The Effects of a Community-Based Sodium Reduction Program in Rural China – A Cluster-Randomized Trial
The Effects of a Community-Based Sodium Reduction Program in Rural China ± A Cluster- Randomized Trial
Nicole Li 0 1
Lijing L. Yan 0 1
Wenyi Niu 0
Chen Yao 0
Xiangxian Feng 0
Jianxin Zhang 0
Jingpu Shi 0
Yuhong Zhang 0
Ruijuan Zhang 0
Zhixin Hao 0 1
Hongling Chu 0 1
Jing Zhang 0 1
Xian Li 0 1
Jianhong Pan 0
Zhifang Li 0
Jixin Sun 0
Bo Zhou 0
Yi Zhao 0
Yan Yu 0
Michael Engelgau 0
Darwin Labarthe 0
Jixiang Ma 0
Stephen MacMahon 0
Paul Elliott 0
Yangfeng Wu 0 1
Bruce Neal 0
0 Editor: C. Mary Schooling, Hunter College , UNITED STATES
1 0 Ningxia Medical University , Yinchuan, Ningxia , China , 11 Xi'an Jiaotong University , Xi'an, Shaanxi , China , 12 United States Centers for Disease Control and Prevention , Beijing , China , 13 Chinese Center for Disease Control and Prevention , Beijing , China , 14 Imperial College London, United Kingdom, 15 Royal Prince Alfred Hospital , Sydney
salt consumption in rural northern China.
This study was a cluster-randomized trial done over 18 months in 120 townships (one village
from each township) from five provinces. Sixty control villages were compared to 60
intervention villages that were given access to a reduced-sodium, added-potassium salt
substitute in conjunction with a community-based health education program focusing on sodium
reduction. The primary outcome was the difference in 24-hour urinary sodium excretion
between randomized groups.
Data Availability Statement: We have confirmed
with our major funding agency National Heart,
Lung and Blood Institute in The United States in
July this year, that the study dataset will be made
available upon request from September 2016
onwards through the NIH data
repositoryBioLINCC. The website address is: https://biolincc.
Funding: This project has been funded in part with
Federal funds from the National Heart, Lung, and
Blood Institute, National Institutes of Health,
Department of Health and Human Services, and
National Center for Chronic Disease Prevention and
Health Promotion (CDC), under Contract No.
HHSN268200900027C. Additional support has
been received from the UnitedHealth Group
Chronic Disease Initiative. Bruce Neal is supported
by an Australian Research Council Future
Fellowship and National Health and Medical
Research Council Senior Research Fellowship and
Nicole Li by an Australian National Health and
Medical Research Council Overseas Fellowship.
Paul Elliott is supported through the MRC-PHE
Centre for Environment and Health, Imperial
College London, and by the National Institute for
Health Research (NIHR) Biomedical Research
Centre at Imperial College Healthcare NHS Trust
and Imperial College London; he is an NIHR Senior
Investigator. The views expressed are those of the
authors and not necessarily those of any sponsors.
Competing Interests: Bruce Neal is the Chair of
Australian Division of World Action on Salt and
Health. This does not alter our adherence to PLOS
ONE policies on sharing data and materials.
Among 1,903 people with valid 24-hour urine collections, mean urinary sodium excretion in
intervention compared with control villages was reduced by 5.5% (-14mmol/day, 95%
confidence interval -26 to -1; p = 0.03), potassium excretion was increased by 16% (+7mmol/
day, +4 to +10; p<0.001), and sodium to potassium ratio declined by 15% (-0.9, -1.2 to -0.5;
p<0.001). Mean blood pressure differences were -1.1 mm Hg systolic (-3.3 to +1.1; p = 0.33)
and -0.7 mm Hg diastolic (-2.2 to +0.8, p = 0.35) and the difference in the proportion with
hypertension was -1.3% (-5.1 to 2.5, p = 0.56).
There were clear differences in population sodium and potassium intake between villages that were most likely a consequence of increased use of salt substitute. The absence of effects on blood pressure reflects the moderate changes in sodium and potassium intake achieved.
Clinicaltrials.gov identifier: NCT01259700.
Stroke is the leading cause of death in China, responsible for about 1.7 million deaths each
]. Excess sodium intake is a key determinant of high blood pressure , the leading
cause of stroke [
]. The magnitude of the effect of sodium on blood pressure is such that each
75mmol difference in daily salt intake translates into an approximate 5.4mmHg difference in
systolic blood pressure amongst individuals with hypertension and 2.4mmHg amongst
individuals with non-hypertensive starting levels of blood pressure[
]. China, especially in the
rural areas, has one of the highest sodium intake levels in the world [
]. In western
populations most dietary sodium derives from processed and restaurant foods but in rural China the
majority comes from salt added in cooking and condiments at home . In this situation, the
substitution of salt with an alternate product lower in sodium may provide a particular
opportunity to deliver a large public health benefit at low cost [
]. Beneficial effects of salt
substitution on urinary electrolytes and blood pressure have been achieved in randomised trials done
in selected populations including those in rural China [9±14] but whether effects can be
achieved in the general community is unknown. We therefore undertook a trial of a pragmatic
intervention using a reduced-sodium, added-potassium salt substitute to determine whether
this could reduce average population sodium intake in rural China.
Subjects and Methods
Details of the rationale and design of the China Rural Health Initiative Sodium Reduction
Study have been described previously [
]. In brief, the sodium reduction study is one of the
two parallel cluster-randomized controlled trial of the China Rural Health Initiative Project
conducted in northern rural China between May 2011 and November 2012. It was done in
collaboration with local academic institutions and governments in Hebei, Liaoning, Shanxi and
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Shaanxi provinces and the Ningxia Autonomous Region. The China Rural Health Initiative
was registered with clinicaltrial.gov (NCT01259700). The study design is summarized in Fig 1.
The project was reviewed and approved by the Institutional Review Boards of the Peking
University Health Science Center in Beijing, China and of the Duke University Health System in
Durham, USA. We have obtained verbal group consent from the chief of each of the study
villages to implement the study intervention and obtained written consent from all individuals
who participated in the end of the study survey. Verbal group consent from the village chiefs
have been approved by the above mentioned ethics committees.
Provinces, townships and villages included
Two counties were selected from each province/autonomous region and 12 townships from
each county, making a total of 120 townships. Within each township one village was selected
for participation. The risk of contamination between adjacent intervention and control villages
was minimized by the organizational separation of the townships and a geographic separation
of 10 kilometers or more between participating villages. A typical township in the study
comprised about 17 villages and included 25,000 people with at least one village doctor providing
basic health services in each village. The average population size of included villages was 1,867
individuals living in 512 households with an annual per capita income of US$884.
Townships were randomized in a 1:1 ratio to either the sodium reduction program or
continued usual practices with stratification by county. Intervention villages were then further
assigned at random to receive subsidization of the price of salt substitute, or not, using the
same approach to stratification.
Intervention and control
Intervention villagesÐthe salt reduction program comprised community-based health
education and availability of reduced-sodium, added-potassium salt substitute at village shops. The
health education component was delivered by the township health educators with assistance
from the village council and the village doctors through public lectures, the display and
distribution of promotional materials, and special interactive education sessions targeted towards
individuals at elevated risk of vascular diseases [
]. The salt substitute was made available for
purchase in all intervention villages and promoted through the health education component of
the intervention. Residents in villages randomized to the price subsidy were provided with
coupons that enabled the purchase of salt substitute at the same price as usual salt. Control
villages—continued their usual practices and were exposed to little by way of efforts to achieve
individual or population-wide salt reduction.
A population survey was done at the end of the intervention period amongst an age- and
sexstratified random sample of 20 or more consenting adults drawn from each of 119 villages,
resulting in 2,566 survey participants. One village in the control group was lost to follow-up
with the site urbanized and the villagers relocated. The survey included a brief
intervieweradministered questionnaire, measurement of blood pressure, height and weight, and the
collection of a 24-hour urine sample. Blood pressure was measured in duplicate with the
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Fig 1. Study CONSORT Flow Diagram.
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participant seated after 5 minutes rest, using an automated electronic sphygmomanometer
(Omron Intellisense HEM 7301 IT) with measurements made at least two minutes apart.
Materials and instructions for collecting a timed 24-hour urine sample were provided. On the
day of collection, participants were asked to urinate and discard that sample, and then collect
all urine in the following 24 hours. At the same time the next day they were asked to urinate
and collect that void before completing the 24 hour urine collection. The samples were
collected, the volume was recorded, and an aliquot was shipped to a central lab for assay of
sodium, potassium, and creatinine.9 Individuals that were pregnant, breastfeeding,
menstruating, vomiting, had diarrhea, excessive sweating, or symptoms of a urinary tract infection did
not provide a urine collection. Urine samples were excluded if participants reported missing
the first morning void, missing more than one void, a collection period less than 22 hours or
longer than 26 hours, or spilling more than 10% of the total volume. Samples contaminated
with faeces were also excluded as were collections that had a volume of less than 500mL or
greater than 6000mL, or a 24-hour creatinine excretion of less than 4mmol or greater than
25mmol in women and less than 6mmol or greater than 30mmol in men [16±19].
For each individual, the 24-hour sodium excretion value (mmol/day) was calculated as the
concentration of sodium in the urine (mmol/L) multiplied by the urinary volume (L/day). The
conversion from sodium (Na) to salt (NaCl) was made by multiplying the sodium value in
mmol by 23 to obtain the sodium value in milligrams and then multiplying that figure by 2.54
to obtain the value for salt (NaCl) in milligrams.
The primary outcome was 24-hour urinary sodium excretion measured as a proxy for salt
intake. The secondary outcomes were 24-hour urinary potassium excretion, urinary sodium to
potassium ratio, systolic blood pressure, diastolic blood pressure, and the proportion with
hypertension (defined as a measured systolic blood pressure of 140mmHg or above, a
measured diastolic blood pressure of 90mmHg or above, or the use of blood pressure lowering
therapy in the last two weeks). A series of process outcomes measuring knowledge and
behaviors relating to salt and salt substitute were also recorded as were spontaneously reported
The study was designed to provide at least 90% power (with a two-sided alpha = 0.05) to detect
a difference in mean 24-hour excretion of sodium of at least 11mmol/day (0.65g/day salt)
between intervention and control clusters. This estimate assumed a standard deviation of
24-hour sodium excretion of 60mmol/day (observed in study 95mmol/day), an intra-cluster
correlation coefficient of 0.05 (observed in study 0.07), and a sample of 2,400 individuals
drawn from 120 clusters randomized equally between intervention and control.
Statistical analyses were done using the SAS system version 9.2 (Chinese simplified).
Analysis of treatment effects was by intention to treat with between group comparisons for
the study outcomes made using generalized estimating equations (GEE) with clusters
accounted for as random effects for continuous outcomes and using GEE logistic regression
model with clusters accounted for as fixed effects for categorical outcomes. All statistical
analyses were adjusted for the effects of clustering and additional adjustment were not done. Where
data were missing, the number of observation was reported and missing values were not
imputed. A derived variable was considered missing (for example, 24 hour urinary sodium
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excretion) when one or more of the related variables was missing (urinary sodium
concentration and/or 24 hour urine volume). Generalized estimating equations (GEE) accounting for
clustering effects were used to obtain effect estimates, 95% confidence intervals, and p-values
for all outcomes. The primary comparison was between intervention clusters (n = 60) and
control clusters (n = 59) with outcome data. In addition, the effects of subsidizing the price of
the salt substitute were explored by estimating effects in the intervention clusters with price
subsidy (n = 30) vs. those without price subsidy (n = 30). Finally, analyses were repeated in
participant subgroups defined by median age (58 years), sex, years of education, median BMI
(24kg/m2), smoking status, and alcohol consumption. A p-value of less than 0.05 was
considered significant for the primary comparison but results for secondary analyses and tests of
interaction were interpreted in light of the multiple comparisons made.
The mean age of the 2,566 survey participants was 55 years, 50% were female, and one third
smoked (Table 1). Survey participants provided 1,903 eligible urine samples (975 from
intervention villages and 928 from control villages) with 663 samples missing entirely or deemed
ineligible for another reason. The main reasons for ineligible samples were failure to collect all
urine voids (321 individuals) and reported spillage (93 individuals) (Fig 1). There were no
differences in the reasons for missing samples between intervention and control villages.
Individuals with missing urine samples were noted to have on average lower levels of BMI (23.8 vs.
24.5kg/m2; p<0.001) but there were no differences in age and gender.
Among the 1,903 people with eligible 24-hour urine collections, mean urinary sodium
excretion in intervention compared with control villages was 5.5% lower (-14mmol/day, 95%
confidence interval -26 to -1; p = 0.03), potassium excretion was 16% higher (+7mmol/day, +4
to +10; p<0.001), and sodium to potassium ratio 15% lower (-0.9, -1.2 to -0.5; p<0.001)
(Table 2). The results were similar if analyses were done including urines from 468 additional
individuals with urine samples that were not entirely missing but deemed ineligible for the
primary analyses (ST1). Mean blood pressure differences were -1.1 mm Hg systolic (-3.3 to +1.1;
p = 0.33), -0.7 mm Hg diastolic (-2.2 to +0.8 p = 0.35), and percentage with hypertension
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*Numbers reported after ± are standard deviations unless otherwise stated
&Hypertension de®ned as having systolic blood pressure at or above 140 mm Hg and/or a diastolic blood pressure at or above 90 mm Hg and/or reports use
of blood pressure lowering medication in the last two weeks.
3% lower (-5.1 to 2.5%, p = 0.56) (Table 2). There was no heterogeneity of effects of
intervention versus control on sodium excretion in the subgroups studied (all p>0.4).
There was a numerically, but not statistically significant, greater effect of the intervention
on the primary outcome with subsidization of the price of salt substitute (p = 0.20) (Table 3).
The same was true for all the secondary outcomes (all p>0.06) and the findings were again
comparable if analyses included individuals with urine specimens collected but deemed
ineligible on the basis of the pre-specified urine inclusion criteria (ST 2).
There was greater knowledge about the adverse effects of salt, the harm caused by high
blood pressure, concern about the levels of salt in the diet, and the recommended upper limit
for daily salt consumption in intervention compared to control villages (all p<0.001)
(Table 2). Use of salt substitute was ten-fold higher in the intervention villages and among
these villages, the reported use of salt substitute was double in the villages with the price
subsidy compared to the villages without the price subsidy (Table 3).
The most commonly reported adverse events occurring during the study period were
dizziness, headache, weakness, stomach ache, hypotension, and fall which occurred at similar rates
in the two randomised groups (all p>0.41). Serious vascular events were reported by few of
those surveyed with no significant differences between randomised groups for stroke,
coronary heart disease, heart failure, kidney disease or hyperkalaemia (all p>0.15).
The salt reduction program achieved the intended lower urinary sodium excretion with a
reduction of about three quarters of a gram of salt per day against a background daily
consumption of approximately fourteen grams. The increase in urinary potassium, fall in the
urinary sodium to potassium ratio, and ten-fold higher reported use of salt substitute among
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*Mean ± standard deviations unless otherwise stated.
&Hypertension de®ned as having systolic blood pressure at or above 140 mm Hg and/or a diastolic blood pressure at or above 90 mm Hg and/or reports use
of blood pressure lowering medication in the last two weeks.
intervention compared to control villages, suggest that the fall in urinary sodium consumption
was achieved primarily through use of salt substitute. Effects on blood pressure were modest
and non-significant but consistent in magnitude with the fall in sodium reduction achieved. A
larger study would be required to reliably detect any effect on blood pressure of the observed
changes in sodium consumption.
Salt substitute costs about twice as much as usual salt (4CNY [US$0.65] vs. 2CNY [US
$0.33] per kg). While salt substitute is still a low cost condiment, we anticipated that this
would be a disincentive to use. Accordingly, we investigated the effect of price subsidy and
found the uptake of salt substitute in villages with a subsidy to be almost twice that of villages
with no price subsidy. If the price differential could be removed, or salt substitute could in
some other way replace usual salt as the staple commodity, then average population sodium
consumption could likely be reduced by considerably more than the 5.5% reduction achieved
in this trial. A larger sodium reduction, in conjunction with a rise in potassium, would be
expected to translate into major public health benefits resulting from reductions in blood
pressure levels, the incidence of stroke, and other blood pressure-related diseases [
]. Given that
effects of salt substitutes are larger amongst individuals with higher baseline blood pressure
levels the magnitude of protection would be expected to be greater amongst hypertensives.
The trial has a number of strengths. It was carried out in a rural setting in China where
most sodium in the diet is from cooking or condiment use and where salt substitute has the
greatest potential to reduce sodium intake [
]. The trial benefitted from its large size and
robust randomized design, and included gold standard assessment of dietary sodium
consumption using 24-hour urine collections. The exclusion of individuals with suspected
inaccurate or incomplete 24hr urine samples maximized the precision of the estimates in each group
and our capacity to detect changes. It was, however, an open rather than a blinded study and
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to avoid bias considerable efforts were required to ensure that the population surveys were
done identically in intervention and control villages [
]. The study was powered to detect
effects on urinary markers of sodium and potassium consumption but was not designed to
detect effects on blood pressure and hypertension which were specified only as secondary
outcomes. While the intended sample size was not achieved the study still had reasonable power
to detect the primary effect under investigation. Baseline survey data were not available
because of resource constraints. Although an assessment based upon follow-up surveys alone
was an entirely valid approach to evaluation of the intervention, the lack of baseline data
reduced the statistical power and made the treatment effect comparison between two
treatment groups less robust. It is also possible that there were chance baseline imbalances between
groups that this design would not have controlled for. Antihypertensive drug use can influence
urinary electrolyte excretion but seems unlikely to have substantively influenced trial results
given the comparable rates of usage in each randomised group. Salt substitutes have been
available in multiple markets around the world including China for many years and are considered
safe and well-tolerated.[21±24] Accordingly we did not systematically collect tolerability data
during this study and advised use in the intervention communities according to established
practices in China.
There are eight randomized trials of salt substitute published to date with six reporting
significant falls in systolic blood pressure [9±14] and the remainder trends toward blood pressure
]. These trials all provided salt substitute to intervention participants at
no cost and showed much larger reductions in sodium excretion and blood pressure than were
achieved with the strategy used in the present study. Our study demonstrates that a
low-intensity community-based sodium reduction strategy can lower average sodium intake but also
highlights the rather limited impact that can be achieved by this approach. The full potential of
salt substitution in rural China will only be delivered by a policy that makes salt substitute the
standard condiment for the entire population. Were this polity to be promoted throughout
rural China, it should result in a population wide decline in blood pressure and the prevention
of many tens of thousands of strokes and heart attacks each year. [
Population sodium intake was reduced by our intervention, primarily through increased use
of salt substitute. Larger effects could be achieved in rural China by a wholesale switch from
salt to salt substitute, with the potential for major public health benefit in this population
which is at very high risk of stroke.
S1 Table. Supplementary Table 1. Estimated effects of sodium reduction strategy for 60
intervention compared to 59 control villages on urinary outcomes (with all urine samples)
S2 Table. Supplementary Table 2. Estimated effects of sodium reduction strategy for 30
intervention villages with price subsidy for salt substitute compared to 30 intervention villages
without price subsidy for salt substitute on urinary outcomes (with all urine samples)
S1 File. Final Follow Up Survey Questionnaire Chinese version (original).
S2 File. Final Follow Up Survey Questionnaire English version (translated).
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S3 File. China Rural Health Initiative Protocol Chinese version (original).
S4 File. China Rural Health Initiative Protocol English version (translated).
S5 File. CONSORT Checklist.
The Steering Committee for the China Rural Health Initiative is comprised of: Qide Han
(Honorary Chair), Yang Ke (Chair), Yangfeng Wu (Vice Chair and Secretary General),
Michael Merson (Vice Chair), Bruce Neal (Vice Chair), Paul Elliott, Xiangxian Feng, Stephen
Leeder, Lingzhi Kong, Alan Lopez, Qun'an Mao, Jingpu Shi, Jianxin Zhang, Ruijuan Zhang
and Yuhong Zhang. The Scientific Committee for the Sodium Reduction Study is comprised
of Bruce Neal (Chair), Lijing L. Yan (Vice Chair), Elizabeth DeLong, Michael Dibley, Jixiang
Ma, Wenyi Niu, Yangfeng Wu. Ad hoc members of the Scientific Committee are Darwin
Labarthe and Paul Elliott.
We would like to thank the supports from the national, provincial, county, township, and
village governments and health authorities and cooperation of our study participants. We
would also like to thank the county leaders (Zhongbao Ji, Xintai Liu, Jianwei Liang, Shusheng
Liu, Wenli Wang, Fangjie Liu, Hongyi Su, Lei Pan, Xuanmin Yang, Xiaowei Xing), county
health educators (Jianhua Zhang, Wangui Qi, Haigen Li, Jianghai Yao, Jing Liu, Lizhong Wu,
Kefeng Cai, Hongyi Su, Xiujuan Tian, Shuai Huang, Weiping Zhu), county project officers
(Xinchun He, Min Wang, Yunfeng Bai, Junhui Ren, Hui Li, Yan Yuan, Xiaobing Liu, Yuxia
Ma, Zhonggang Zhao, Mingliang Ren, Xin Mao), and project coordination center team
members (Yanqing Wang, Xuejun Yin, Cong Li, Maoyi Tian) for their contributions to our study.
Conceptualization: YW BN.
Formal analysis: XL JP.
Funding acquisition: YW.
Investigation: YW BN LY NL WN ME DL JM SM PE XF Jianxin Zhang J. Shi Y. Zhang RZ.
Methodology: YW BN LY NL WN ME DL JM SM PE.
Project administration: ZH HC Jing Zhang ZL J. Sun BZ Y. Zhao YY.
Resources: XF Jianxin Zhang J. Shi Y. Zhang RZ.
Writing ± original draft: NL LY.
Writing ± review & editing: NL LY YW BN PE.
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