Effect of Low-Sodium Salt Substitutes on Blood Pressure ...
Transcript of Effect of Low-Sodium Salt Substitutes on Blood Pressure ...
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Effect of Low-Sodium Salt Substitutes on Blood Pressure, Detected
Hypertension, Stroke and Mortality
A Systematic Review and Meta-analysis of Randomized Controlled Trials
AV Hernandez et al. on November 30, 2018
Online-only Supplement
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Supplementary Methods: PubMed Search Strategy
Supplementary Reference List of included randomized controlled trials Table S1. Characteristics of included randomized controlled trials
Supplementary Figures of main analyses:
Figure S1:Flow diagram of study selection
Figure S2:Risk of bias of included studies
Figure S3:Effect of salt substitutes on overall mortality
Figure S4:Effect of salt substitutes on urinary calcium excretion (mmol/day)
Figure S5:Effect of salt substitutes on glucose (mmol/L)
Figure S6:Effect of salt substitutes on total cholesterol (mmol/L)
Figure S7:Effect of salt substitutes on triglycerides (mg/dL)
Figure S8: Effect of salt substitutes on BMI (kg/m2)
Supplementary Figures of Subgroup analyses:
Figure S9: Effect of salt substitutes on SBP by subgroup of duration of intervention (≤3months
vs >3 months).
Figure S10: Effect of salt substitutes on DBP by subgroup of duration of intervention
(≤3months vs >3 months).
Figure S11: Effect of salt substitutes on detected hypertension by subgroup of duration of
intervention (≤3months vs >3 months) in hypertensive populations.
Figure S12: Effect of salt substitutes on urinary sodium excretion by subgroup of duration of
intervention (≤3months vs >3 months) in hypertensive populations.
Figure S13: Effect of salt substitutes on urinary potassium excretion by subgroup of duration of
intervention (≤3months vs >3 months) in hypertensive populations.
Figure S14: Effect of salt substitutes on urinary calcium excretion by subgroup of duration of
intervention (≤3months vs >3 months) in hypertensive populations.
Figure S15: Effect of salt substitutes on total cholesterol by subgroup of duration of intervention
(≤3months vs >3 months) in hypertensive populations.
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Figure S16: Effect of salt substitutes on triglycerides by subgroup of duration of intervention
(≤3months vs >3 months) in hypertensive populations.
Supplementary Figures of Sensitivity analyses:
Figure S17: Effect of salt substitutes on SBP excluding high risk of bias trials.
Figure S18: Effect of salt substitutes on DBP excluding high risk of bias trials.
Figure S19: Effect of salt substitutes on detected hypertension excluding high risk of bias trials
in hypertensive populations.
Figure S20: Effect of salt substitutes on urinary sodium excretion excluding high risk of bias
trials in hypertensive populations.
Figure S21: Effect of salt substitutes on urinary potassium excretion excluding high risk of bias
trials in hypertensive populations.
Figure S22: Effect of salt substitutes on urinary calcium excretion excluding high risk of bias
trials in hypertensive populations.
Figure S23: Effect of salt substitutes on glucose excluding high risk of bias trials in
hypertensive populations.
Figure S24: Effect of salt substitutes on total cholesterol excluding high risk of bias trials in
hypertensive populations.
Figure S25: Effect of salt substitutes on triglycerides excluding high risk of bias trials in
hypertensive populations.
Figure S26: Effect of salt substitutes on BMI excluding high risk of bias trials in hypertensive
populations.
Meta-regression analyses Methods of meta-regression analyses
Figure S27: Mean difference of SBP (salt substitutes vs control) by mean age
Figure S28: Mean difference of SBP (salt substitutes vs control) by % of female
Figure S29: Mean difference of SBP (salt substitutes vs control) by baseline mean BP
Figure S30: Mean difference of SBP (salt substitutes vs control) by %NaCl content of salt
substitute.
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Figure S31: Mean difference of DBP (salt substitutes vs control) by mean age
Figure S32: Mean difference of DBP (salt substitutes vs control) by % of female
Figure S33: Mean difference of DBP (salt substitutes vs control) by baseline mean BP
Figure S34: Mean difference of DBP (salt substitutes vs control) by %NaCl content of salt
substitute.
Correlations between change in urinary Na/ K excretion and change in SBP/DBP per trial arm
Methods of correlation analyses
Figure S35: Correlation between change in urinary Na and change of SBP per trial arm
Figure S36: Correlation between change in urinary Na and change of DBP per trial arm
Figure S37: Correlation between change in urinary K and change of SBP per trial arm
Figure S38: Correlation between change in urinary K and change of DBP per trial arm
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Supplementary Methods: PubMed search strategy (salt substitution OR salt substitute OR low-sodium salt substitute OR salt replacing OR salt
replacement OR salt replacer OR salt reduction OR salt reducer OR Low-So salt replacer OR
KcLean salt OR Kalisel OR Salt Trim OR Lacto Optitaste OR Pansalt OR Sub4salt OR
LomaSalt OR Saltwise OR Myciscent OR Salt reducer N100 OR Salt reducer N200 OR Dr
Lohmann’s Premix salt replacer OR AlsoSalt OR Nu-Tek’s modified potassium chloride OR
Soda-Lo OR Zalt OR Maxorite delite OR Maxarite Bsalt OR Maxarite Dsalt OR Maxarome
select OR Maxarome pure OR KojiAji OR Ajimate super RK OR Ajinomoto OR SaltAnswer
OR Super YE OR Fonterra Savoury Powder OR Flavour intensifier OR Savoury Flavour
enhancer OR Flavour enhancer OR SavourCrave OR UnSal20 OR Seagreens Organic
Mineral Salt OR Sense Capture Salt OR potassium OR magnesium OR KCl OR MgCl) AND
(healthy OR normotension OR prehypertension OR hypertension OR obesity OR type 2
diabetes OR stroke) AND blood pressure AND randomized controlled trial AND humans
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Supplementary reference list of included randomized controlled trials w1. Arzilli F, Taddei S, Graziadei L, et al. Potassium-rich and sodium-poor salt reduces blood
pressure in hospitalized patients. Journal of hypertension Supplement : official journal of
the International Society of Hypertension 1986;4:S347-50.
w2. Suppa G, Pollavini G, Alberti D, et al. Effects of a low-sodium high-potassium salt in
hypertensive patients treated with metoprolol: a multicentre study. Journal of hypertension
1988;6:787-90.
w3. Geleijnse JM, Witteman JC, Bak AA, et al. Reduction in blood pressure with a low sodium,
high potassium, high magnesium salt in older subjects with mild to moderate
hypertension. Bmj 1994;309:436-40.
w4. Omvik P, Myking OL. Unchanged central hemodynamics after six months of moderate
sodium restriction with or without potassium supplement in essential hypertension. Blood
pressure 1995;4:32-41.
w5. Gilleran G, O'Leary M, Bartlett WA, et al. Effects of dietary sodium substitution with
potassium and magnesium in hypertensive type II diabetics: a randomised blind controlled
parallel study. Journal of human hypertension 1996;10:517-21.
w6. Mu JJ, Liu ZQ, Yang J, et al. [Long term observation in effects of potassium and calcium
supplementation on arterial blood pressure and sodium metabolism in adolescents with
higher blood pressure]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive
medicine] 2003;37:90-2.
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w7. Chang HY, Hu YW, Yue CS, et al. Effect of potassium-enriched salt on cardiovascular
mortality and medical expenses of elderly men. The American journal of clinical nutrition
2006;83:1289-96.
w8. Pereira MA, Galvao R, Zanella MT. Effects of potassium supplementation by salt on
arterial blood pressure and insulin resistance in hypertensive obese patients on diuretic
therapy. Rev Nutr 2005;18:5-17.
w9. China Salt Substitute Study Collaborative G. Salt substitution: a low-cost strategy for blood
pressure control among rural Chinese. A randomized, controlled trial. Journal of
hypertension 2007;25:2011-8.
w10. Mu J, Liu Z, Liu F, et al. Family-based randomized trial to detect effects on blood pressure
of a salt substitute containing potassium and calcium in hypertensive adolescents.
American journal of hypertension 2009;22:943-7.
w11. Sarkkinen ES, Kastarinen MJ, Niskanen TH, et al. Feasibility and antihypertensive effect
of replacing regular salt with mineral salt -rich in magnesium and potassium- in subjects
with mildly elevated blood pressure. Nutrition journal 2011;10:88.
w12. Zhou X, Liu JX, Shi R, et al. Compound ion salt, a novel low-sodium salt substitute: from
animal study to community-based population trial. American journal of hypertension
2009;22:934-42.
w13. Allaert FA. Double-blind, randomized, crossover, controlled clinical trial of NaCl +
Chitosan 3% versus NaCl on mild or moderate high blood pressure during the diet and
lifestyle improvement period before possible prescription of an antihypertensive treatment.
International angiology : a journal of the International Union of Angiology 2013;32:94-
101.
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w14. Zhou B, Wang HL, Wang WL, et al. Long-term effects of salt substitution on blood
pressure in a rural north Chinese population. Journal of human hypertension 2013;27:427-
33.
w15. Barros CL, Sousa AL, Chinem BM, et al. Impact of light salt substitution for regular salt
on blood pressure of hypertensive patients. Arquivos brasileiros de cardiologia
2015;104:128-35.
w16. Zhao X, Yin X, Li X, et al. Using a low-sodium, high-potassium salt substitute to reduce
blood pressure among Tibetans with high blood pressure: a patient-blinded randomized
controlled trial. PloS one 2014;9:e110131.
w17. Li N, Yan LL, Niu W, et al. The Effects of a Community-Based Sodium Reduction
Program in Rural China - A Cluster-Randomized Trial. PloS one 2016;11:e0166620.
w18. Yang GH, Zhou X, Ji WJ, et al. Effects of a low salt diet on isolated systolic hypertension:
A community-based population study. Medicine 2018;97:e0342.
w19. Allaert FA. Effect of NaCl + Chitosan 3% vs. NaCl on high blood pressure parameters of
healthy volunteers with prehypertension. Minerva cardioangiologica 2017;65:563-76.
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Supplementary Table 1. Characteristics of included randomized controlled trials
Study Name, Year (reference)
Study Years
Study Location
Phase Follow up time (mo.)
Population, baseline mean BP (mmHg)
Total Sample Size (salt substitute /control group)
Salt substitute name [composition] (dose)
Control salt name [composition] (dose)
Mean age (SD)
% Male
Outcomes Evaluated
Arzilli F 1986 (w1)
N/A Italy 2 0.25 Mild hypertension & hospitalized MBP: 127
10 (5/5) K/Na Salt [NaCl 50%, KCl 25% and K3C6H5O6 15%] (2g twice daily added to standard diet [20 mmol Na + 4g common salt])
Common Salt [N/A] (2g twice daily added to standard diet [20 mmol Na + 4g common salt])
Mean (range): 39.5 (28-53)
60 SBP, DBP, Na & K urinary excretion (24-h sample) No harms reported
Suppa G 1988 (w2)
N/A Italy 2 1 All hypertensive MBP: 113
322 (163/159)
Novosalt®
[NaCl 50%, KCl 25%, K3C6H5O7 15%] (2g twice daily added to lunch and dinner [34 mmol Na and 19.3 mmol K]; amount of salt for cooking and foods unchanged)
Common Salt [NaCl 100%] (2g twice daily added to lunch and dinner; amount of salt for cooking and foods unchanged)
Substitute: 47.1 (9.8) Control: 47.8(10.1)
62.7 SBP, DBP, Na & K urinary excretion (24-h sample) No harms reported
Geleijnse JM 1994
(w3)
1990-1992
Netherlands
2 6 Mild to moderate hypertensive, no previous treatment MBP: 113
100 (49/51)
SagaSalt®
[NaCl 41%, KCl 41%, Mg salts 17% and minerals 1%] (Salt for cooking and at the table and foods; Na/K ratio in foods: 1.3 to 1.8 mmol/mmol)
Common Salt [NaCl] (Salt for cooking and at the table and foods; Na/K ratio in foods: 6.7 to 22.7 mmol/mmol)
Substitute: 65.7 (4.6) Control: 67.1 (4.5)
51 Na, K & Ca urinary excretion (24-h sample) No harms reported
Omvik P 1995 (w4)
N/A Norway 2 6
All hypertensive
40 (20/20) Pansalt®
[NaCl 57%, KCl 28%, Standard Sodium Chloride
Substitute: 45.9 (N/A)
68 Hypertension, SBP, DBP, Na &
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MBP: 124
MgSO4 12%, lysine 2%] (Salt used in small amounts as cooking and table salt replacing household salt. Diet with 30% sodium restriction)
[N/A] (Salt used in small amounts as cooking and table salt replacing household salt. Diet with 30% sodium restriction )
Control: 42.7 (N/A)
K urinary excretion (24-h sample) No harms reported
Gilleran G 1996 (w5)
N/A United Kingdom
2 3 Type 2 diabetics, mild hypertensive MBP: 118
40 (20/20) Seltin®
[NaCl 50%, KCl 40%, MgSO4 10%] (Salt replaced household salt; patients used added salt at the table or in the cooking before trial)
Ordinary Table Salt. [N/A] (Salt replaced household salt; patients used added salt at the table or in the cooking before trial)
Substitute: 62.5 (7.8) Control: 59.2 (10.8)
60 SBP, DBP, Na & K urinary excretion (24-h sample), total cholesterol, triglycerides No harms reported
Mu JJ 2003 (w6)
N/A (pending)
China 2 24 All hypertensive MBP: 92
220 (110/110)
Supplementary salt [10mmol of K and 10mmol of Ca salt] (Mixed in the table salt)
Regular salt [N/A] (Table salt)
Mean: 20.6 (2.1)
51.8 SBP, DBP No harms reported
Pereira M 2005 (w8)
N/A Brazil 2 3 All hypertensive MBP: 108
22 (12/10)
N/A [NaCl 50% and KCl 50%] (Salt replaced household salt)
Common Salt [NaCl 100%] (Salt replaced household salt)
Mean: 47.5 (11.2)
14 SBP, DBP, total cholesterol, triglycerides, BMI, waist circumference No harms reported
Chang HY
2006 (w7) 1995-1999
Taiwan 2 44 General population 40% hypertensive
1981 (768/1213)
K Enriched Salt [NaCl 49%, KCl 49% and other additives 2%] (Replaced regular salt in cooking gradually,
Regular Salt [NaCl 99.6% and other additives 0.4%] (Regular salt in cooking at all times.
Substitute: 74.8 (7.1) Control: 74.9 (6.7)
N/A CVD mortality No harms reported
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MBP: 91 from a KES/RS 1:3 ratio to 100% KES. Daily Na intake was 3.8g; 30% from sauces)
Daily Na intake was 5.2g; 30% from sauces)
Li N 2007 (w9)
2004- 2005
China 2 12 All hypertensive MBP: 115
608 (306/302)
N/A [NaCl 65%, KCl 25% and MgSO4 10%] (Cooking, pickling and other uses within household; ≤ 3kg salt per month. Existing salt and food previously pickled not removed )
N/A [NaCl 100%] (Cooking, pickling and other uses within household; ≤3kg salt per month. Existing salt and food previously pickled not removed)
Mean: 60 (10)
44 SBP, stroke, overall mortality Harms: No patients with severe hyperkalemia in both arms
Mu J 2009
(w10) N/A China 2 24 General
population, mixed hypertensive MBP: 92
215 (101/114)
N/A [Salt with added KCl and CaCl2] (10 mmol KCl and 10 mmol CaCl2 added per day to usual salt consumption. Na intake 144±44 mmol/day at 6mo)
N/A [N/A] (Usual salt consumption. Na intake 127±31 mmol/day at 6mo)
Substitute: 20.3 (3.1) Control: 21.4 (3.9)
53.5
SBP, DBP Harms: No patients with severe hyperkalemia in both arms
Zhou X (a) 2009 (w12)
N/A China 2 6 All hypertensive MBP: 108
126 (62/62)
CiSalt®
[NaCl 65%, KCl 30%, Calcium salts 5% and 12mg/kg folic acid] (All cooking and other uses replacing regular salt. ≤3kg per month)
NSalt [NaCl 100%] (All cooking and other uses. ≤3kg per month )
Substitute: 67.5 (5.2) Control: 65.7 (6.3)
42 SBP, DBP, Glucose, Na & K & Ca urinary excretion (24-h sample), total cholesterol, triglycerides No harms reported
Zhou X (b) 2009 (w12)
2003- 2004
China 2 6 Normotensive
122 (57/65)
CiSalt®
[NaCl 65%, KCl 30%, NSalt [NaCl 100%]
Substitute: 68.1 (8.3)
45 SBP, DBP, Glucose, Na & K
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MBP: 91
Calcium salts 5% and 12 mg/kg folic acid] (All cooking and other uses replacing regular salt. ≤3kg per month)
(All cooking and other uses. ≤3kg per month )
Control: 65.4 (4.5)
& Ca urinary excretion (24-h sample), total cholesterol, triglycerides No harms reported
Sarkkinen ES 2011 (w11)
N/A Finland 2 2 All hypertensive (130-159/85-99 mmHg) MBP: 105
45 (22/23) Smart Salt®
[NaCl 50%, KCl 25%, magnesal 25%] (Used for cooking and baking as well as table salt; 6.8±3.3 g NaCl intake per day )
Regular Salt [NaCl 100%] (Used for cooking and baking as well as table salt; 10.1±3.1 g NaCl intake per day)
Substitute: 57 (12) Control: 54 (11)
51.1 SBP, DBP, Na & K urinary excretion (24-h sample), BMI No harms reported
Allaert FA 2013 (w13)
N/A France 2, cross-over
2 Mild hypertension, no previous treatment MBP: 112
40 (19/21) Symbiosal®
[NaCl 97% and chitosan 3%] (max 3g per day, added to regular salt intake)
Standard NaCl sea salt [NaCl 100%] (max 3g per day, added to regular salt intake)
Mean: 58.6(12)
40 Hypertension, SBP, DBP No harms reported
Zhou B 2013 (w14)
N/A China 2 24 General population, mixed hypertensive MBP: 111
462 (224/238)
Salt substitute [NaCl 65%, KCl 25%, MgSO4 10%] (Salt used to prepare all foods)
Normal Salt [NaCl 100%] (Salt used to prepare all foods)
Mean: 46 (16)
49 SBP, DBP No harms reported
Zhao X 2014 (w16)
2009 China 2 3 All hypertensive MBP: 129
282 (141/141)
Salt Substitute [NaCl: 65%, KCl: 25%, MgSO4: 10%] (20±5.4g average per family daily NaCl consumption)
Regular salt [NaCl 100%] (26.9±8.1g average per family daily NaCl consumption)
Substitute: 62.8 (11.1) Control: 63.5 (11.3)
41.1 Hypertension, SBP, DBP No harms reported
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Barros CL 2015 (w15)
2012 Brazil 2 1 All hypertensive MBP: 108
35 (19/16) Light Salt®
[Na: 130mg/g, K: 346mg/g, I: 44mcg/g] (3g per day; consumed only provided salt; reduced sodium-rich food consumption during study)
‘Regular salt’ [Na: 390mg/g, I: 25mcg/g] (3g per day; consumed only provided salt; reduced sodium-rich food consumption during study)
Mean: 55.5 (7.4)
34.3 SBP, DBP, Na & K urinary excretion (24-h sample), BMI No harms reported
Li N 2016 (w17)
2011- 2012
China 3- Clustered
18 General population, township MBP: 105
2566 (1294/1272)
Salt substitute [NaCl 65%, KCl 25%, MgSO4 10%] (Available at shops; Used to replace all household salt use –cooking, pickling, discretionary mealtime use-)
Regular salt [NaCl 100%] (Available at shops; Use for all household salt use)
Substitute: 55 (15) Control: 55 (14)
50 Hypertension, SBP, DBP, Na & K urinary excretion (24-h sample), BMI No number of patients with harms reported. No difference between arms for hyperkalemia or renal failure.
Allaert FA 2017 (w19)
N/A France 2 2 Pre-hypertension (SBP 130-139 mmHg; DBP: 80-89 mmHg) MBP: 99
41 (22/19) Symbiosal®
[NaCl 97% and chitosan 3%] (max 3g per day {table salt consumption 2.2±1.1 g/day}, added to regular salt intake; no change in nutritional habits during study)
Standard NaCl sea salt [NaCl 100%] (max 3g day {table salt consumption 2.5±1.2 g/day}, added to regular salt intake; no change in nutritional habits during study)
Mean: 51 (16)
51.2 SBP, DBP No harms reported
Yang G-H 2018 (a) (w18)
N/A China 2 6 Isolated systolic hypertension (ISH;
51 (24/27) LSSalt (Low sodium salt) [NaCl 65%, KCl 30%, Ca salts 5% and
NSalt (Regular salt) [NaCl 100%] (Used for regular salt consumption)
Substitute: 67.8 (5.3) Control: 65.9 (6.2)
41.2 SBP, DBP, Na, K, & Ca urinary excretion (24-h sample), total
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SBP≥140 mmHg & DBP<90 mmHg) MBP: 107
12mg/kg folic acid] (Used for regular salt consumption)
cholesterol, triglycerides No harms reported
Yang G-H 2018 (b) (w18)
N/A China 2 6 Non-ISH (NISH; SBP≥140 mmHg & DBP≥90 mmHg) MBP: 109
75 (38/37) LSSalt (Low sodium salt) [NaCl 65%, KCl 30%, Ca salts 5% and 12mg/kg folic acid] (Used for regular salt consumption)
NSalt (Regular salt) [NaCl 100%] (Used for regular salt consumption)
Substitute: 67.3 (5.6) Control: 65.4 (6.8)
44 SBP, DBP, Na, K, & Ca urinary excretion (24-h sample), total cholesterol, triglycerides No harms reported
SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure; BMI: body mass index; Na: Sodium; K: Potassium; Ca: Calcium; Mg: magnesium, I: Iodine; ISH: isolated systolic hypertension; N/A: Not available. Harms of interest included hyponatremia, hyperkalemia, renal failure, and sudden death.
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Supplementary Figures Figure S1. Flow diagram of study selection
Included
Eligibility
Screening
Identification Records identified through
database searching: 3081
Records after duplicates removed: 2572
Records screened by title/abstract Records excluded: 2543
Full text articles assessed for eligibility: 29
RCTs included in qualitative synthesis: 21
(19 articles)
RCTs included in quantitative synthesis: 21
(19 articles)
Reasons for full text article exclusion:
Lack of outcomes (n=7)Duplicated data (n=3)
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Figure S2. Risk of bias of included studies
a. Risk of bias Summary format
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b. Risk of bias Study-specific format
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Figure S3. Effect of salt substitutes on overall mortality
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Figure S4. Effect of salt substitutes on urinary calcium excretion (mmol/day)
21
Figure S5. Effect of salt substitutes on glucose (mmol/L)
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Figure S6. Effect of salt substitutes on total cholesterol (mmol/L)
23
Figure S7. Effect of salt substitutes on triglycerides (mg/dL)
24
Figure S8. Effect of salt substitutes on BMI (kg/m2)
25
Figure S9: Effect of salt substitutes on SBP by subgroup of duration of
intervention (≤3months vs >3 months).
26
Figure S10: Effect of salt substitutes on DBP by subgroup of duration of
intervention (≤3months vs >3 months).
27
Figure S11: Effect of salt substitutes on detected hypertension by subgroup of
duration of intervention (≤3months vs >3 months) in hypertensive populations.
28
Figure S12: Effect of salt substitutes on urinary sodium excretion by subgroup of
duration of intervention (≤3months vs >3 months) in hypertensive populations.
29
Figure S13: Effect of salt substitutes on urinary potassium excretion by subgroup
of duration of intervention (≤3months vs >3 months) in hypertensive populations.
30
Figure S14: Effect of salt substitutes on urinary calcium excretion by subgroup of
duration of intervention (≤3months vs >3 months) in hypertensive populations.
31
Figure S15: Effect of salt substitutes on total cholesterol by subgroup of duration
of intervention (≤3months vs >3 months) in hypertensive populations.
32
Figure S16: Effect of salt substitutes on triglycerides by subgroup of duration of
intervention (≤3months vs >3 months) in hypertensive populations.
33
Figure S17: Effect of salt substitutes on SBP excluding high risk of bias trials.
34
Figure S18: Effect of salt substitutes on DBP excluding high risk of bias trials.
35
Figure S19: Effect of salt substitutes on detected hypertension excluding high
risk of bias trials in hypertensive populations.
36
Figure S20: Effect of salt substitutes on urinary sodium excretion excluding high
risk of bias trials in hypertensive populations.
37
Figure S21: Effect of salt substitutes on urinary potassium excretion excluding
high risk of bias trials in hypertensive populations.
38
Figure S22: Effect of salt substitutes on urinary calcium excretion excluding high
risk of bias trials in hypertensive populations.
39
Figure S23: Effect of salt substitutes on glucose excluding high risk of bias trials
in hypertensive populations.
40
Figure S24: Effect of salt substitutes on total cholesterol excluding high risk of
bias trials in hypertensive populations.
41
Figure S25: Effect of salt substitutes on triglycerides excluding high risk of bias
trials in hypertensive populations.
42
Figure S26: Effect of salt substitutes on BMI excluding high risk of bias trials in
hypertensive populations.
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Methods of meta-regression analyses
Meta-regressionanalyseswereperformedtoevaluatethevariabilityofMDofbloodpressurebetween
saltsubstitutesandcontrolgroupsbysomestudyvariablessuchasmeanage,proportionoffemale,and
baselinemeanbloodpressure.Meta-regressionswerebasedonlinearregressionsofMD,whichwere
calculatedinrandomeffectsmeta-analyseswiththeinversevariancemethodandtheDerSimonian-
Lairdestimatorsfortau2.TwoMDswereevaluated:SBPandDBP.Theinfluenceofastudyvariableon
theMDwasquantifiedastheslopeofthelinearregressionmodel;alsotheR2(i.e.variabilityofMD
explainedbythestudyvariable)andpvalueswerecalculated.Themetaregcommandofthemeta
packageofR3.5.1(www.r-project.org)wasusedforallanalyses.
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Figure S27: Mean difference of SBP (salt substitutes vs control) by mean age
MDdecreasesby0.05perincreaseinoneyearofage(R2=0.01,p=0.4)
Covariate mage
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
20 30 40 50 60
−12
−10
−8−6
−4
45
Figure S28: Mean difference of SBP (salt substitutes vs control) by % of female
MDdecreasesby0.1perincreaseinonepercentoffemale(R2=0.01,p=0.3)
Covariate pfemale
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
30 40 50 60 70 80
−12
−10
−8−6
−4
46
Figure S29: Mean difference of SBP (salt substitutes vs control) by baseline mean
BP
MDincreasesby0.01perincreaseinonemmHgofbaselinemeanBP(R2=0.001,p=0.9)
Covariate bmbp
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
90 100 110 120 130
−12
−10
−8−6
−4
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Figure S30: Mean difference of SBP (salt substitutes vs control) by %NaCl
content of salt substitute.
MDdecreasesby0.02perincreaseinonepercentofcontentofNaClinsaltsubstitute(R2=0.01,p=0.6)
Covariate naclperc
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
0 20 40 60 80 100
−12
−10
−8−6
−4
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Figure S31: Mean difference of DBP (salt substitutes vs control) by mean age
MDdecreasesby0.007perincreaseinoneyearofage(R2=0.002,p=0.9)
Covariate mage
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
20 30 40 50 60
−6−4
−20
49
Figure S32: Mean difference of DBP (salt substitutes vs control) by % of female
MDdecreasesby0.07perincreaseinonepercentoffemale(R2=0.03,p=0.2)
Covariate pfemale
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
30 40 50 60 70 80
−6−4
−20
50
Figure S33: Mean difference of DBP (salt substitutes vs control) by baseline mean
BP
MDincreasesby0.05perincreaseinonemmHgofbaselinemeanBP(R2=0.02,p=0.4)
Covariate bmbp
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
90 100 110 120 130
−6−4
−20
51
Figure S34: Mean difference of DBP (salt substitutes vs control) by %NaCl
content of salt substitute.
MDdecreasesby0.01perincreaseinonepercentofcontentofNaClinsaltsubstitute(R2=0.005,p=0.7)
Covariate naclperc
Trea
tmen
t effe
ct (m
ean
diffe
renc
e)
0 20 40 60 80 100
−6−4
−20
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MethodsofcorrelationanalysesWeevaluatedthecorrelationbetweenurinaryNaorKchangeandSBPorDBPchangepertrialarm.
BothSpearmancorrelationcoefficientsandscatterplotswereweightedbythesamplesizeofarms.The
ggplot2andwCorrpackagesofR3.5.1(www.r-project.org)wereusedforallanalyses.
Figure S35: Correlation between change in urinary Na and change of SBP per trial
arm
Weighted Spearman correlation coefficient: 0.56, p=0.01
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Figure S36: Correlation between change in urinary Na and change of DBP per trial
arm
Weighted Spearman correlation coefficient: 0.45, p=0.03
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Figure S37: Correlation between change in urinary K and change of SBP per trial
arm
Weighted Spearman correlation coefficient: -0.49, p=0.07
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Figure S38: Correlation between change in urinary K and change of DBP per trial
arm
Weighted Spearman correlation coefficient: -0.39, p=0.2