Benet assessment of salt reduction in patients with

hypertension: systematic overview

Eva Matyas
a
, Klaus Jeitler
a,b
, Karl Horvath
a
, Thomas Semlitsch
a
,
Lars G. Hemkens
c
, Nicole Pignitter
a
and Andrea Siebenhofer
d
Objective We assessed the benets and harm of reduced
salt intake in patients with essential hypertension focusing
on patient-relevant outcomes and blood pressure.
Methods A systematic search of ve electronic databases
was performed to identify high-quality secondary literature
based on randomized controlled trials (RCTs). An
update primary literature search (RCTs) was performed for
the time period up to 2010 that was not covered by
secondary literature. Major outcomes were death,
cardiovascular morbidity/mortality, hospital stays, terminal
renal failure, quality of life, and adverse events. Change in
blood pressure was dened as surrogate parameter.
Results Four different systematic reviews and two RCTs
met the inclusion criteria. Only one review reported limited
data on patient-relevant outcomes. Over an intervention
period of up to 12 months, mean SBP was reduced by
3.68.0mmHg in all reviews. For the same intervention
period, a statistically signicant advantage with regard to
mean DBP reduction ranging from 1.9 to 2.8mmHg was
found in three reviews. The fourth publication reported a
nonsignicant reduction (DBP reduction of 4.7mmHg).
None of the RCTs identied in the primary literature search
update reported data on patient-relevant outcomes.
However, both RCTs found blood pressure improvements
with salt reduction.
Conclusion A benet from a salt-reduced diet in patients
with high blood pressure is not proven with regard to
patient-relevant outcomes based on systematic reviews
and RCTs published up to 2010. The results indicate a blood
pressure-lowering effect through reduced salt intake in
hypertensive patients. J Hypertens 29:821828 Q 2011
Wolters Kluwer Health | Lippincott Williams & Wilkins.
Journal of Hypertension 2011, 29:821828
Keywords: diet, dietary, hypertension, sodium, sodium-restricted
Abbreviations: HTA, health technology assessment; IQWiG, Institute for
Quality and Efciency in Healthcare; RCTr, andomized controlled trial
a
Department of Internal Medicine, EBM Review Center Medical University of
Graz,
b
Institute for Medical Informatics, Statistics and Documentation, Medical
University of Graz, Graz, Austria,
c
Institute for Quality and Efciency in Healthcare
(IQWiG), Cologne and
d
Institute of General Practice, Goethe University
Frankfurt, Frankfurt, Germany
Correspondence to Andrea Siebenhofer, MD, Institute of General Practice,
Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
Tel: +49 69 6301 7296; fax: +49 69 6301 6428;
e-mail: siebenhofer@allgemeinmedizin.uni-frankfurt.de
Received 23 June 2010 Revised 14 December 2010
Accepted 28 December 2010
See editorial comment on page 829
Introduction
Hypertension is a chronic condition associated with an
increased risk of cardiovascular mortality and morbidity.
High blood pressure is estimated to lead to over 7 million
deaths each year, about 13%of the total deaths worldwide
[1]. Lowering blood pressure levels in hypertensive
patients has been shown to be a very effective means
of reducing those patients cardiovascular risk, with a
signicant reduction in cardiovascular morbidity and
mortality [2,3].
The main treatments available for essential hypertension
are blood pressure-lowering drugs and various nondrug
treatment options. Consistently, epidemiological inves-
tigations have found an association between high blood
pressure and different lifestyle factors, high sodium
intake among them [47]. This assumption was also
underlined by some recently published systematic
reviews, including randomized controlled trials (RCTs)
showing that salt reduction also lowered blood pressure
[810]. In addition, higher salt intake was found to be
associated with increased cardiovascular events [11].
National and international professional associations
recommend the consistent, long-term implementation
of nondrug measures in the treatment of essential hyper-
tension. Reduced salt intake is recommended in major
guidelines as one of the rst-line interventions in the
treatment of hypertensive patients [1216].
This investigation is based on a report of the Institute for
Quality and Efciency in Healthcare in Germany
(IQWiG), which aimed to assess the benets and harm
of reduced salt intake. This report incorporated existing
systematic reviews. According to the IQWiG methods
[17], such an approach is deemed as resource-saving and
reliable, provided that specic preconditions have been
fullled (see below). Such overviews, sometimes called
umbrella reviews or meta-reviews, which combine and
compare different systematic reviews assessing interven-
tions, have recently been adopted by the Cochrane
Collaboration as well [18]. The present publication on
reduced salt intake is part of a package of systematic
Review 821
0263-6352 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/HJH.0b013e3283442840
benet assessments on different lifestyle interventions.
Results based on previous reports on the effect of weight
reduction have already been published [1921] and
further reports, for example, on physical activity and
alcohol reduction are in preparation. The present inves-
tigation aimed to review systematically the benets and
harm of different interventions involving salt reduction
in patients with essential hypertension according to
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement [22].
Methods
Eligibility of publications
The investigation included systematic reviews of RCTs
of at least 4 weeks duration involving nonpregnant
patients aged 18 years or older with essential hyperten-
sion. The intervention to be tested in these trials was a
reduction in salt intake compared to no such reduction in
salt intake or a lower intended salt intake in the inter-
vention group than in the control group. Any additional
(antihypertensive) treatment had to be given equally in
both groups. Excluded were systematic reviews and
health technology assessment (HTA) reports in which
the reduction in salt intake as a primary intervention was
compared to another antihypertensive treatment as a
primary intervention (e.g., reduced salt intake versus diet
or versus blood pressure-lowering drugs).
Outcomes of interest
The evaluation focused on patient-relevant therapy out-
comes (mortality, cardiovascular morbidity and mortality,
hospital stays, terminal renal failure, capacity for work,
health-related quality of life, patient satisfaction, and
adverse events) and blood pressure as a surrogate end-
point in hypertensive people. Patient-relevant therapy
goals and surrogates were prospectively dened in a
protocol and detailed criteria for assessment of the
patient-relevant endpoints were determined in accord-
ance with the IQWiG methods Version 3.0 [17].
Selection of publications and methods of assessment
As indicated in the Cochrane Handbook [18] and IQWiG
methods Version 3.0 [17], the preparation of a review on
the basis of secondary literature is feasible, if major key
elements are considered as detailed in Table 1 in the
Appendix, http://links.lww.com/HJH/A71.
The bibliographic databases EMBASE and MEDLINE,
and three databases of the Cochrane Library [HTA
Database, The Cochrane Database of Systematic
Reviews (CDSR), Database of Abstracts of Reviews of
Effects (DARE)] were searched for related reviews
published after the year 1997 up to February 2010. All
systematic reviews published in English, German,
French, or Spanish were included. In addition, a primary
literature search update restricted to English and German
publications in EMBASE, MEDLINE/PubMed and
the Cochrane Central Register of Controlled Trials
(CENTRAL) was performed only for the time period
that was not covered by secondary literature. As the last
primary literature search in the systematic reviews was
performed in 2005, we searched for RCTs published
between 2005 and February 2010.
The search strategy is published in detail in the IQWiG
report [23]. Titles and abstracts were screened indepen-
dently by multiple teams of two reviewers (K.H., K.J.,
T.W.G., E.M. and/or A.S.); potentially relevant second-
ary publications were assessed as full texts by the same
reviewers. Differences between reviewers were resolved
by discussion or a third reviewer was involved. The
methodological quality assessment of the relevant
reviews was done according to Oxman and Guyatts index
[24,25]. Systematic reviews were included if they scored
at least ve out of seven possible points.
Identical inclusion criteria as for the systematic reviews
were used to identify relevant RCTs. The quality assess-
ment of the included RCTs was based on randomization,
blinding, allocation concealment, intention-to-treat
analysis, and further aspects of bias risk, and was con-
ducted independently by K.H. and E.M., who graded the
relevant RCTs as having no (A), moderate (B), or serious
(C) methodological deciencies.
Results
Results from the secondary literature
We identied 1729 potentially relevant publications in
the secondary literature and seven systematic reviews
[810,2629] met the inclusion criteria. All of those were
assessed with at least ve out of seven possible points by
the Oxman and Guyatts score. These publications were
allocated to four groups of authors and included 62 RCTs
overall (Fig. 1 in the Appendix, http://links.lww.com/
HJH/A71). Table 1 [810,28] in the text gives an over-
view of the included systematic reviews. The search
strategies, selection criteria used for inclusion of primary
studies, number and duration of included RCTs, and the
patient characteristics are shown (Table 1 in the text). In
addition, Table 2 of the Appendix, http://links.lww.com/
HJH/A71 provides an outline of the database of relevant
outcomes within the systematic reviews.
Two systematic reviews (Hooper et al. [28] and Dickinson
et al. [8]) aimed for patient-relevant outcomes, but only
Hooper et al. [28] reported relevant patient-related out-
comes such as mortality, cardiovascular events, quality of
life, and adverse events. None of the reviews reported
data on hospital stays, terminal renal failure, capacity for
work, or patient satisfaction (Table 2 in the Appendix,
http://links.lww.com/HJH/A71). Results of the review
published by Hooper et al. [28] are described in the
following: data on all-cause mortality were provided for
three out of eight primary studies. One study reported
four deaths in the intervention and ve deaths in the
822 Journal of Hypertension 2011, Vol 29 No 5
control group (Morgan et al. [30]), whereas the other two
studies counted no death (Alli et al. [31] and TONE
[32,33]). Cardiovascular events were described in two
(Alli et al. [31] and TONE [32,33]) out of eight studies
and the presented meta-analysis showed no signicant
difference between the salt-reduced and control groups
(Hooper et al. [28]). In the review of Hooper et al. [28],
health-related quality of life was described in only one
trial (Thaler et al. [34]). Data were not scaled by a
conventional measurement and it was not possible to
compare the study groups. Adverse events were reported
in two studies within the 2004 review by Hooper et al. In
the study by Thaler et al. [34], muscle cramps were more
frequent in the intervention group. As the difference
between the groups with regard to frequency of muscle
cramps was similar at study entry (29.5% in the inter-
vention group versus 15.3% in the control group), there
was no evidence of an increase in muscle cramps. A
statistically signicant smaller number of participants
in the salt-reducing group reported headache in the
TONE trial [32,33], but further details necessary to
interpret this nding were not reported.
For investigations on blood pressure as a surrogate, most
of the analyses showed a blood pressure-lowering effect
in hypertensive patients through reduced salt intake
when compared to a control treatment (Fig. 1 in the text;
Table 3 in the Appendix, http://links.lww.com/HJH/A71).
Over an intervention period of up to 12 months, the
analyses showed a statistically signicant difference
with regard to mean SBP reduction ranging from 3.6 to
8.0mmHg in favor of the intervention groups. For the
same intervention period, a statistically signicant differ-
ence with regard to mean DBP reduction ranging from
1.9 to 2.8mmHg was found in three reviews. In the
fourth publication (Hooper et al. [28]), a more pronounced
reduction was also observed for the intervention (differ-
ence of 4.7mmHg compared to control treatment),
but this was based on only four trials and without
statistical signicance. All data primarily apply to analyses
of patients without concomitant antihypertensive drug
treatment.
In the study by Dickinson et al. [8], results on blood
pressure were based on a meta-analysis of six studies
including 450 untreated patients and showed no hetero-
geneity. There was a statistically signicant weighted
mean difference in studies lasting from 8 to 52 weeks in
favor of the salt-reduced group. Including only studies
with a duration of at least 6 months, there was no longer
any statistically signicant weighted mean difference.
Similar effects in untreated hypertensive patients favor-
ing the intervention group were obtained in the meta-
analysis lasting between 4 and 52 weeks of follow-up of
Benefit assessment of salt reduction in hypertension Matyas et al. 823
Table 1 Characteristics of the systematic reviews/number and duration of the included relevant randomized controlled trials
Systematic review Relevant selection criteria Search
Number/duration
(median) of
included RCTs
Patient
characteristics
Dickinson et al. [8]; Sponsoring:
National Institute for Clinical
Excellence (NICE)
Inclusion criteria: RCTs;
duration 8 weeks; adults;
SBP 140 and/or DBP
85mmHg; exclusion criteria:
pregnancy; secondary
hypertension; change in
antihypertensive medication
during follow-up
MEDLINE (1998 to May 2003);
EMBASE (1998 to May 2003);
CENTRAL (1998 to May 2003);
references of hypertension
guidelines, systematic reviews
and meta-analyses (before 1998)
8 RCTs, 8 to
52 weeks
(52 weeks)
Number of patients:
520; mean %
female: 24; mean
age: 52 years; mean
BP: 151/95mmHg
He and MacGregor [9]
(Update 2006); Sponsoring:
no sponsor
Inclusion criteria: RCTs; duration:
4 weeks; age 18 years;
net reduction in 24-h urinary
sodium must be equal to or
greater than 40mmol; exclusion
criteria: pregnancy
MEDLINE (1966 to April 2005);
EMBASE (1980 to April 2005);
CINHAL (1982 to June 2001);
Cochrane Library (up to April
2005); references of original
articles and reviews
20 RCTs, 4 to
52 weeks
(5 weeks)
Number of patients:
802; Median %
female: 47 (range:
1576); median
age: 50 years;
median BP:
149/94mmHg
Hooper et al. [28]; Sponsoring:
NW Research Development
Training Fellowship
Inclusion criteria: RCTs; duration
26 weeks; age 16 years;
exclusion criteria: pregnancy,
hospitalized patients
MEDLINE (up to July 2000);
EMBASE (up to July 2000);
Cochrane Library (up to July
2000); CAB abstracts,
CVRCT registry, SIGLE (up
to May 1998); bibliographies
of identied publications
and reviews
8 RCTs, 6 months
to 7 years
(12 months)
Number of patients:
1188; median %
female: 50 (range:
058); Mean age:
n.a.; median BP:
145/86mmHg
Ju rgens and Graudal [10];
Sponsoring: no sponsor
Inclusion criteria: RCTs, additional
interventions had to be
comparable in the intervention
groups; at least 8h urinary
sodium excretion; age >15 years;
exclusion criteria: pregnancy
MEDLINE (1966 to December
2001); EMBASE, CCTR
(no data of search
time available)
54 RCTs, 4 to
365 days
(28 days)
Number of patients:
n.a.
a
; % female: n.a;
mean age: 49 years;
mean BP: n.a.
BP, blood pressure; n.a., no data available; RCT, randomized controlled trial.
a
In the meta-analyses, n3391 (DBP) and n3367 (SBP) were included. These numbers
also include cross-over comparisons and several primary studies <4 weeks of duration.
He et al. [9], including 20 comparisons with about 800
patients. There was marked heterogeneity in the blood
pressure results and possible reasons given by the authors
were differences between studies in age, ethnic group,
baseline blood pressure levels, the amount and the
duration of salt intake reduction, and the study quality.
They did not perform further sensitivity analyses due to
the small number of trials and the very limited infor-
mation reported in the studies.
A meta-analysis by Hooper et al. [28] containing four
studies lasting between 6 and 12 months of follow-up
covering 179 hypertensive patients without antihyper-
tensive drug treatment showed a statistically signicant
advantage in favor of the intervention group for the SBP
only. There was moderate heterogeneity (P0.15;
I
2
43%). For DBP, there were two studies with the
same follow-up period with 87 untreated hypertensive
patients that only showed a trend in favor of the inter-
vention group. Hooper et al. identied only one small trial
(Morgan et al. [30,35]) with 62 patients lasting more than a
year in which only the DBP was signicantly reduced due
to salt reduction. In addition, Hooper et al. [28] included
three studies with treated hypertensive patients as well,
but the authors did not explain why a meta-analysis was
not performed. One of these trials (TONE [32,33]) did
not report any blood pressure results. In a study by
Morgan and Anderson [36], in which antihypertensive
drug treatment was withdrawn after 3 months in both
groups, after 9 months of follow-up, blood pressure
increased less under salt reduction. In the study by Arroll
and Beaglehole [37], there was a greater mean decrease
after 6 months of intervention for SBP in the salt-reduced
group than in the control group [9.1 (standard deviation
21.7); 6.2 (standard deviation 21.0) mmHg]. For DBP,
the mean decrease was smaller in the salt-reduced group
824 Journal of Hypertension 2011, Vol 29 No 5
Fig. 1
Systematic
review
Dickinson 2006
8
He 2004
9
Hooper 2004
28
Jrgens 2004
10
SBP
6
19
4
53
5.3 (6.7; 3.9)
8.0 (15.8; 0.2)
4.2 (5.1; 3.3)
Weighted mean difference (95% CI)
[mmHg]
RCTs
[n]
DBP
6
20
4
54
2.5 (3.2; 1.7)
2.8 (3.6; 2.0)
4.7 (9.3; 0.04)
1.9 (2.5; 1.3)
Weighted mean difference (95% CI)
[mmHg]
RCTs
[n]
15 0 15
Favours salt reduction Favours control
15 0 15
Favours salt reduction Favours control
3.6 (4.6; 2.5)
Weighted mean differences for SBP and DBP: comparison of the results for the follow-up up to 12 months.
Table 2 Characteristics of the randomized controlled trials from primary literature search update
RCT
Relevant selection
criteria
Study design/
duration of study Intervention Patient characteristics Outcomes
He and MacGregor
[38]; Sponsoring:
UK Food
Standards Agency
Inclusion criteria: age:
3075 years; SBP
140170 or DBP
90105mmHg; exclusion
criteria: pregnancy, previous
treatment for raised BP;
secondary hypertension,
previous stroke, ischemic
heart disease, heart failure,
diabetes mellitus,
malignancy or liver disease;
women on oral contraceptives
RCT; double-blind;
cross-over/
6 weeks
2 weeks run-in phase
on a reduced-salt diet;
IG: 9 slow sodium
tablets (10mmol per
tablet) daily; CG:
9 placebo tablets daily
No separate analyses for
IG and CG available;
number of patients:
169; % female: n.a.;
mean age: 50 years;
mean BP:
147/91mmHg
Patient-relevant endpoints:
n.a.; surrogate endpoints:
duration and extent of
blood pressure changes;
BP at study end [mean
difference (mmHg]: SBP:
4.8 (95%CI: 6.4 to
3.2); P<0.001; DBP:
2.2 (95%CI: 3.1 to
1.4); P<0.001]
Meland and Aamland
[39]; Sponsoring:
Norske Hoechst
AS, University
of Bergen
student grant,
Solstrandsfondet
Inclusion criteria: age:
2075 years, patients on
antihypertensive drugs;
SBP 160210 and/or DBP
90115mmHg; exclusion
criteria: drug-induced
hypertension; use of
antihypertensives due to
other cardiovascular
illnesses
RCT; double-blind;
parallel/8 weeks
Salt-reduced diet in both
groups; IG: 5 capsules
of 10mmol sodium/day;
CG: 5 placebo capsules
/day (identical capsules
to IG)
Number of patients
IG/CG: 57/55;
% female: n.a;
mean age: IG/CG:
57/55 years; mean
BP: IG/CG; SBP:
157/155mmHg;
DBP 93/92mmHg
Patient-relevant endpoints:
n.a.; surrogate endpoints:
duration and extent of
blood pressure changes;
BP at study end [mean
difference (mmHg): SBP:
5 (95%CI: 11 to 0);
P<0.07; DBP: 5
(95% CI: 7 to 1);
P<0.02
CG, control group; CI, condence interval; IG, intervention group; n.a., no data available; RCT, randomized controlled trial.
than in the control group [1.7 (standard deviation 34.9);
4.8 (standard deviation 36.1) mmHg].
In the fourth systematic review including 54 studies
(Ju rgens and Graudal [10]), no separate analyses for
treated and untreated hypertensive people were per-
formed. For both SBP including 3391 participants in
the analysis and for the DBP including 3367 participants,
there was a signicant weighted mean difference in favor
of the intervention group. There was no signicant
heterogeneity found for either of the blood pressure
analyses.
Results from randomized controlled trials published
between 2005 and 2010
The primary literature search update revealed 573
additional references. Two RCTs [38,39] were included
in this systematic overview. The trial ow is given in
Fig. 2 in the Appendix, http://links.lww.com/HJH/A71.
Table 2 [38,39] in the text provides information on
relevant characteristics of the included RCTs. The qual-
ity assessment of these two studies is presented in
Table 4 in the Appendix, http://links.lww.com/HJH/
A71; one was judged to have moderate and the other
one serious risk of bias.
Both trials lasted only a fewweeks and no data on patient-
relevant outcomes were reported. However, blood pres-
sure changes were shown in both studies and indicated a
benet in the salt-reduced patient groups. The results in
the study by He et al. [38] showed a statistically signi-
cant difference in SBP and DBP between the inter-
vention and the control groups [SBP: 4.8 mmHg
(95% condence interval 6.4 to 3.2); P<0.001;
DBP: 2.2 mmHg (95% condence interval 3.1 to
1.4); P<0.001]. In the study by Meland and Aamland
[39], there was a statistically signicant difference
between the groups in favor of the intervention group
only in the DBP [5 mmHg (95% condence interval 7
to 1); P<0.02]. For the SBP, the difference was not
statistically signicant [5 mmHg; (95% condence
interval 11 to 0); P<0.07; see Table 2 in the text].
Discussion
Based on high quality secondary literature and an exten-
sive update search for RCTs, we conducted a systematic
overview examining the question of whether salt
reduction in patients with essential hypertension is
benecial or harmful. The robustness of the results
appears plausible as this overview covers the high quality
evidence available to date, and a primary literature search
update was performed. Within the systematic reviews
included, no primary study was identied in which the
primary objective was to investigate the reduction in salt
intake as an intervention in order to prevent patient-
relevant complications. In relation to blood pressure, all
analyses showed a blood pressure-lowering effect in
hypertensive patients through reduced salt intake when
compared to a control treatment. The reported extent of
the effect size varied among the reviews.
Our ndings are not unexpected against the background
of the epidemiological data suggesting that salt intake
is positively associated with blood pressure levels
[11,4144]. None of the RCTs included in the identied
systematic reviews was powered to detect a potential
benet indicating that salt-reduced diet decreases unfa-
vorable patient-relevant outcomes. Consequently, evi-
dence for the assumption that salt restriction is associated
with a tremendous reduction in cardiovascular outcomes
as well, is only based on epidemiological observations
[11,41,45]. In the recently published systematic review
and meta-analysis of prospective studies published by
Strazzullo et al. in 2009 [11], including 19 independent
cohort samples with more than 170 000 participants and a
follow-up between 3.5 and 19 years, higher salt intake
was associated with a signicantly greater risk of stroke
(pooled relative risk 1.23; 95% condence interval 1.06
1.43; P0.007) and a tendentially higher, though non-
signicant, risk of cardiovascular disease was observed
(pooled relative risk 1.14, 95% condence interval 0.99
1.32; P0.07). In a recently published narrative review,
multiple studies have shown that the adjusted relative
risk reduction in controlled observational studies aiming
for reduced sodium intake ranged from 25% over 15 years
to 41% over 3 years [45]. The effect of a direct application
of a salt reduction in daily life has been demonstrated
in an RCT, which investigated the Dietary Approaches
for Stop Hypertension (DASH) diet, rich in fruits and
vegetables and low-fat diary products in combination
with reduced dietary sodium uptake. In patients having
such a diet, it has been shown that the SBP was
11.5 mmHg lower compared to patients with control diet
with high sodium intake [46]. It has been reported that
this blood pressure reduction has been further improved
when patients on the DASH diet additionally exercise
and follow a weight management program [47].
This evidence is further underlined in a long-term obser-
vational follow-up study of two hypertension prevention
trials (TOHP I and II) with prehypertensive patients.
This study does not meet the inclusion criteria of our
review; however, as long-term results are of major
relevance in this context, we would like to discuss them
in further detail. A total of 3126 patients randomly
assigned to salt restriction in TOPH I and TOPH II
were observed for a further 1015 years after the end of
the original RCTs lasting for 1848 months. Follow-up
information on cardiovascular outcomes was 77% and for
death 100%, and blinded endpoint evaluation by medical
records was performed. In this long-term observation, the
risk of a cardiovascular event was about 2530% lower
among those in the salt-reduced group and there was a
trend to a lower mortality rate, which was, however, not
statistically signicant [48]. On the basis of those studies,
reduced salt intake is recommended by many leading
Benefit assessment of salt reduction in hypertension Matyas et al. 825
national and international professional associations
[1216]. There is solid evidence for a health benet
when blood pressure is reduced to recommended levels,
and in certain patients, lifestyle changes may enable
them to reduce or stop drug therapy as well [32]. In
terms of salt intake, experts in this eld advise patients to
rst decrease their consumption of processed food, refrain
from adding salt, and eat more fruits and vegetables [49].
Limitations of our overview are that most of the RCTs
included in the systematic reviews provided only a small
number of patients and short follow-up. As a consequence,
none had the power to evaluate patient-relevant outcomes
and no answer can be provided on these aspects. In
addition, the included systematic reviews differ in their
chosen outcomes, inclusion criteria, and search strategies,
which also might cause the differences in the numbers of
studies included in the systematic reviews. Although we
included only high quality systematic reviews, another
limitation is that the reviews might have some aws that
are passed over to our review as well. Nonetheless, the
results obtained in terms of blood pressure point in the
same direction, which once again further conrms the
assumptions known for a long time that dietary salt restric-
tion appears to be effective with regard to this surrogate.
However, animportant limitationis that almost noneof the
analyses presented results on patients who were simul-
taneously taking antihypertensive drugs, and an additional
blood pressure-lowering capacity in those patients taking
suchmedicationremains unclear. This needs to beempha-
sized as this raises the question whether the results are
generalizable to patients being treated with antihyper-
tensive drugs. In addition, only one (Hooper et al. [28])
of the four included systematic reviews presented some
limited information on how salt intake was reduced with
the different interventions. This in turn means that no
recommendations canbe givenonthe basis of these results
as to how salt intake should best be reduced. Moreover,
valid long-term data are not available and well founded
information on patient-relevant outcomes does not exist.
The importance of this uncertainty is emphasized by an
example from a study with successful weight reduction.
The Swedish Obese Subject Study (SOS) in which more
than 1700 patients successfully reduced their body weight
by means of bariatric surgery has shown that the initial
postsurgical bloodpressurereductionwas still present after
2 years, but was almost gone 10 years later [50]. In terms of
adverse events, Klaus et al. [45] gave an overview on
possible risks in terms of a dietary salt reduction,
suggesting that with a modest dietary salt restriction to
56 g/day, short episodes of severe diarrhea or longer
episodes of vomiting are not likely to cause sodium
deciency. Even in geriatric patients and pregnant
women, Klaus et al. [45] deem the benet as exceeding
potential harm. Drastic salt restrictions to 1 g/day are not
recommended due to pathophysiological considerations
[45].
Since the 1980s, the salt industry has tried to promote
the view that salt reduction provides only a negligible
benet [41,51], but now, concerted efforts of relevant
working groups and advisory panels throughout the
world and the WHO are exerting pressure on them to
change their strategy [49,52]. These organizations pub-
lish action plans for the implementation of salt-reducing
strategies and give recommendations for a population-
wide salt intake reduction. For example, the WHO has
set out a worldwide target of less than 5 g/day for adults
[49], or a reduction of salt intake by approximately one
half per day assuming that western people consume
about 10 g sodium daily. Though these measures are
all voluntary and not regulated by law, reduction of
sodium in the diet is increasingly becoming a public
health issue. A coronary heart disease model including
the entire US population has recently indicated that
lowering salt intake in the population would in all like-
lihood reduce cardiovascular disease and deaths, and
lower medical costs [53]. Most of the strategies are based
on the United Kingdom Food Standards Agencys pro-
gramon salt reduction, the Consensus Action on Salt and
Health (CASH) [52]. CASH involves government,
business, and consumer and health groups, based on
the premise that action must address people, environ-
ment, and products. Since CASHwas set up in 1996, with
the stepwise and slow reduction of salt content in
primary processed foods bought in supermarkets, public
health campaigns, and a clear labeling, salt intake has
already fallen as documented by a random sample of the
population [40]. Preexisting strategies can now act as a
model for other initiatives in different countries such as
the less salt for all task force [54], which is currently
being planned in Germany. After the critical assessment
of risks and benets of a general restriction of dietary salt
intake, they want to implement short-term, medium-
term and long-term goals. Short and medium goals are to
concentrate on the improvement of the health status of
the population aiming for sodium labeling of food pro-
ducts and the stepwise reduction of salt in processed
food, in fast food chains and restaurants. For long-term
goals, individual patients should be addressed via sus-
tainable health promotion (e.g. advice for nutritional
behavior changes with the focus of promotion in media,
schools, and other education sites). For hypertensive
patients, structured training courses could be a key,
because such training programs with appropriate infor-
mation on nutrition have been successfully imple-
mented to improve patients understanding of hyper-
tension and associated complications, thus increasing
adherence with nondrug and drug-based treatments
and improving patient-relevant outcomes [5559].
Our overview based on secondary and primary literature
published to date proves a blood pressure-lowering effect
when hypertensive patients reduce their salt intake.
However, no valid information was available to show
826 Journal of Hypertension 2011, Vol 29 No 5
conclusively that salt reduction is benecial or harmful in
terms of patient-relevant outcomes.
Acknowledgements
The authors thank Siw Waffenschmidt (IQWiG) for
assistance with the literature search strategies, Thomas
Werner Gratzer and Ursula Pu ringer for support in data
editing, and Eugenia Lamont for nal editing of the
article.
E.M., K.J., K.H., T.S., N.P., and A.S. are involved as
external experts in the preparation of rapid reports on
the benet assessment of nondrug treatment strategies
in patients with essential hypertension for IQWiG, the
German Institute for Quality and Efciency in Health-
care. L.G.H. is an employee of IQWiG.
References
1 World Health Organization (WHO). The World Health Report 2002:
reducing risks, promoting healthy life; 2002. http://www.who.int/entity/
whr/2002/en/whr02_en.pdf. [Accessed 16 February 2010].
2 Staessen JA, Li Y, Thijs L, Wang JG. Blood pressure reduction and
cardiovascular prevention: an update including the 20032004 secondary
prevention trials. Hypertens Res 2005; 28:385407.
3 Turnbull F. Effects of different blood-pressure-lowering regimens on major
cardiovascular events: results of prospectively-designed overviews of
randomised trials. Lancet 2003; 362:15271535.
4 Frost CD, Law MR, Wald NJ. By how much does dietary salt reduction
lower blood pressure? II: analysis of observational data within populations.
BMJ 1991; 302:815818.
5 Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction
lower blood pressure? III: analysis of data from trials of salt reduction. BMJ
1991; 302:819824.
6 Wannamethee SG, Shaper AG. Patterns of alcohol intake and risk of stroke
in middle-aged British men. Stroke 1996; 27:10331039.
7 Wilson PW, DAgostino RB, Sullivan L, Parise H, Kannel WB. Overweight
and obesity as determinants of cardiovascular risk: the Framingham
experience. Arch Intern Med 2002; 162:18671872.
8 Dickinson HO, Mason JM, Nicolson DJ, Campbell F, Beyer FR, Cook JV, et
al. Lifestyle interventions to reduce raised blood pressure: a systematic
review of randomized controlled trials. J Hypertens 2006; 24:215233.
9 He FJ, MacGregor GA. Effect of longer-term modest salt reduction on
blood pressure. Cochrane Database Syst Rev 2004:CD004937.
10 Ju rgens G, Graudal NA. Effects of low sodium diet versus high sodium diet
on blood pressure, renin, aldosterone, catecholamines, cholesterols, and
triglyceride. Cochrane Database Syst Rev 2004:CD004022.
11 Strazzullo P, DElia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and
cardiovascular disease: meta-analysis of prospective studies. BMJ 2009;
339:b4567.
12 European Society of Hypertension, European Society of Cardiology. 2007
guidelines for the management of arterial hypertension: the Task Force for
the Management of Arterial Hypertension of the European Society of
Hypertension (ESH) and of the European Society of Cardiology (ESC).
J Hypertens 2007; 25:11051187.
13 National Institute for Health and Clinical Excellence (NICE). Essential
hypertension: managing adult patients in primary care. 2004. http://
www.nice.org.uk/nicemedia/pdf/CG18background.pdf. [Accessed 16
February 2010].
14 World Health Organization (WHO). Clinical guidelines for the
management of hypertension; 2005. http://www.emro.who.int/dsaf/
dsa234.pdf. [Accessed 16 February 2010].
15 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr,
et al. The Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7
report. JAMA 2003; 289:25602572.
16 Canadian Hypertension Education Program (CHEP). Recommendations
for the Management of Hypertension. http://hypertension.ca/downloads/
chep/ids/docs/PDF/Complete_Recommendations_2009.pdf. [Accessed
16 February 2010].
17 Institute for Quality and Efciency in Healthcare. General Methods: Version
3.0. http://www.iqwig.de/download/IQWiG_General_methods_V-3-0.pdf.
[Accessed 16 February 2010].
18 Becker LA, Oxman AD. Chapter 22. Overviews of reviews; 2008. http://
www.cochrane-handbook.org/. [Accessed 16 February 2010].
19 Horvath K, Jeitler K, Siering U, Stich AK, Skipka G, Gratzer TW,
Siebenhofer A. Long-term effects of weight-reducing interventions in
hypertensive patients: systematic review and meta-analysis. Arch Intern
Med 2008; 168:571580.
20 Institut fu r Qualita t und Wirtschaftlichkeit im Gesundheitswesen.
Nutzenbewertung nichtmedikamento ser Behandlungsstrategien bei
Patienten mit Bluthochdruck: Gewichtsreduktion; Abschlussbericht.
Version 1.0; A05-21A. https://www.iqwig.de/download/A05-
21A_Abschlussbericht_Gewichtsreduktion_bei_Bluthochdruck_neu.pdf.
[Accessed 9 October 2009].
21 Siebenhofer A, Horvath K, Jeitler K, Berghold A, Stich AK, Matyas E, et al.
Long-term effects of weight-reducing drugs in hypertensive patients.
Cochrane Database Syst Rev 2009:CD007654.
22 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP,
et al. The PRISMA statement for reporting systematic reviews and
meta-analyses of studies that evaluate healthcare interventions: explanation
and elaboration. BMJ 2009; 339:b2700.
23 Institut fu r Qualita t und Wirtschaftlichkeit im Gesundheitswesen.
Nutzenbewertung nichtmedikamento ser Behandlungsstrategien bei
Patienten mit essenzieller Hypertonie: Kochsalzreduktion; Rapid
Report. Version 1.0; A05-21B. http://www.iqwig.de/download/
A05-21B_Rapid_Report_Nichtmedikamentoese_Behandlungsstrategien_
bei_Hypertonie_Kochsalzreduktion.pdf. [Accessed 16 February 2010].
24 Oxman AD, Guyatt GH. Validation of an index of the quality of review
articles. J Clin Epidemiol 1991; 44:12711278.
25 Oxman AD, Guyatt GH, Singer J, Goldsmith CH, Hutchison BG, Milner RA,
Streiner DL. Agreement among reviewers of review articles. J Clin
Epidemiol 1991; 44:9198.
26 He FJ, MacGregor GA. Effect of modest salt reduction on blood pressure: a
meta-analysis of randomized trials. Implications for public health [see
comment]. J Hum Hypertens 2002; 16:761770.
27 He FJ, MacGregor GA. How far should salt intake be reduced?
Hypertension 2003; 42:10931099.
28 Hooper L, Bartlett C, Davey SG, Ebrahim S. Advice to reduce dietary salt
for prevention of cardiovascular disease [update of Cochrane Database
Syst Rev 2003:CD003656; PMID: 12917977]. Cochrane Database Syst
Rev 2004:CD003656.
29 Hooper L, Bartlett C, Davey Smith G, EbrahimS. Systematic review of long
term effects of advice to reduce dietary salt in adults [see comment]. BMJ
2002; 325:628.
30 Morgan T, Adam W, Gillies A, Wilson M, Morgan G, Carney S.
Hypertension treated by salt restriction. Lancet 1978; 1:227
230.
31 Alli C, Avanzini F, Bettelli G, Bonati M, Colombo F, Corso R, et al. Feasibility
of a long-term low-sodium diet in mild hypertension. J Hum Hypertens
1992; 6:281286.
32 Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger WH Jr,
Kostis JB, et al. Sodium reduction and weight loss in the treatment of
hypertension in older persons: a randomized controlled trial of
Nonpharmacologic Interventions in the Elderly (TONE). TONE
Collaborative Research Group. JAMA 1998; 279:839846.
33 Appel LJ, Espeland MA, Easter L, Wilson AC, Folmar S, Lacy CR. Effects of
reduced sodium intake on hypertension control in older individuals: results
from the Trial of Nonpharmacologic Interventions in the Elderly (TONE).
Arch Intern Med 2001; 161:685693.
34 Thaler BI, Paulin JM, Phelan EL, Simpson FO. A pilot study to test the
feasibility of salt restriction in a community. N Z Med J 1982; 95:839
842.
35 Morgan TO, Adams WR, Hodgson M, Gibberd RW. Failure of therapy to
improve prognosis in elderly males with hypertension. Med J Aust 1980;
2:2731.
36 Morgan T, Anderson A. Sodium restriction can delay the return of
hypertension in patients previously well controlled on drug therapy. Can J
Physiol Pharmacol 1987; 65:17521755.
37 Arroll B, Beaglehole R. Salt restriction and physical activity in treated
hypertensives. N Z Med J 1995; 108:266268.
38 He FJ, Marciniak M, Visagie E, Markandu ND, Anand V, Dalton RN,
MacGregor GA. Effect of modest salt reduction on blood pressure, urinary
albumin, and pulse wave velocity in white, black, and Asian mild
hypertensives. Hypertension 2009; 54:482488.
39 Meland E, Aamland A. Salt restriction among hypertensive patients: modest
blood pressure effect and no adverse effects. Scand J Prim Healthcare
2009; 27:97103.
40 He FJ, MacGregor GA. A comprehensive review on salt and health and
current experience of worldwide salt reduction programmes. J Hum
Hypertens 2009; 23:363384.
Benefit assessment of salt reduction in hypertension Matyas et al. 827
41 He FJ, MacGregor GA. A comprehensive review on salt and health and
current experience of worldwide salt reduction programmes. J Hum
Hypertens 2009; 23:363384.
42 Khaw KT, Bingham S, Welch A, Luben R, OBrien E, Wareham N, Day N.
Blood pressure and urinary sodium in men and women: the Norfolk Cohort
of the European Prospective Investigation into Cancer (EPIC-Norfolk). Am
J Clin Nutr 2004; 80:13971403.
43 Intersalt Cooperative Research Group. Intersalt: an international study of
electrolyte excretion and blood pressure. Results for 24 h urinary sodium
and potassium excretion. Intersalt Cooperative Research Group. BMJ
1988; 297:319328.
44 Elliott P, Stamler J, Nichols R, Dyer AR, Stamler R, Kesteloot H, Marmot M.
Intersalt revisited: further analyses of 24 h sodium excretion and blood
pressure within and across populations. Intersalt Cooperative Research
Group. BMJ 1996; 312:12491253.
45 Klaus D, Hoyer J, Middeke M. Salt restriction for the prevention of
cardiovascular disease. Dtsch Arztebl Int 2010; 107:457462.
46 Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al.
Effects on blood pressure of reduced dietary sodium and the Dietary
Approaches to Stop Hypertension (DASH) diet. DASH-Sodium
Collaborative Research Group. N Engl J Med 2001; 344:310.
47 Blumenthal JA, Babyak MA, Hinderliter A, Watkins LL, Craighead L, Lin PH,
et al. Effects of the DASH diet alone and in combination with exercise and
weight loss on blood pressure and cardiovascular biomarkers in men and
women with high blood pressure: the ENCORE study. Arch Intern Med
2010; 170:126135.
48 Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK,
et al. Long term effects of dietary sodium reduction on cardiovascular
disease outcomes: observational follow-up of the trials of hypertension
prevention (TOHP). BMJ 2007; 334:885888.
49 World Health Organization (WHO). Reducing salt intake in populations;
2007. http://www.who.int/dietphysicalactivity/reducingsaltintake_EN.pdf.
[Accessed 16 February 2010].
50 Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson
B, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after
bariatric surgery. N Engl J Med 2004; 351:26832693.
51 Godlee F. The food industry ghts for salt. BMJ 1996; 312:12391240.
52 Consensus Action on Salt and Health (CASH). http://
www.actiononsalt.org.uk/. [Accessed 10 November 2010].
53 Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM,
Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on
future cardiovascular disease. N Engl J Med 2010; 362:590599.
54 Klaus S, Middeke L, Hoyer H. An appeal to start a Task Force Lower salt
intake for everybody [in German]. Dtsch Med Wochenschr 2008;
133:13171319.
55 The ALLHAT Ofcers and Coordinators for the ALLHAT Collaborative
Research Group. Major outcomes in high-risk hypertensive patients
randomized to angiotensin-converting enzyme inhibitor or calcium channel
blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288:29812997.
56 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr,
et al. Seventh report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure.
Hypertension 2003; 42:12061252.
57 Psaty BM, Manolio TA, Smith NL, Heckbert SR, Gottdiener JS, Burke GL,
et al. Time trends in high blood pressure control and the use of
antihypertensive medications in older adults: the Cardiovascular Health
study. Arch Intern Med 2002; 162:23252332.
58 Fahey T, Schroeder K, Ebrahim S. Educational and organisational
interventions used to improve the management of hypertension in primary
care: a systematic review. Br J Gen Pract 2005; 55:875882.
59 Trocha AK, Schmidtke C, Didjurgeit U, Muhlhauser I, Bender R, Berger M,
Sawicki PT. Effects of intensied antihypertensive treatment in diabetic
nephropathy: mortality and morbidity results of a prospective controlled
10-year study. J Hypertens 1999; 17:14971503.
828 Journal of Hypertension 2011, Vol 29 No 5