2.52) over
medication not given) 2. normal diet significant changes. compared to normal sodium diet (p>0.001) DBP: -2.6mmHg (SEM: 2.21, CI: -6.93, 1.73) Note data also given for patients on and not on diuretics, however insufficient information given to calculate Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Gillies et al. (1984), Australia Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: unclear risk Providers: high risk Outcome assessors: unclear risk 14.2% loss to follow up (unclear from which group) (unclear risk) No (high risk) No (low risk) Unclear risk (Insufficient data on MAP to calculate change in BP) Not stated (unclear risk) Summary table
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Grobbee et al. (1987), [] study II adults (18 – 28 years) with mild hypertension (SBP > 140mmHg, DBP> 90mmHg) Participants randomly allocated to start on one of three cross-over arms: 1. Low sodium diet plus sodium supplementation (90mmol/day) 2. Low sodium diet plus potassium supplementation (72mmol/day) 3. Low sodium diet plus placebo Blood pressure (supine), serum cholesterol 40 6 weeks Normal sodium period: 129 +5 mmHg Low sodium period: 57 + 5 mmHg Low sodium/high potassium: 69 + 6 mmHg (p<0.005) Mean difference between low sodium diet to normal sodium diet (assuming that the potassium group was excluded by Graudal, although this is not clearly stated): SBP: -0.8mmHg (SEM: 1.51, CI: -3.76, 2.61) DBP: -0.8mmHg (SEM: 1.44, CI: -3.62, 2.02) Cholesterol: 0.0 mg/dL (CI: -15.31, 15.31) data from Graudal, does not appear to be based on change Key features for bias assessment of randomised trials over
Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Grobbee et al. (1987) Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk <5% loss to follow-up (low risk) No (unclear risk) No (low risk) Yes (low risk) Netherlands Heart Foundation (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results
He et al. (2009), UK [] study II Caucasian, African and Caribbean and Asian adults (30 – 75 years), with mild hypertension (SBP: 140 – 170mmHg, DBP: 90 – 105mmHg) Following consuming a reduced salt diet (with a goal of 85mmol/day) for 2 weeks, participants were randomly allocated to start one of the two cross-over arms: 1. Reduced salt diet with sodium supplementation (90mmol/day) 2. Reduced salt diet with placebo Blood pressure (sitting after 5 – 10 min rest), 24hr ambulatory BP 169 (n=71 Caucasian, n=29 Asian, n=69 African and 6 weeks All participants: Normal sodium period: 165 +58 mmHg Low sodium period: 110 + 49 mmHg (p<0.001) Caucasian pts. Normal sodium period: 163 +54 mmHg Low sodium period: 104 + 54 mmHg (p<0.001) Asian pts. Normal sodium period: 176 + 64 mmHg Low sodium period: 108 + 49 mmHg (p<0.001) Mean difference between low sodium diet to normal sodium diet: Seated: Caucasian pts. SBP: -4.8mmHg (SEM: 1.24, CI: -7.23, -2.37) DBP: -2.2mmHg (SEM: 0.66, CI: -3.49, -0.91) Asian pts. SBP: -5.40mmHg (SEM: 1.93, CI: -9.18, -1.62) DBP: -2.2mmHg (SEM: 1.04, CI: -4.24, -0.16) African and Caribbean pts. )
African and Caribbean pts. Normal sodium period: 162 +59 mmHg Low sodium period: 116 + 44 mmHg (p<0.001) SBP: -4.80mmHg (SEM: 1.24, CI: -7.23, -2.37) DBP: (SEM: 0.67, CI: -3.51, -0.89) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source He et al. (2009) Low risk (computer random number) Low risk (computer generated random number, conducted by individuals not involved in the conduct of the study) Participants: low risk Providers: low risk Outcome assessors: low risk <10% loss to follow-up (low risk) No (unclear risk) No (low risk) Yes (low risk) UK Food Standards Agency (low risk)
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Howe et al. (1994), Australia [] parallel design study II Adults (aged 34 – 82 years) with hypertension treated with ACE inhibitors Participants were instructed to reduce dietary sodium to 70mmol/day during a 4 week run-in phase (also included 80mmol/day NaCl tablets, providing a total sodium intake of 150mmol/day). Participants were then randomly assigned to one of four intervention groups: 1. low sodium diet (70mmol/day) with placebo and fish oil (5g/day) 2. low sodium diet (70mmol/day) plus NaCl tablets (total sodium intake:150mmol/day) with fish oil Blood pressure (seated after at least 5 min rest), total cholesterol (however did not report changes in cholesterol) 56 (n=28 in oil groups, n=28 in fish oil groups) 6 weeks oil groups: Normal sodium period: 155 mmol/24hr Low sodium period: 75mmol/24hr Fish oil groups: Normal sodium period: 160mmol/24hr Low sodium period: 85mmol/24hr (note values are estimated from figure) For oil groups combined: Mean changes between low sodium diet to normal sodium diet: Olive oil groups: SBP: (CI: 7.55) DBP: -2mmHg (CI: 3.54) Fish oil groups: SBP: -4.0mmHg (CI: 10.13) DBP: -1.0mmHg (CI: -7.50, 5.50)
3. low sodium diet (70mmol/day) plus placebo and olive oil 4. low sodium diet (70mmol/day) plus NaCl tablets (total sodium intake:150mmol/day) with olive oil Normal sodium period: 158mmol/24hr Low sodium period: 78mmol/24hr Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Howe et al. (1994) Unclear risk (no description of method of sequence generation) Unclear risk (no description of method of concealment of allocation) Participants: low risk Providers: low risk Outcome assessors: low risk 8.2% (but unclear from which group) – unclear risk No (unclear risk) No (low risk) Unclear risk (Cholesterol reported as not changing but exact results not provided) Bristol Myers Squibb (pharmaceutical company) – unclear risk Summary table
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Research Group (1990), USA [] parallel design study II Adults (aged 25 – 49 years) with diastolic blood pressure of 76 – 90mmHg Participants randomly assigned to one of five groups: 1. control (no dietary counselling) - 2. reduced calories (participants with high BMI only) 3. reduced sodium (goal of urinary sodium excretion < 70mmol/day) 4. reduced sodium and calories (participants with high BMI only) (goal of urinary sodium excretion < 70mmol/day) 5. reduced sodium and increased potassium (goal of urinary sodium excretion < 70mmol/day, urinary pressure (sitting after 5 min rest), mortality also noted. 351 (in groups 1 and 3, n= 841 in whole study) 3 years Difference in change in urinary sodium between reduced sodium and control groups (sodium – control): -4.2 (SEM: 2.1) mmol/8 hr Mean difference between reduced sodium and control groups: SBP: (SEM: 0.99, CI: -1.84, 2.04) DBP: 0.2mmHg (SEM: 0.71, CI: 1.59) Mortality reported as one death each in control and reduced sodium groups (no statistical analysis reported)
potassium excretion > 100mmol/day) Note: only groups 1 and 3 used in analysis to confounding effect of calories and potassium Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing early for benefit Reporting all outcome results Funding source Hypertension Prevention Research Group (1990) Unclear risk (method of randomisation not described) Unclear risk (method of allocation concealment not described) Participants: unclear risk Providers: high risk Outcome assessors: low risk 10% loss to follow-up (for groups 1 and 3) (low risk) No (unclear risk) No (low risk) Yes (low risk) National Heart, Lung and Blood Institute (low risk) Summary
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Jablonski et al. (2013), UK [] study II Adults (50 – 79 years), with high-normal or Stage 1 systolic hypertension (SBP: 130 – 159mmHg, DBP: <99mmHg) All participants were instructed to reduce dietary sodium intake to ~50mmol/day. Participants were randomised to start one of two study arms: 1. Reduced salt diet with 100mmol sodium/day from NaCl tablets 2. Reduced salt diet with placebo Blood pressure (supine), total cholesterol, LDL, HDL. Note: vascular endothelial function appears to be the primary outcome 17 5 Normal sodium diet: 153 + 27 mmol/day Low sodium diet: 70 + 30 mmHg (p<0.001) SBP: Baseline: 138 + 7 mmHg Low sodium: 128 + 10mmHg (p<0.01) Normal sodium: 140 + 15mmHg DBP: Baseline: 83 + 7 mmHg Low sodium: 79 + 6mmHg Normal sodium: 82 + 6mmHg Total cholesterol: Baseline: 196 + 27 mg/dL Low sodium: 187 + 27mg/dL Normal sodium: 194 + 22 mg/dL
Jablonski et al. (2013) Unclear risk (no description of method of sequence generation) Unclear risk (method of allocation concealment not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk 15% loss to follow-up (prior to completing vascular measurements) – unclear risk Unclear risk No (low risk) Yes (low risk) National Institutes of Health (low risk) Summary Citation & location design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results et al. (1975), USA [] study II Adult males (24 - 47 years), with normotensive BP (below 150/90mmHg) Participants were randomised to start one of three study arms: 1. Liquid dietary supplement containing sodium/day Blood pressure (supine, standing), total cholesterol. Only mean BP (calculated as diastolic plus 40% pulse 8 4 High sodium diet: 307 + 56 mEq/24hr Intermediate sodium diet: 159 + 31 mmol/day Mean BP supine Low sodium: 90 + Intermediate sodium: 88 + 7 mmHg High sodium: 90 + 5 mmHg Total cholesterol:
2. Liquid dietary supplement containing 210mEq sodium/day 3. Liquid dietary supplement containing 410mEq sodium/day pressure) reported Low sodium diet: 10 + 10 mmHg (p<0.05) Low sodium: 200 + 26 mg%/100mL Intermediate sodium: 200 + 25 mg%/100mL High sodium: 211 + 29 mg%/100mL Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing early for benefit Reporting all outcome results Funding source Kirkendall et al. (1975) Low risk (modified square design) Unclear risk (method of allocation concealment not described) Participants: low risk Providers: unclear risk Outcome assessors: low risk No loss to follow up (low risk) Not required (low risk) No (low risk) Reported no significant change in BP, but only reported mean BP values National Institutes of Health (low risk)
Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results et al. (1982), UK [] study II Adults (aged with mild to moderate hypertension (SBP: 135 – 185mmHg, DBP: 90 – 110mmHg) Following dietary instructions to consume a reduced salt diet (with a goal of 60 - 80mmol/day) for 2 weeks, participants were randomly allocated to start one of the two cross-over arms: 1. Reduced salt diet with “slow” sodium supplementation (designed to restore sodium intake to match pt.’s baseline urinary sodium excretion) 2. Reduced salt diet with placebo pressure (supine and standing), mean arterial pressure Insufficient data in to calculate MAP 19 4 weeks Normal sodium diet: 160 mmHg (estimated from figure, exact values not given) Low sodium diet: 83 + 11 mmHg (p<0.001) Mean difference between low sodium diet to normal sodium diet: Seated: SBP: -10mmHg (SEM: 2.76, CI: -15.41, -4.59) DBP: -5mmHg (SEM: 1.76, CI: -8.45, -1.55) Key features for bias assessment of randomised trials
Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source MacGregor et al. (1982) Unclear risk (no description of method of sequence generation) Unclear risk (not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk 0% loss to follow-up (low risk) Not required (low risk) No (low risk) Unclear risk (Insufficient data in paper to calculate changes in MAP for group) Welcome (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results
(total 50mmol sodium/day) 2. Restricted sodium diet plus 70mmol NaCl tablets/day and placebos (total 100mmol sodium/day) 3. Restricted sodium diet plus 160mmol NaCl tablets/day (total 200mmol sodium/day) Note: Groups 1 and 3 used for analysis by Graudal (insufficient data in paper to allow manual extraction for excel sheet) Changes in standing BP also not able to be calculated due to insufficient data on baseline levels in paper 50mmol sodium/day arm: 49 (SEM: 8, CI: 34, 65) mmHg (p<0.001) Note: Groups 2 and 3 used for analysis Intermediate: 155mmHg (SEM: 3) DBP: Low: 91mmHg (SEM: 2) Intermediate: 95mmHg (SEM: 2) In follow-up 1 year after study completed, SBP was: 142mmHg (SEM: 3), DBP was: 87mmHg (SEM: 2). 24hr urinary sodium excretion was 54mmol/24hr (SEM: 7) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of Ceasing early for benefit Reporting all Funding source
where required outcome results MacGregor et al. (1989) Unclear risk (no description of method of sequence generation) Unclear risk (method of concealment of allocation not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk 0% loss to follow-up (low risk) Not required (low risk) No (low risk) High risk (Mean arterial pressure measured but results not reported) Not stated (company supplied capsules but no indication of funding) – unclear risk Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Mascioli et al. (1991), USA [] study II Adults (aged normotensive (SBP: <150mmHg, DBP: 80 – 89mmHg) Following dietary instructions to consume a reduced salt diet for 8 weeks, participants were randomly allocated to start Blood pressure (seated) 48 4 weeks Pooled values not given for urinary sodium levels in both diets. Difference between the normal sodium and low sodium periods Mean difference between low sodium diet to normal sodium diet: SBP:
Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Maxwell et al. (1984), USA [] parallel design study II Obese adults, with hypertension (DBP: > 90mmHg) Participants were randomised to consume one of two dietary supplements as meal replacements: 1.320 calories/day as 30g of CHO and 45g of protein, plus 600mg calcium, 350mg phosphorus, 150mg magnesium, 100% daily allowance of iron, copper, zinc, and all vitamins. Total potassium intake was 60mEq/day, sodium was 40mEq/day 2. Same dietary supplement with same potassium intake, however sodium was Blood pressure (seated) 30 12 weeks Low sodium supplement: 39 + 4mEq/24hr Normal sodium supplement: 200 + 30mEq/24hr Note results are from week 8 of 12 week study, results from week 12 not given Mean difference between low sodium supplement and normal sodium supplement: SBP: (SEM: 6.72, CI: -15.17, 11.17) DBP: 2mmHg (SEM: 3.84, CI: -5.53, 9.53)
210mEq/day (via NaCl tablets) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Maxwell et al. (1984) Unclear risk (method of randomisation not stated) Unclear risk (method of randomisation not stated) Participants: unclear risk Providers: unclear risk Outcome assessors: unclear risk 0% loss to follow-up (low risk) Not required (low risk) No (low risk) Unclear risk (Urinary sodium data only reported for week 8 in paper) University Medical Research Foundation (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question size Intervention duration Compliance to sodium target (urinary data) Results
et al. (1997), USA [] study II Adults (mean age 51.6 years) with mild to moderate essential hypertension (DBP: 95 – 115mmHg) For 4 weeks prior to the study starting, participants consumed an ad libitum NaCl diet Following this, over a 4 week period, all participants then received the required amount of isradipine (2.5mg or 5mg/day) to maintain their DBP at <90mmHg. Participants were instructed to consume a low sodium diet (60 – 80mmol/24hr), and were randomised to start one of two study arms: 1. Restricted sodium diet plus supplementary NaCl (100mmol/24hr) 2. 1. Restricted sodium diet plus placebo Blood pressure (seated after 15 min rest), total cholesterol, LDL, HDL 99 4 weeks Low sodium period: 120.5 + 68.9mmol/24hr Normal sodium period: 175.9 + 68.7 mmol/24hr (p<0.0001) Mean difference between low sodium period and normal sodium period: SBP: -4.90mmHg (SEM: 1.23, CI: -7.31, -2.49) DBP: (SEM: 0.81, CI: -4.49, -1.31) Total cholesterol: 8.20 mg/dL (CI: -2.89, 19.29) HDL: 0.10 mg/dL 3.99) LDL: 5.90 mg/dL (CI: 16.16) Lipid data from Graudal, does not appear to be based on change Key features for bias assessment of randomised trials 3.79,
Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing early for benefit Reporting all outcome results Funding source McCarron et al. (1997) Low risk (computer generated sequence) Unclear risk (method of concealment of randomisation not described) Participants: low risk Providers: low risk Outcome assessors: low risk 2% loss to follow-up (low risk) Yes (low risk) No (low risk) Unclear risk (Reported that creatinine, albumin, haemocrit and haemoglobin were unchanged but did not report specific results) Sandoz Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results
Meland et al. (1997), Norway [] study II Adults (aged mean age:50) with mild to moderate hypertension (mean SBP: 146mmHg, mean DBP: 95mmHg) Participants were randomly allocated to start one of the two cross-over arms: 1. Moderately reduced salt diet with salt supplementation (providing 50mmol sodium/day) 2. Moderately reduced salt diet with placebo Blood pressure (seated after 3 min rest), total cholesterol, HDL 16 8 weeks Low sodium period: 125 (95% CI: 104 – 146) mmol/24hr Normal sodium period: 191 (95% CI: 159 – 223) mmol/24hr (not stated if significantly different) Mean difference between low sodium period and normal sodium period: SBP: -4mmHg (SEM: 2.47, CI: -8.84, 0.84) DBP: -3mmHg (SEM: 1.36, CI: -5.67, -0.33) cholesterol: 0.0 mg/dL (CI: -27.32, 27.32) HDL: -3.80 mg/dL 6.87) Lipid data from Graudal, however does not appear to be based on change Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source
Meland et al. (1997) Unclear risk (method of randomisation not stated) Unclear risk (method of concealment of randomisation not described) Participants: low risk Providers: low risk Outcome assessors: unclear risk 0% loss to follow-up (low risk) Not required (low risk) No (low risk) Yes (low risk) Research Council of Norway (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Meland et al. (2009), Norway [] parallel design study II Adults (aged with hypertension (SBP: >160mmHg, DBP: >90mmHg) (on drug treatment) All participants received dietary advice to consume a moderate diet, then randomised into one of two groups: 1. Moderately reduced salt diet Blood pressure (seated after 2 min rest), total cholesterol, HDL 46 8 weeks Low sodium period: 83 mmol/24hr Normal sodium period: 126 mmol/24hr (p=0.11) Note values calculated from Mean difference between low sodium period and normal sodium period: SBP: -5mmHg (SEM: CI: -12.43, 2.43) DBP: -5mmHg (SEM: 1.38, CI: -7.70, -2.30)
Citation & location design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Melander et al. (2007), Sweden [] study II Adults (mean age 53±11 years), without known hypertension (mean SBP: 139mmHg, mean DBP: 86.3mmHg) All participants received all meals and drinks throughout the study duration to provide a total daily intake of 50mmol of sodium/salt (NaCl). Participants were randomly allocated to start one of the two cross-over arms: 1. Provided food and drinks plus 100mmol NaCl/day 2. Provided food and drinks plus placebo pressure (supine after 30 min rest), 24hr ambulatory BP 39 4 weeks Low sodium period: 50.7 + 17.3 mmol/24hr Normal sodium period: 140 + 39.5 mmol/24hr (p<0.0001) Mean difference between low sodium period and normal sodium period: Supine: SBP: -6mmHg (SEM: 1.18, CI: -8.31, -3.69) DBP: -2.3mmHg (SEM: 0.86, CI: -3.99, -0.61) Key features for bias assessment of randomised trials
(DBP: 95 – 109mmHg) 2. Dietary advice to reduce sodium intake to 70 – 100mmol/day 3. chlorothiazide (500 mg twice daily) 4. propranolol (up to 480 mg/day) and a diuretic Note: only groups 1 and 2 used in this analysis however insufficient data reported in paper to analyse Control group 180 (SEM: 9) mmol/24hr (p<0.05) SBP: -1.5mmHg (SEM: 5.55, CI: -12.38, -9.38) DBP: -7mmHg (SEM: 2.77, CI: -12.43, -1.57) Mortality: 1 participant in the restricted sodium died due to MI (compared to 0 participants in control, statistical analysis not conducted) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source
Morgan et al. (1978) Unclear risk (method of randomisation not stated) Unclear risk (method of allocation concealment not stated) Participants: low risk Providers: high risk Outcome assessors: low risk 7.5% (low risk) No (unclear risk) No (low risk) Unclear risk (Reported that biochemical values were similar at the end of the study but did not report values.) Department of Veterans Affairs and National Heart Foundation of Australia (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Morgan et al. (1981), Australia [] parallel design study II Adult (aged 28 – 50 years), with hypertension (DBP: >90 - <105mmHg Participants randomly divided into four groups: 1. Control group (no treatment) 2. Advised to reduce dietary sodium to 70mmol/day Blood pressure (supine after 10 mins, standing after 5 mins) Note: data on standing BP not in sufficient detail to calculate 12 (in sodium and control arms only) (6 males, 6 females) Due to the way data was presented, it had to be 8 Males Restricted sodium 78 + 8 mmol/24hr (p<0.001 compared to start) Males DBP: Control pre-diet: 96mmHg (SD not stated to be ‘less than + 7’) Control post-diet: 94mmHg
Note study also included a group of pts. with DBP >105mmHg, control group was treated with chlorothiazide. As it is not possible to isolate the effect of sodium in these participants, they were not included in this analysis (results given separately in the paper). divided by gender Control group: 170 + 15 mmol/24hr Females Restricted sodium group: 58 + 7 mmol/24hr (p<0.001 compared to start) Control 125 + 10 mmol/24hr Sodium restriction pre-diet: 97mmHg Sodium restriction post-diet: 87mmHg (p<0.01 compared to start value, p<0.05 compared to control) Females DBP: Control pre-diet: 94mmHg (SD not given, all SD’s stated to be ‘less than + 7’) Control post-diet: 92mmHg Sodium restriction pre-diet: 95mmHg Sodium restriction post-diet: 89mmHg (p<0.01 compared to start value) Key features for bias assessment of randomised trials
Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Morgan et al. (1981) Unclear risk (method of randomisation not stated) Unclear risk (method of allocation concealment not stated) Participants: unclear risk Providers: high risk Outcome assessors: low risk None reported (low risk) Not required (low risk) No (low risk) Unclear risk (Did not report changes in SBP in sufficient detail to be able to calculate for each (same for standing SBP and DBP)) Department of Veterans Affairs and National Health and Medical Research Council (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Morgan et al. (1987), Australia [] parallel design study II males (aged 50 – 65 years), with hypertension treated with Participants randomly divided into two groups: 1. normal diet pressure (supine, standing) Note: results not provided 20 6 months Restricted sodium group: 75 + 7 mmol/24hr SBP: Control initial (prior to medication cessation: 143 + 5mmHg Trial
Sodium restriction pre-diet: 83 + 2 mmHg Sodium restriction post drug cessation (week 1): 86 + 3 mmHg Sodium restriction post-diet: 90 + 2mmHg (p<0.05 compared to change in control) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Morgan et al. (1987) Unclear risk (method of randomisation not stated) Unclear risk (method of allocation concealment not stated) Participants: unclear risk Providers: high risk Outcome assessors: low risk None reported (low risk) Not required (low risk) No (low risk) Unclear risk (Change in standing BP not reported) Department of Veterans Affairs and National Health and Medical Research Council (low risk) Summary table
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Nestel et al. (1993), Australia [] parallel design study II Older adults aged 60 – 79 years, (mean SBP: DBP: 72.5mmHg) Participants were all advised to reduce dietary sodium intake and consume a diet low in fat, and linoleic acid. Dietary sodium targets were 80mmol/day men, 70mmol/day women. Low sodium foods were provided Participants were then randomised into one of 4 groups: Group 1: low sodium, with 1g acid Group 2: added sodium (participants consumed 80mmol/day sodium Blood pressure (seated after at least 5 min rest) 66 (n=30 females, n= 36 Breakdown not shown for different oils 6 weeks Females: Normal sodium period: 150 + 45 mmol/24hr Low sodium period: 77 + 33 mmol/24hr Males: Normal sodium period: 162 + 49 mmol/24hr Low sodium period: 106 + 49 mmol/24hr Females: SBP: Normal sodium period (pre): 118 + 14mmHg Normal sodium period (post): 125 + 17mmHg Low sodium period (pre): 121 + 12mmHg Low sodium period (post): 118 + 9mmHg DBP: Normal sodium period (pre): 68 + 9mmHg Normal sodium period (post): 72 + Low sodium period (pre): 68 + 9mmHg
Nowson et al. (2003), Australia [] study II Adults (aged 33 – 74 years), both normotensive (n=92) (mean SBP: 121.9mmHg, mean DBP: 78.1mmHg) and hypertensive (n=16)(mean SBP: 151.7mmHg, mean DBP: 151.7mmHg, 85.7mmHg) Participants received dietary advice to reduce dietary sodium (to 50mmol/day) and to increase potassium intake (to a target of 80mmol/day). Participants were then randomly allocated to start one of the two cross-over arms: 1. reduced sodium diet plus 120mmol sodium supplements /day 2. reduced sodium diet plus placebo Blood pressure (clinic - seated after a 5 min rest, home – after 10 min rest, and 24hr ambulatory BP) 92 pts. (data on change in outcomes not given for hypertensive pts.) 64weeks Low sodium period: 50.9 +4.1 mmol/24hr Normal sodium period: 138.7 + 4.0 mmol/24hr (p=0.001) Mean difference between low sodium period and normal sodium period (NT pts. only): Seated (office): SBP: 0.4mmHg (SEM: 0.8, CI: 1.97) DBP: 0.0mmHg (SEM: 0.6, CI: 1.18) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing early for benefit Reporting all outcome results Funding source 1.17,
Nowson et al. (2003) Low risk (random number generator used) Low risk (Examiners blinded to allocation, randomisation procedure stratified by household) Participants: low risk Providers: low risk Outcome assessors: low risk 15.6% loss to follow-up (and unclear from study period) – unclear risk No (high risk) No (low risk) High risk (data on changes in outcomes not reported for hypertensive pts.) National Health and Medical Research Committee and the Rebecca Cooper Foundation (low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Parker et al. (1990), Australia [] parallel design study II Adult males(aged 20 – 70 years), with stable, treated hypertension (SBP: DBP<115mmHg) Participants consumed a low sodium diet (60mmol/day) plus 100mmol NaCl tablets/day for a 2 week run-in period. They were then randomly assigned to one of four groups: pressure (supine and standing) 59 (normal alcohol: n= 28, low alcohol: n= 31) 4 weeks All participants: Low sodium diet: 68.6 + 8.0 mmol/24hr Normal sodium diet: 141.7 + 7.6 mmol/24hr Regular alcohol participants: Mean difference between low sodium period and normal sodium period: Supine: Regular alcohol participants:
1. low sodium diet plus 100mmol NaCl tablets/day and alcohol intake 2. low sodium diet plus placebo and usual alcohol intake 3. low sodium diet plus 100mmol NaCl tablets/day and low alcohol beer 4. low sodium diet plus placebo and low alcohol beer Low sodium diet: 70 mmol/24hr Normal sodium diet: 130 mmol/24hr (estimated from figure) Low alcohol participants: Low sodium diet: 60 mmol/24hr Normal sodium diet: 140 mmol/24hr (estimated from figure) SBP: -0.1mmHg (SEM: 2.72, CI: 5.23) DBP: 0.8mmHg (SEM: 1.57, CI: 3.88) Low alcohol participants: SBP: (SEM: 2.15, CI: -2.01, 6.41) DBP: 0.5mmHg (SEM: CI: 2.79) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source
(participants instructed to avoid all foods with added sodium and select low sodium bread) (only groups 1 and 2 used by Graudal in analysis) 3. regular diet + diuretics (100mg spironolactone + 100mg hydrochlorothiazide) 4. moderate sodium restriction + diuretics information on baseline data in paper (note data is for placebo periods only) SBP: -6.7mmHg (SEM: 9.75, CI: -25.81, 12.41) DBP: 3.2mmHg (SEM: 5.91, CI: -8.38, 14.78) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source
Parijs et al (1973) Unclear risk (Intervention decided by odd or even number; manner in which numbers were generated and given to participants not clear) High risk (Allocation was based on odd/even number already known by trialist) Participants: High risk Providers: High risk Outcome assessors: unclear risk 22.7% (high risk) No (high risk) No (low risk) Unclear risk (Home BP not able to be calculated due to insufficient information on baseline data in paper) Not stated (unclear risk) Summary Citation & location design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Puska et al. (1983), Finland [] parallel design study II Adults (aged 30-50 years), mixed and hypertensive Participants were randomised to either: 1. low fat diet (25% energy from fat) 2. low salt diet (reduced from following advice from Blood pressure (seated after 5 min rest) 107 (n=72 in groups 2 and 3) 6 weeks All participants: Low sodium period: 77 + 5mmol/24hr (p<0.001) Normal sodium period: 167 + 8mmol/24hr Mean difference between low sodium period and normal sodium period: SBP: 0.1mmHg 6.48)
dietitians & provision of low salt 3. control (maintain usual diet) (note only groups 2 and 3 used in analysis by Graudal) DBP: -0.7mmHg (CI: -5.22, 3.82) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Puska et al. (1983) Unclear risk (randomisation method not stated) Unclear risk (method of concealment of allocation not described, stratified by locality and age) Participants: unclear risk Providers: high risk Outcome assessors: low risk 6.1% (low risk) No (unclear risk) No (low risk) Yes (low risk) US Department of Agriculture (low risk) Summary table
et al. (1993), Spain Unclear risk (randomisation method not stated) Unclear risk (method of concealment of allocation not described, stratified by locality and age) Participants: unclear risk Providers: high risk Outcome assessors: low risk >45% (many excluded due to compliance cut-offs) – high risk No (high risk) No (low risk) Yes (low risk) Not stated (unclear risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Richards et al. (1984), New Zealand [] study II Adults (aged 19-52 with mild essential hypertension (140/90 – Participants were randomised to start one of three arms: control diet (180mmol sodium/day and 60mmol potassium/day) pressure (supine after 20 min rest, standing after 5 min), 24 hr. ambulatory pressure (during period) 12 4 - 6 weeks Low sodium diet: 100mmol/24hr Normal sodium diet: 200mmol/24hr (p<0.001) Note: estimated from figure Mean difference between low sodium period and normal sodium period: SBP: -4mmHg (SEM: 2.79, CI: -9.47, 1.47) out
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results Ruppert et al. (1993), Germany [] study II Adults (aged 27 – 75 years) who had previously participated in one week study of NaCl and placebo (cannot be included in current analysis due to duration) All participants were instructed to consume a diet containing 85mmol sodium/day. Participants were then randomised to start one of two cross-over arms: 1. Restricted sodium diet plus NaCl capsules (total daily sodium intake: 200mmol/day) 2. Restricted sodium diet plus placebo daily sodium intake: 85mmol/day) Blood pressure (supine after 30 min rest), mean arterial pressure, total cholesterol, LDL, HDL 25 4 weeks Low sodium diet: 82 + 3.4mmol/24hr Normal sodium diet: 199.6 + 5.3 mmol/24hr (p<0.001) Mean difference between low sodium period and normal sodium period: SBP: 1.70mmHg (CI: 8.38) DBP: (CI: -3.47, 5.47) Cholesterol: 0.00mmol/L (CI: -0.46, 0.46) HDL:-0.04mmol/L (CI: 0.15) LDL: 0.13mmol/L (CI: 0.54) (All values from WHO) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of Ceasing study Reporting all outcome results Funding source
DASH 2001 - Sacks et al. (2001) - Vollmer et al. (2001) - Harsha et al. (2004) USA [, , ] study II Adults (22 and older), normotensive and hypertensive (SBP: 120 – 159mmHg, DBP: 80 – 95mmHg) Participants consumed a high sodium (150mmol/day) control diet for a 2 week run-in period. They were then randomised to either a control diet (usual USA style diet) or DASH. Participants in both diet groups were then randomised to start one of three cross-over arms: 1. Low sodium (50mmol/day) plus DASH or control diet 2. Intermediate sodium (100mmol/day) plus DASH or control diet SBP (primary outcome), DBP (BP measured seated), serum total cholesterol, HDL and LDL 390 30 days Control diet: Low sodium diet: 64 + 37mmol/24hr Normal sodium diet (Intermediate dietary period): 106 + 44 mmol/24hr DASH diet: Low sodium diet: 67 + 46mmol/24hr Normal sodium diet (Intermediate dietary period): 107 + 52 mmol/24hr Mean difference between low sodium period and normal sodium period (intermediate period) Control diet: SBP: (CI: -5.9, -3.2) DBP: -2.4mmHg (CI: -3.3, DASH diet: SBP: (CI: -3.0, -0.4) DBP: -1.0mmHg (CI: -1.9, Control diet: Cholesterol: 0.07mmol/L (CI: -0.02, 0.15) HDL: -0.01mmol/L (CI: -0.03, 0.01) LDL: 0.07mmol/L (CI: 0.00, 0.15) DASH diet:
3. High sodium (150mmol/day) plus DASH or control diet Cholesterol: 0.04mmol/L (CI: -0.04, 0.13) HDL: 0.01mmol/L (CI: -0.02, 0.03) LDL: 0.01mmol/L (CI: -0.06, 0.09) Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing early for benefit Reporting all outcome results Funding source DASH 2001 - Sacks et al. (2001) - Vollmer et al. (2001) - Harsha et al. (2004) Low risk (computer generated sequence used) Low risk (Allocation occurred at central location) Participants: High risk Providers: high risk Outcome assessors: low risk 5.4% loss to follow-up (low risk) Yes (low risk) No (low risk) Yes (low risk) National Heart, Lung and Blood Institute, General Clinical Research Center Program of the National Center for Research Resources (low risk)
Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results TOHP, Phase I -Whelton et al. (1992) et al. (1993) -Whelton et al. (1997a) USA [, , ] parallel design study II Adults (30 – 54 years), with high normal diastolic blood pressure (mean: in sodium reduction group and in control) Participants were randomly assigned to either lifestyle (18 months) or supplement interventions (6 months each, compared with placebo): Lifestyle 1: weight reduction (group and individual education) Lifestyle 2: sodium reduction (group and individual education) Lifestyle 3: stress management (group and individual education) Lifestyle 4: usual care Supplement 1: calcium Supplement 2: magnesium Supplement 3: fish oil Supplement 4: potassium BP (seated 5 min rest) (note DBP was primary outcome, SBP secondary outcome) 744 (in sodium reduction and control groups, n=2182 for total study) 18 months Mean difference in the change in urinary sodium excretion between groups (active – control): -43.86 (CI: -30.84) mmol/24hr (p<0.01) Mean difference between sodium reduction and control period: SBP: (SEM: 0.59, CI: -2.86, -0.54) DBP: (SEM: 0.42, CI: -1.62, 0.02)
TOHP, I -Whelton et al. (1992) Kumanyika et al. (1993) -Whelton et al. (1997a) Unclear risk (method of randomisation not described) Low risk (Concealment of allocation at a central location) Participants: unclear risk Providers: high risk Outcome assessors: low risk <5% loss to follow-up (low risk) Yes (low risk) No (low risk) Yes (low risk) National Heart, Lung, and Blood Institute, National Institutes of Health (low risk) Summary table Citation & location design level of Population Intervention Outcomes measured relevant to research question Sample size duration Compliance to sodium target (urinary data) Results TOHP, Phase II -Whelton et al. (1997b) USA [] parallel design II Moderately overweight adults (30 – 54 years), with high normal diastolic blood pressure (mean DBP:86.1mmHg in sodium reduction group Participants were randomly assigned to one of four treatment groups: 1. weight loss (goal achievement of desirable body weight or mean weight loss of at least 4.5kg) (group and individual education) BP (seated) (note DBP was primary outcome, SBP secondary outcome) 1190 36 – 48 months Mean difference in the change in urinary sodium excretion between groups (active – control): -40.4 + 5.7 (p<0.001) Mean difference between sodium reduction and control period: SBP: (SEM: 0.52, CI: -2.02, 0.02) DBP: -0.5mmHg (SEM: 0.4, CI: -1.28, 0.28)
TOHP, II Unclear risk (method of randomisation not described) Low risk (Concealment of allocation at a central location) Participants: unclear risk Providers: high risk Outcome assessors: low risk <5% loss to follow-up (low risk) Yes (low risk) No (low risk) Yes (low risk) National Lung, and Blood Institute, National Institutes of Health (low risk) Summary table Citation & location Study design level of Population Intervention measured relevant to research question Sample size Compliance to sodium target (urinary data) Results Schorr et al. placebo II Normotensive adults (aged Participants were all counselled to reduce dietary salt intake to <100mmol/day prior Resting BP, lipids, 24 hour 16 4 weeks per 24 hour urinary Comparison between high sodium chloride and placebo treatment (from Graudal which compared
(1996), Germany [] cross to interventions (participants remained on low salt diet for study duration) Participants randomised in order to consume 1.5L of a mineral water with the following composition: NaCl rich (sodium 84.5mmol/l, chloride 63.7mmol/l, bicarbonate 21.9mmol/l) Sodium bicarbonate rich: (sodium 39.3mmol/l, chloride 6.5mmol/l, bicarbonate <0.02mmol/l BP excretion data: 1.High NaCl mineral water treatment: 2. High sodium bicarbonate mineral treatment: 3. Low sodium & bicarbonate (placebo), mineral water treatment: high sodium chloride treatment and placebo): SBP: -1mmHg (SEM:2.7, 95%CI: 4.29) DBP: (SEM: 1.73, 95%CI: 3.39) Insufficient BP data to work change between bicarbonate rich treatment and either SBP, DBP or 24 hour ambulatory BP (data given as day and night time 24 hour ambulatory BP or a figure without further detail) Change in Total Cholesterol between high NaCL mineral water and placebo treatments: 5 mg/dl (95%CI:-20.93, 30.93) Change in HDL-cholesterol 3mg/dl (95%CI: -2.97, 8.97) Change in LDL cholesterol: 7mg/dl (95%CI: -15.59, 29.59) Baseline total cholesterol:
Schorr et al. (1996) Unclear (no description of method of sequence generation) Unclear (not described) Participants: blinded, low risk Providers: blinded, low risk Outcome assessors: unclear 19.2% (loss of 5), data only analysed for considered compliant, high risk No, high risk No (Low risk) Unclear, some data missing (eg. Baseline ambulatory BP) Unclear, not specified Summary table Citation & location Study design NHMRC level of evidence Population Intervention Outcomes measured relevant to research question size duration Compliance to sodium target (urinary data) Results Sciarrone et al (1992), Australia [] Randomised parallel, double blind placebo controlled (with a 2x2 factorial design) II 95 hypertensive adults, some on medication (mean BP 137/83mmHg) – now considered Participants prescribed a low sodium diet (target <60mmol/day) and randomised to one of two groups: Low sodium, low fat, high SBP (supine & resting), DBP (supine & resting), Total cholesterol, HDL cholesterol, LDL cholesterol 95 (4 drop outs but data for all 8 weeks 24 hour urinary sodium excretion: Low sodium diet: hours (CI: 42.9, 61.2) (data provided grouped both low Data grouped according to sodium intake: Change in relevant outcomes: Normal sodium (n=21) & low sodium
high normal BP), mean age: 53.5 years N=79 participants were undergoing treatment and were asked not to change medication for study duration fibre diet (<60mmol sodium/day; 30% energy from fat, P:S ratio=1, fibre/day) Low sodium, normal fat, normal fibre (<60mmol sodium/day; 40% energy from fat; P:S ration=0.3, 15g fibre/day) Half of each treatment group were then randomised to receive either 100mmol NaCl tablets per day or a placebo sodium arms together) Normal sodium diet: 133.9mmol/24 hours (CI: 125.4, 142) (data provided grouped both normal sodium arms together) (n=27) groups (both low fat/high dietary prescription): SBP: -7.5mmHg (95%CI: -13.19, -1.81) DBP: (95%CI: 2.74) Total cholesterol: 0.00mmol/l(95%CI: 0.54) HDL-C: -0.10mmol/l (95%CI: -0.21, 0.01) LDL-C: 0.10mmol/l (95%CI: 0.57) Normal sodium (n=24) & low sodium (n=19) groups (both normal fat/normal dietary prescription):
Sciarrone et al (1992) Unclear (no description of method of sequence generation) Unclear (not described) Participants: blinded, Low risk Providers: blinded, Low risk Outcome assessors: unclear <5%, Low risk No, unclear No (Low risk) Yes (Low risk) NHMRC, Royal Perth Hospital research funding Summary Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Silman et al (1983), UK [] design II Adults aged 50-64 years, with DBP for past 13 months, not taking Participants were randomised to either: Low sodium diet: (aim 100mmol sodium/day) based on dietary advice Control: Standard monitoring of BP, SBP, DBP (method described as ‘the standard way’) 28 participants randomised 1 year Low sodium diet group: At 12 months: 117mmol/24 hours (based on available urinary data for 7 out of 12 participants), mean change from baseline: Mean changes between low sodium and control groups: SBP: 3.5mmHg (SEM: 11.39, 95%CI: -18.82, 25.82)
excretion data (unclear) Providers: not blinded Outcome assessors: unclear Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Singer et al (1991), UK [] cross over placebo cross II Adults with essential hypertension (mean age 53±2.5 taking captopril (50mg twice daily) and (diuretic) 25mg/day for at least a Whilst remaining on medications (and following 1 run in phase of usual diet), participants were instructed by a dietitian to reduce dietary sodium (aim 80-100mmol/day) for two weeks prior to SBP, DBP, MAP 21 4 weeks per treatment 24 hour urinary sodium excretion: Low treatment: High sodium treatment: Comparison between change in placebo and high sodium treatments (supine BP): SBP: -9mmHg (SEM: 3, 95%CI: -14.88, -3.12)
Singer et al (1991) Unclear (no description of method of sequence generation) Unclear (not described) Participants: blinded, low risk Providers: Blinded, low risk Outcome assessors: unclear 0% drop outs, Low risk Low risk (no drop outs) No (Low risk) Unclear, baseline MAP data not provided Unclear (not specified) Summary Citation & location design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Suckling et al. (2010), UK abstract) [] cross over study II Adults with type 2 diabetes or impaired glucose tolerance, with untreated Participants were randomised to the following interventions: Reduced sodium diet + (unspecified amount of slow SBP, DBP (measured in a clinic), 24 hour ambulatory BP, urinary albumin excretion 46 6 weeks 24 hour urinary sodium excretion for: High sodium group: 165±9mmol/day Control (placebo) Mean difference between groups: SBP: -4.3mmHg (95% CI:-9.71, 1.11) (from WHO SLR) DBP: -1.6mmHg (95%CI: -4.79, 1.59) (From WHO SLR)
normal or high BP sodium tablets/day) Reduced sodium diet + placebo (control group) 117±10mmol/day No baseline data to calculate change in ambulatory BP Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Suckling et al (2010) *conference abstract Unclear (not enough information in abstract) Unclear (not enough information in abstract) Participants: unclear Providers: Unclear Outcome assessors: Unclear Unclear unclear Unclear Unclear Unclear Summary table
Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Compliance to sodium target (urinary data) Results Swift (2005), UK [] double blind, placebo cross II African or African descent (mean age 50±10 years), not taking medication DBP ≥90mmHg) Mean SBP 156±12, mean DBP Following a run in period on usual diet, then advice to reduce salt intake to 5g/day, Participants were randomised to one of two groups: 1.Reduced sodium (low salt diet + placebo tablets) 2. Higher sodium (low salt diet + 120mmol/day slow sodium tablets) in a cross over design Blood pressure (measured by a nurse), 24 hour ambulatory BP 46 randomised, 40 completed 4 weeks urinary sodium excretion in study groups: Higher sodium 169±73mmol/24 hours Placebo (lower sodium) group: 89±52mmol/24 hours Mean fall in urinary sodium excretion was 78±62mmol.24 (P<0.001) Mean changes between low sodium and higher sodium groups (based on supine BP): SBP: (SEM: 2.06, 95%CI: -12.04, -3.96) DBP: -3mmHg (SEM: 1.11, 95%CI: -5.18, -0.82) *no baseline 24 hour ambulatory BP available to calculate change
Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Swift et al (2005) Unclear (method of randomisation not described) Low risk (pharmacy conducted) Participants: blinded, Low risk Providers: blinded to allocation, Low risk Outcome assessors: unclear 7 lost (1 during phase, 6 following 14% (low risk) Only reported data from participants that completed the study, but unlikely to affect results, Low risk No (Low risk) unclear, reported baseline total cholesterol, triglycerides but no data post intervention, also 24hr ABP baseline data not provided Placebo & slow sodium tablets provided by CIBA, unlikely conflict, Low risk(low risk) Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to Sample size duration Compliance to sodium target (urinary data) Results
research question Van (2004), USA [] cross study II Middle aged adults with mild, borderline hypertension (not on medication for duration of trials) (BP –Grade 1– grade 2) Participants were randomised to either: Low sodium diet: target <40mmol/day High sodium diet: target >225mmol/day Participants also maintained sodium intakes of: during the first and third 4 week periods All sodium targets were achieved through intensive BP, SBP, MAP, cholesterol 48 4 weeks (4x 4 week periods) Mean 24 hour urinary sodium excretion: Low sodium diet: 24±13mmol/day High sodium diet: 309±88mmol/day Change in SBP between low sodium & higher sodium diets: -16mmHg (SEM: 1.51, 95%CI: -18.96-13.04) Change in DBP between diets: -8mmHg (SEM: -10.04, 95%CI: -5.96) Insufficient baseline data to calculate change in MAP Change in total cholesterol between low sodium & high sodium diets: 3mg/dl(95%CI: -11.82, 17.82) (from Graudal)
counselling with a dietitian Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Van et al. (2004) Unclear (no description of method of sequence generation) Unclear (not described) Participants: received dietary counselling, high risk Providers: not blinded, high risk Outcome assessors: Unclear Low risk Low risk No (Low risk) Yes (low risk) NIH Summary table Citation & location design level of Population Intervention Outcomes measured relevant to Sample size Intervention duration Compliance to sodium target (urinary data) Results
research question Watt et al, (1983), Wales [] Double blind, cross over II Adults aged between with stable hypertension (mean BP 144/93 mmHg) not taking medication Participants were provided with dietary advice and access to to reduce total sodium intake for the duration of the intervention periods (8 weeks in total), participants were randomised to either: Higher sodium diet: Provided with 8x slow sodium tablets/day (total 80mmol/sodium) Or Placebo group: Provided with 8x placebo tablets SBP, DBP (measured seated), MAP 18 (2 drop outs, data presented for those that completed only) 4 weeks (per intervention) Mean 24 hour urinary excretion for the higher sodium diet: 143mmol/day Mean 24 hour urinary excretion for the placebo 87mmol/day Mean changes between placebo and higher sodium groups: SBP: (SEM: 1.5, 95%CI: -3.44, 2.44) DBP: -0.3mmHg (SEM: 0.8, 95% CI: -1.87, 1.27) MAP data entered into excel spreadsheet (SD data available)
Key features for bias assessment of randomised trials Citation Method of randomisation Allocation concealment Blinding Loss to Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Watt et al. (1983) Unclear (methods of randomisation not described) Unclear Participants: Low risk Providers: Low risk Outcome assessors: unclear Low risk (two participants lost one from each group) Unclear No (Low risk) Yes (Low risk) British Heart Foundation Summary table Citation & location Study design level of Population Intervention Outcomes measured relevant to research question Sample size Intervention duration Compliance to sodium target (urinary data) Results Watt et al. (1985), Double blind, cross II Adults aged 22-23 years, and determined from a All participants were randomly allocated to a cross-over arm for SBP, DBP (measured seated), MAP 66 (statistical analyses were conducted 4 weeks each intervention arm Data presented based on the two groups: Group 1 (low risk for HT): 128.4mmol Mean changes between placebo and higher sodium group (for low
research question Weir et al. (2010), USA [] blinded end point cross over study II Adults with hypertension (range SBP aged 16-60 years, taking 300mg/day aliskiren (direct renin inhibitor for treatment of HT) Participants were randomised to intervention groups in a cross design (no washout period) Low sodium diet (≤100mmol sodium/day), dietitian advice provided High sodium diet (≥200mmol sodium/day), dietitian advice provided Resting BP, 24 hour ambulatory BP 132 4 weeks per Mean 24 hour urinary sodium excretion: Low sodium diet: 84.8mEq sodium/ 24 hours High sodium diet: 207.6mEq sodium/24 hours (P<0.0001) Difference in resting SBP between groups: -9.4mmHg (0.97SEM, 95%CI: -11.3, -7.50) Difference in resting DBP between groups: -5.7mmHg (0.66SEM, 95%CI: -4.41) maDBP was lower with the lower sodium diet compared to the higher sodium diet (LSM difference: 5.7mmHg, 95%CI, 4.4-6.9, p<.0001) (raw data entered into excel sheet) maSBP was lower with the low sodium diet compared with the high sodium diet (LSM difference: 9.4mmHg, 95%ci: 7.5-11.4) (raw data entered into excel sheet) Key features for bias assessment of randomised trials
Citation Method of randomisation Allocation concealment Blinding Loss to follow-up Use of where required Ceasing study early for benefit Reporting all outcome results Funding source Weir et al. (2010) Unclear (no methods given) High risk (no method of concealment used) Participants: Not blinded, high risk Providers: not blinded, high risk Outcome assessors: not blinded, high risk <15% Low risk (loss to follow up between groups), low risk Unclear No (Low risk) All outcomes reported, low risk Novartis Pharmaceuticals Corporation, unclear
Jablonski et al. (2013) ? ? + + ? ? ? + + + McCarron et al. (1997 + ? + + + + + + ? + Meland et al. (1997) ? ? + + ? + + + + + Meland et al. (2009) ? + + + ? + + + + + Ruppert et al. (1993) ? ? + + ? + + + + ? DASH 2001 + + - - + + + + + + Schorr et al. (1996) ? ? + + ? - - + ? ? Sciarrone et al (1992) ? ? + + ? + ? + + + Figure 10: Risk of bias assessment summary, HDL cholesterol Table 5: Brief summary of bias assessment (GRADE) – LDL cholesterol Citation Method of Allocation Blinding (pts) Blinding (provider) Blinding (outcome assessor) Loss to Use of where required Ceasing early for benefit all results Funding source Fotherby et al (1993) and Fotherby et al (1997) ? ? + + ? + ? + + + Gates et al. (2004) ? ? + + ? + + + + + Jablonski et al. (2013) ? ? + + ? ? ? + + + McCarron et al. (1997 + ? + + + + + + ? +
Appendix 7: GRADE evidence profile Quality assessment No of patients Effect Quality No of studies Design Risk of bias Inconsistency Indirectness Imprecision Other A low intake of sodium A high intake of sodium Absolute systolic blood pressure (all participants) (follow-up 4 - 156 weeks; measured with: resting; Better indicated by lower values) 61 trials no serious risk of bias1 serious2 no serious indirectness3 no serious imprecision4 none5 3592 3634 MD 3.9 lower (4.7 to 3 lower)  systolic blood pressure (HT participants only) (follow-up 4 - 104 weeks; measured with: resting; Better indicated by lower values) 42 trials no serious risk of bias no serious inconsistency7 no serious indirectness no serious imprecision8 none9 1672 1609 MD 4.7 (5.8 to 3.6 lower)  HIGH systolic blood pressure (NT participants only) (follow-up 6 - 156 weeks; measured with: resting; Better indicated by lower values) 13 trials no serious risk of bias no serious inconsistency10 no serious indirectness no serious imprecision11 none12 1394 1495 MD 1.0 (1.8 to 0.2 lower)  HIGH systolic pressure (mixed hypertension status) (follow-up 4 - 6 weeks; measured with: resting; Better indicated by lower values) 6 trials no serious risk of bias serious13 no serious indirectness no serious imprecision14 none15 526 530 MD 4.4 lower (6.7 to 2.1 lower)  Total cholesterol (follow-up 4 - 8 weeks; Better indicated by lower values) 16 trials no serious risk of bias no serious inconsistency16 no serious indirectness no serious imprecision17 none18 804 803 MD 0.03 higher (0.02 lower to 0.08 higher)  HIGH