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Clinical and Experimental Hypertension

ISSN: 1064-1963 (Print) 1525-6006 (Online) Journal homepage: http://www.tandfonline.com/loi/iceh20

Effects of salt substitute on home blood pressure


differs according to age and degree of blood
pressure in hypertensive patients and their
families

Jihong Hu, Liancheng Zhao, Brian Thompson, Yawei Zhang & Yangfeng Wu

To cite this article: Jihong Hu, Liancheng Zhao, Brian Thompson, Yawei Zhang & Yangfeng Wu
(2018): Effects of salt substitute on home blood pressure differs according to age and degree of
blood pressure in hypertensive patients and their families, Clinical and Experimental Hypertension,
DOI: 10.1080/10641963.2018.1425415

To link to this article: https://doi.org/10.1080/10641963.2018.1425415

Published online: 05 Feb 2018.

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CLINICAL AND EXPERIMENTAL HYPERTENSION
https://doi.org/10.1080/10641963.2018.1425415

Effects of salt substitute on home blood pressure differs according to age and
degree of blood pressure in hypertensive patients and their families
Jihong Hua,c, Liancheng Zhaoa, Brian Thompsond, Yawei Zhangd,e, and Yangfeng Wua,b
a
Department of Epidemiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China; bDepartment of Epidemiology, Public Health School, Peking University Health Science Center, Beijing, China; cPublic Health
School, Gansu University of Chinese Medicine, Gansu, China; dDepartment of Environmental Health Sciences, Yale University School of Public
Health, New Haven, CT, USA; eDepartment of Surgery, Yale University School of Medicine, New Haven, CT, USA

ABSTRACT ARTICLE HISTORY


Background: It is known that home blood pressure (HBP) is a more reliable assessment of hypertension Received 2 August 2017
treatments than clinical blood pressure (BP). Despite this, HBP response to a salt substitute has only Revised 20 October 2017
been evaluated by one study which, did not look at the salt substitute’s effect on family members and Accepted 19 December 2017
did not analyze by age, gender, or BP degree. The aim of this current study was to assess the effects of a KEYWORDS
low-sodium and high-potassium salt substitute on HBP among hypertensive patients and their family Salt substitute; family
members. Methods: A total of 220 households (including 220 hypertensive patients and 380 their members; home blood
families) were randomly assigned to the regular salt or salt substitute groups. HBP was measured at pressure; sodiumpotassium
the beginning, 3rd, 6th, and 12th months. Among the patients (n = 220), only home systolic blood
pressure (HSBP) was significantly reduced, by an adjusted baseline BP of 4.2 mm Hg (95% CI: 1.3–7.0 mm
Hg), in the salt substitute group compared with those in the regular salt group at each visit (all P < 0.05).
There were no detectable differences between groups for home diastolic blood pressure (HDBP) at any
visit. Among the family members, HSBP and HDBP were not significantly different between the groups.
Furthermore, Individuals ≥60 years old, hypertensive patients with stage-2 hypertension, family mem-
bers with hypertension, and women experienced greater HSBP reduction. Conclusions: Older subjects,
those with higher blood pressure, and women experienced greater home blood pressure reduction from
the salt substitute compared to regular salt.

Introduction (DBP) among hypertensive patients (7). However, home


blood pressure (BP) measurement was found to be a more
Hypertension remains the most common cardiovascular risk
reliable assessment of pharmacological and nonpharmacolo-
factor in developing countries, yet most patients have no
gical treatments for hypertension because it has better repro-
access to pharmacological therapy (1). The World Health
ducibility (8) and accuracy, due to the lack of the white coat
Organization has proposed that a 30% reduction in salt/
(9) and placebo effects (10) when compared to clinical BP
sodium intake may reduce the risk of hypertension (2). To
measurement. Until now, only one study in hypertensive
this end, the Center for Disease Control and Prevention
patients has reported that a salt substitute reduced home
recently released dietary sodium guidelines, for 2015–2020,
SBP, while no reduction was observed for home DBP (11).
recommending that no more than 2,300 mg of sodium be
Although Chinese dietary habits are changing (4), about 90%
consumed daily (3). Despite these recommendations, Chinese
of the salt intake still comes from home-cooked foods (12)
and American salt and sodium intakes have remained high, at
and most families still eat at home together. A recent exten-
9.1 g per day and 3330 mg per day, despite dietary shifts in
sive meta-analysis suggested that lowering BP in individuals,
recent years (4,5). In the International Population Study on
irrespective of starting blood pressure, has positive health
Macronutrients and Blood Pressure, only 41.6% of Japanese
benefits (13). Thus, salt substitutes could benefit both patients
participants achieved the target of <10 g/day of salt during
with hypertension and their family members. Despite this
salt-restriction (6). This investigation highlights the difficulty
potential benefit, the home BP response to a salt substitute
of attaining and maintaining long-term voluntary salt control
in family members has not been well examined.
and indicates the need for alternative approaches with equiva-
Sex, age, and degree of hypertension have all been shown
lent effects. Thus, a salt substitute with a low sodium content
to impact sensitivity to a low-sodium intervention (5,14) To
and an acceptable salty flavor would be an ideal population-
our knowledge, only one previous study has investigated a
wide preventative strategy.
subgroup effect of salt substitute on clinical BP (15). This
A recent meta-analysis found that salt substitutes with low
study demonstrated that middle aged people, 40–70 years
sodium and high potassium were effective in lowering clinical
old, had the strongest beneficial clinical BP response
systolic blood pressure (SBP) and diastolic blood pressure

CONTACT Yangfeng Wu wuyf@bjmu.edu.cn Peking University School of Public Health No. 38, Xueyuanlu, Haidian District, Beijing 100083.
Supplemental data for this article can be accessed here.
© 2018 Taylor & Francis
2 J. HU ET AL.

compared with those aged <40 or >70 years (15). Therefore, Industrial Company in accordance with Chinese
an investigation into the subgroup effects of a salt substitute Manufacturing Standards. Salt for both groups had identical
on home BP by age, gender and BP degree is warranted. appearances in 1 kg bags with a code corresponding to the
In this present study, we examined home BP response to a randomization number and was provided free of charge.
salt substitute by age, baseline BP and gender subgroup Participants were strictly instructed to avoid changing their
among 220 households including 220 hypertensive patients ordinary dietary habits and lifestyle and to replace normal salt
and 380 families aged 18 years or older who participated in with the trial salt in all cooking, pickling, and other household
the China Salt Substitute Study-a randomized double–blind uses. Treatment allocation was blinded to the study investi-
controlled trial. gator, participants, and center physicians until the study data-
base was unlocked.

Materials and methods


Home self blood pressure measurements (HSBPM)
Study population
Home Self Blood Pressure Measurements (HSBPM) were
Because the prevalence of hypertension, blood pressure levels, tested at the beginning, 3rd, 6th, and 12th months by patients
and salt intake are more likely to be elevated in Northern with hypertension who had received individual guidance on
China (16) and people hardly eat out of the home in rural how to perform HSBPM correctly with an automatic electro-
areas, this study was conducted in the northern rural China. nic device HEM752 at enrollment (19) (Omron Healthcare
People in northern rural China usually consume 260 mmol/ Co. Ltd, Japan). This device is based on the cuff-oscillometric
day or more of sodium and this study population is consistent method and can store collected data. It was calibrated by
with our previous reports (11,17). Study subjects were study center investigators before each visit. A cuff with a
recruited from either general-practitioner referrals or volun- bladder width of 13cm was used for individuals with an arm
teers at two sites in Beijing during September of 2005. Men circumference of 35 cm or less and a cuff with a bladder width
and women with a SBP above 140 mm Hg or a DBP over of 15 cm was used for individuals with an arm circumference
90 mm Hg were invited by letter or telephone for a re- of more than 35 cm. Hypertensive patients and family mem-
measurement of BP. To be eligible for the trial, patients with bers were asked to take repeated self-measurements of BP
mild to moderate hypertension had to have a clinical SBP three times daily at home, in the early morning (06:00–09:00
above 140 mm Hg or DBP above 90 mm Hg at two measure- hrs), at noon (12:00–14:00 hrs) and in the evening (18:00–
ments. In addition, all patients with hypertension and their 21:00 hrs) on three consecutive days at each follow-up time
family members aged ≥18 years had to agree to replace at least point. The maximum number of BP readings obtained per
half of their dietary salt with the salt-substitute under study. person per visit was 18.
Patients and their families were required to have no clear Subjects with less than 12 BP readings at every visit were
established indication for or contra-indication to the use of invalid and excluded from the study analysis. The percentage
the study’s salt substitute, such as the use of a potassium- of valid home BP among family members in the salt substitute
sparing medication or significant renal impairment (serum group at every visit (including beginning, 3rd, 6th, and 12th
creatinine >177 μmmol/L). This study was approved by the months) was 98.2% (187/191), 99.3% (186/187), 100.0% (184/
Ethics Committee of Cardiovascular Institute and Fuwai 184), and 99.6% (161/162), respectively. The percentage of
Hospital, Peking University of Medical Sciences, and written valid home BP among family members in the regular salt
informed consent was obtained from all participants includ- group at every visit (including baseline, 3months visit,
ing 220 hypertensive patients and their family members (n = 6months visit, and 12months visit) was 98.4% (186/189),
380) prior to the study. The study was registered at clinical- 99.2% (181/183), 99.4% (176/177), and 100.0% (175/175),
trial.gov NCT00145756 in September 2005. respectively. The average of all valid readings collected during
three consecutive days at each visit was used in the study
analysis.
Study protocol
In family members, we defined hypertension as having a
An administrant randomly assigned all 220 selected house- home systolic blood pressure (HSBP) ≥135 mm Hg or a
holds to either the salt substitute group or the regular salt home diastolic blood pressure (HDBP) ≥85 mm Hg at
group with a computerized random number function home (20).
(Figure 1). The random allocation papers were concealed
in sequentially-numbered envelopes. Subsequent follow-up
Compliance measurements
visits were at 3, 6 and 12 months to check and encourage
compliance to the intervention salt (including regular salt We assessed the compliance of patients to trial salt
and salt substitute) by investigators and local practitioners. through measurement of urine sodium and potassium
If the hypertensive patient moved during the follow-up levels. A morning first fasting midstream urine sample
period they and all their family members were excluded. was collected from hypertensive patients and their families
The salt substitute consisted of 65% sodium chloride, 25% and frozen at −20°C at the baseline, 6th and 12th months.
potassium chloride, and 10% magnesium sulfate and the reg- All urine samples were shipped to the Center Laboratory
ular salt contained 100% sodium chloride (18). All trial salt of Fuwai Hospital, Peking University of Medical Sciences.
was manufactured, packaged, and labeled by the Beijing Salt The concentrations of morning fasting midstream urine
CLINICAL AND EXPERIMENTAL HYPERTENSION 3

Registration
220 hypertensive patients

Randomization
n=220 households (220 hypertensive patients, 380 family members)

Allocated to regular salt Allocated to salt substitute


RANDOMISED
n=110 households n=110 households
(110 hypertensive patients, (110 hypertensive patients,
189 family members) 191 family members)

Followed up n=109 households Followed up n=109 households


(109 hypertensive patients, 183 family FOLLOWED UP 3 (109 hypertensive patients, 187 family
members) MONTHS members)
Hypertensive patients: dislike the salt 1 Hypertensive patients: dislike the salt 1
Family members: lost to follow up 3# Family members: lost to follow up 2#
Marriage 1, go to college 1, divorce 1 Go to college 1, hospital 1, divorce 1

FOLLOWED UP 6 Followed up n=107 households


Followed up n=107 households MONTHS (107 hypertensive patients, 184 family
(107 hypertensive patients, 177 family members)
members) Hypertensive patients: hospital for fever 1,
Hypertensive patients: stroke 1, AMI 2
appendicitis 1 Family members: lost to follow up 3#

Followed up n=105 households FOLLOWED UP 12 Followed up n=102 households (hypertensive


(105 hypertensive patients, 175 family MONTHS patients 102, 162 family members)
members) Hypertensive patients: dislike the salt 1,
Hypertensive patients: nephritis 1, AMI nephrosis 1, AMI 2, stroke 1
1, Family members: Lost to contact 1, hospital 2
Family members: lost to follow up 2# Custody 1, marriage/divorce 3, go to college
4, lost to follow up 11

Data available for analysis Data available for analysis


HBP: 110 hypertensive patients, ANALYSED* HBP: 110 hypertensive patients,
186 family members 187 family members

Figure 1. Notice: 1. #The lost family members were passively withdrawn due to the loss of related hypertensive patients 2.* All participants that had complete data
and valid home blood pressure measurement at baseline were included in analysis. 3. HBP = home blood pressure. 4. CVD = cardiovascular disease. 5.AMI = acute
myocardial infarction.

sodium and creatinine were used to estimate 24-hour Statistics


urinary sodium according to Kawasaki formula (21).
The sample size Data from 220 patients with hypertension
Additionally, at each hypertensive patient’s visit, informa-
and 373 family members, who had valid home BP measure-
tion on compliance was also assessed with the question
ments at baseline, were analyzed on an intention-to-treat basis
‘What proportion of the household salt used during the
(ITT). In ITT analysis, we included every subject who was
preceding period was replaced by the trial salt?’ with
randomized according to the randomized treatment assign-
answers ‘all’, ‘nearly all’, ‘half’, ‘less than half’ or ‘none’.
ment. If a patient was not compliant with the protocol or
To ensure double-blinding, urine and serum potassium
withdrew from the study then, we used the baseline home BP
and sodium measurements were not reported to the inves-
values as the follow-up data. Sample size was determined as
tigators or local physicians except when serum potassium
follows: n = 2(Uα + Uβ)2 × SD2/d2 where the value of α is 0.05
was less than 3.5 mg/dl or more than 5.5 mg/dl. Over the
and β is set at 0.1. Standard deviation of systolic blood
course of the study, the treatment code was not broken.
pressure was 15 mm Hg. The expected differences (d) between
two group was 5.0 mm Hg, obtained from CSSS. Therefore,
the calculated n is 190. After consideration for lost to follow-
Other clinic measurements up (15%), an n of 220 was determined. All variables were
Baseline hypertensive patients’ body and weight were mea- tested for normality. Means ± standard deviations were
sured without heavy clothing and shoes. Body mass index reported for variables with a normal distribution. Median
was computed by weight (kg) divided by squared and inter-quartile ranges were reported for variables that do
height (m). not follow normal distributions, which were log transformed.
4 J. HU ET AL.

For comparison between intervention and control groups, Changes in home BP after intervention
Student’s Paired or Unpaired T-tests (data normally distrib-
The changes in home BP after intervention among 593 sub-
uted) or Mann-Whitney U test (data not normally distribu-
jects including 220 hypertensive patients and 373 family
ted) were applied for continuous variables, and X2 test was
members are shown in Figure 2. Home SBP was significantly
used for categorical variables. Analysis of covariance was
lower in the salt substitute group compared to the regular salt
performed to assess the net changes between the two groups
group in the 3rd month and persisted to the end of the trial in
after adjustment for baseline BP value and weight changes.
hypertensive patients (Figure 2A), but not in their family
We also performed subgroup analysis by age, baseline BP
members (Figure 2B). There were no detectable differences
level, and gender. General linear model for repeated measure
between groups for home DBP at any time point (all P > 0.1;
of analysis was used for comparing the differences in urine
Figure 2C and D).
electrolytes between groups. All analysis was performed with
the SPSS 13.0 statistical package (SPSS Inc., Chicago, Illinois,
USA). Statistical significance was set at α = 0.05 level.
Distributions of home BP response to regular salt and salt
substitute
Results The overall proportions of home SBP reductions were larger in
the salt substitute group than those in the regular salt group (X2
207 of the 220 selected households (98.60%) completed the = 17.981, P = 0.001). For example, home SBP decreased by 3, 5,
whole follow-up and all or nearly all of them adopted the trial 10 and more mm Hg among 13.7%, 10.8%, 26.5% and 13.7% of
salts during the intervention period. The follow-up rate was hypertensive patients and 19.0%, 17.1%, 13.3% and 8.2% of
98.6% in the hypertensive patients and 88.7% in their family family members after the salt substitute intervention; home
members. Withdrawal of hypertensive patients resulted in a SBP decreased by 3, 5, 10 and more mm Hg among 21.7%,
reluctance to continue the trial among their family members 10.2%, 22.6% and 5.7% of hypertensive patients and 29.8%,
and was the main reason for participant withdrawal 12.9%, 12.9% and 1.2% of family members after taking regular
(Figure 1). salt (Figure 3). Furthermore, home SBP fell by 4.2 mm Hg (95%
At baseline, 100% of the hypertensive patients and confidence interval 1.3–7.0) in hypertensive patients and
98.2% of family members had valid home BP measure- 1.7 mm Hg (95% confident interval −0.2 to 3.6) in family
ments. The baseline characteristics are shown in Table 1. members after adjustment for the baseline SBP value and
There were no significant differences between the salt weight at the end of the intervention. The home DBP response
substitute group and the regular salt group with respect to regular salt and salt substitute were similar (P > 0.05).
to gender, age, BMI, home SBP and DBP, hypertension
rate, household consumption of salt among the hyperten-
sive patients and their family members (all P > 0.05).
None of the hypertensive patient’s family members took The effects of salt substitute on home BP by gender, age
antihypertensive medicine during the intervention. The and baseline BP degree
rates of antihypertensive treatment were higher in the Subgroup analyses were conducted to explore the constancy
regular salt group than in the salt substitute group at of effect on the randomized treatment in different subgroups
each time point but were not significantly different except including age groups (age <60 years and age ≥60 years), sex
for the 3rd month visit in hypertensive patients (see sup- groups (male and female), and blood pressure categories
plementary file). Weight and weight changes were not (stage-1 hypertension and stage-2 hypertension in hyperten-
significantly different between the two groups during sive patients, hypertension, and normal blood pressure in
intervention (see supplementary file). family members).

Table 1. Baseline characteristics of subjects in regular salt and salt substitute groups.
Hypertensive patients Family Members
Salt substitute Salt substitute Salt substitute Salt substitute
(N = 187) (N = 187) (N = 187) (N = 187)
Age (years) 57.6 ± 10.1 57.1 ± 10.9 45.7 ± 17.4 45.5 ± 17.5
Men (%) 40.0 33.6 52.6 54.5
BMI (kg/m2) 28.3 ± 3.5 27.6 ± 3.3 25.2 ± 4.3 24.9 ± 3.8
Antihypertensive drug (%) 77.3 71.8 0 0
HP (%) - - 24.2 31.6
Home blood pressure
SBP(mm Hg) 141.4 ± 14.8 139.9 ± 14.4 124.9 ± 16.2 124.1 ± 15.3
DBP(mmHg) 84.1 ± 9.6 81.9 ± 8.5 75.6 ± 8.8 75.9 ± 10.0
Urine electrolyte*
Sodium(mmol/L) 127.2 125.1 126.1 125.8
(98.5–153.2) (80.0–149.8) (96.7–152.6) (81.1–151.2)
Potassium (mmol/L) 24.5 21.2 24.1 20.5
(14.0–25.3) (14.3–33.1) (13.8–24.8) (13.2–31.5)
Salt consumptions (bags/household) 2.1 ± 0.5 2.0 ± 0.4
*Values are median (quartile range).
CLINICAL AND EXPERIMENTAL HYPERTENSION 5

A B
165 regular salt salt substitute
145
*P<0.05

Home SBP (mm Hg)


140
155 *P<0.05 *P<0.05
135
145 130
125
135 120
115
125
110
105
115 month 0 month 3 month 6 month 12
month 0 month 3 month 6 month 12

c D
90
95
Home DBP (mm Hg)

85
90
80
85 75
80 70

75 65
60
70 month 0 month 3 month 6 month 12
month 0 month 3 month 6 month 12

Month of the follow-up visit


Figure 2. Mean home SBP (top) and home DBP (bottom) at each visit among 593 subjects including 220 hypertensive patients (A and C) and 373 family members (B
and D). Home SBP was significantly different between the two groups at the 3-, 6-, and 12-month follow-up time points (*P < 0.05).

Regular salt in hypertensive patients Salt substitute in hypertensive patients Regular salt in family members Salt substitute in family members

Regular salt in hypertensive patients Salt substitute in hypertensive patients Regular salt in family members Salt substitute in family members

Figure 3. The distributions of home SBP and DBP response to regular salt and salt substitute in hypertensive patients and their family members.

In hypertensive patients, the baseline-adjusted SBP 2 hypertension group to the stage-1 hypertension group
reduction was significantly greater in females than in (0.5 mm Hg v. −0.2 mm Hg, P = 0.013) (Figure 4).
males (4.3 mm Hg v. 1.2 mm Hg, P = 0.019), in the age In family members, the adjusted SBP difference was
≥60 years group than the age <60 years group (6.3 mm Hg larger in the age ≥60 years group than the age <60 years
v. 2.5 mm Hg, P = 0.032), and in stage-2 hypertension than group (2.8 mm Hg v. 0.3 mm Hg, P < 0.05), and was
in stage-1 hypertension (7.6 mm Hg v. 3.7 mm Hg, P = greater in families with hypertension than those without
0.022). Significance was still observed after adjustment for hypertension (2.4 mm Hg v. 0.1 mm Hg, P < 0.05).
baseline-DBP and weight changes, in each subgroup, when However, adjusted SBP differences were of smaller magni-
comparing the age≥60 years group to the age <60 years tude in men than in women (0.8 mm Hg v. 2.0 mm Hg, P
group (0.3 mm Hg v.-0.08 mm Hg, P < 0.01) and the stage- < 0.05). The baseline-adjusted DBP differences were not
6 J. HU ET AL.

Figure 4. The Changes in blood pressure from baseline after adjustment for baseline blood pressure values in subgroups of hypertensive patients and their families.
*Net difference in change from baseline after adjustment of baseline blood pressure values between study groups.

significantly different between different age groups and salt group during the intervention (all P < 0.05). The urine sodium
blood pressure levels and gender (all P > 0.05) (Figure 4). concentration decreased 8.0 mmol/l (95% confidence interval
−9.6–25.7), the urine potassium concentration increased
7.6 mmol/l (95% confidence interval 0.8–14.4), the sodium-to-
Changes in urinary electrolytes potassium ratio decreased 1.1 (95% confidence interval 0.2–2.0)
As displayed in Table 2, urine sodium concentration, sodium- and the 24-hour sodium excretion estimates decreased 1140.1 mg/
potassium ratio and the 24-hour sodium excretion estimates were day (95% confidence interval 237.7 to 2042.5) during the inter-
significantly lower and the urine potassium concentration was vention in the salt substitute group compared to the regular salt
significantly higher in the salt substitute group than the regular group, after adjustment for the baseline value.

Table 2. Urinary sodium and potassium excretion and the ratio of urinary sodium and urinary potassium and at baseline and during intervention among hypertensive
patients and their families. Values are median (quartile range).
Month 0 Month 6 Month 12 P
Sodium (mmol/L)
Regular salt group (n = 299) 126.9(97.1, 152.0) 126.0(81.9, 166.1) ‡ 124.2(80.2, 160.6) <0.05
Salt substitute group(n = 301) 125.5(80.4, 150.3) 113.1(74.2, 147.0) 122.5(83.9, 160.3)
Potassium (mmol/L)
Regular salt group(n = 299) 24.3(13.7, 24.3) 29.8(20.3, 43.5)‡ 28.6(17.8, 55.6) ‡ <0.05
Salt substitute group(n = 301) 20.7(13.6, 32.4) 36.9(26.7,54.6) 40.5(24.7, 70.5)
Sodium/Potassium
Regular salt group(n = 299) 5.4(3.7, 7.7) 4.4(3.0, 6.1) ‡ 4.0(2.6, 6.4) ‡ <0.05
Salt substitute group(301) 5.4(3.9, 7.5) 2.9(2.1, 4.0) 2.5(1.7, 0.3)
Creatinine (mmol/L)
Regular salt group(n = 299) 6.6(4.3, 10.2) 6.7(4.5, 10.6) 6.38(3.1, 12.2) 0.23
Salt substitute group(n = 301) 6.5(3.9,9.8) 6.1(4.1, 8.6) 7.13(3.9, 13.8)
24-h sodium excretion estimated (mg/day)
Regular salt group(n = 299) 4108.2(2598.7, 5098.2) 4026.8(2506.3, 5449.3) 3477.1(2183.3, 2032.1) ‡ <0.05
Salt substitute group(n = 301) 4187.3(2746.3, 5578.1) 4080.4(2937.5, 5159.0) 3890.1(2183.6, 8012.6)
‡Comparison of urinary sodium, urinary potassium, and the ratio of urinary sodium and urinary potassium between two groups were significantly different (P < 0.05).
CLINICAL AND EXPERIMENTAL HYPERTENSION 7

Discussion present study we observed a greater reduction of home SBP


among those older in age and females. However, our findings
As the leading global risk factor, hypertension accounts for a are inconsistent with a previous study, which found signifi-
loss of 174 million disability-adjusted life years (DALYs) every cant effects in participants 40 to 70 years of age and similar
year (22). However, the rates of awareness, treatment, and beneficial clinical BP reducing effects in both males and
control are all substantially lower in low- and middle-income females (15). However, there is substantial evidence demon-
countries than in high-income countries (23). Salt substitutes strating stronger BP reducing effects among elderly people
with reduced sodium and added potassium and/or calcium than young people (35) and women compared to men (14)
can lower clinical BP in Chinese populations (15,24–28), and from a reduction in sodium intake. It was reported that salt-
have been considered to have greater benefits in developing sensitivity is more common among older individuals and
countries where most dietary salt is consumed in foods significantly increases with age (36). Moreover, physiological
cooked at home. However, few studies have examined studies have suggested that female hormones (estrogen and
whether a salt substitute can lower home BP. progesterone) might be associated with increased renal
To our knowledge, only one previous study has investi- sodium reabsorption and water retention (37). Furthermore,
gated home BP response to a salt substitute, finding a sig- sex hormone genes variants have been strongly correlated
nificant reduction in home SBP among hypertensive patients with BP response to a dietary-sodium intervention (38).
(11). Because Chinese people usually eat together with family These studies help to explain why certain subgroups saw
members, a salt substitute might positively affect all members greater reductions in home BP.
of the household. To our knowledge, the present study is the The present study has several limitations. Firstly, we did
first to explore the effects of a salt substitute on home BP not collect a 24-hour urine sample, but did get the first
among family members. In the present study, we found that morning fasting midstream urine sample in hypertensive
home BP did not significantly change in all family members. patients and their families to estimate 24-hour sodium excre-
Furthermore, in the subgroup-analysis, home SBP was signif- tion with the Kawasaki formula, which is considered to have
icantly decreased in family members with hypertension, but the best agreement and least amount of bias in estimating
not in family members with normal BP (Figure 4b). These excretion (21). Also, salt consumption between the regular salt
results are inconsistent with three previous studies which, had and salt intervention groups in the present study were similar.
reported that a salt substitute lowered clinical BP in normo- If possible, future studies should consider the use of a 24-hour
tensive people (25–27). This discrepancy may result from urine sample or dietary recalls to get more reliable salt con-
differing BP measuring methods (25–27), duration of inter- sumption data. Secondly, mean BP in the control group also
vention (26,27), and/or proportion of constituents in salt dropped after intervention because of seasonal BP change or
substitutes (25,26). While one report suggests that salt-restric- regression to the mean. The China Salt Substitute Study
tion education has a stronger reduction on clinical BP than (CSSS) observed similar seasonal BP change (24). However,
home BP (29), it is important to note that clinical BP may the use of a randomized controlled double-blinding study
overestimate or underestimate the effects of treatment (30,31). design protected the validity of the study conclusion from
These overestimations or underestimations may be due to the seasonal change and regression to the mean. Thirdly, the
several factors such as poor reproducibility, observer bias, duration of intervention may be too short. Compared with the
white-coat phenomenon, and placebo effects (30,31). use of antihypertensive medications, BP response to a salt
Moreover, a longer duration of intervention may lead to the substitute is a slow process. Although, in the CSSS study,
significant BP reductions observed (26,27). It has been shown non-significant reductions in DBP were found after a one-
that, salt substitutes reduced both clinical SBP and DBP at 18- year intervention (24) it could take at least 18 months for the
months after extending a 1- year follow-up period to two- or salt substitute to show its BP lowering effects (27). Fourthly,
three-years (15,27). Taken together, these studies suggest that the study is currently limited to northern China. The preva-
the effects of salt substitutes are variable and a longer duration lence of hypertension and salt intake are higher in Northern
may be required to fully observe the home BP response to a China than in Southern China (16). When exploring the
salt substitute. effects of a salt substitute on home blood pressure in hyper-
Our results indicate that the reduction of home SBP was tensive patients and their families, significant effects may be
larger in subjects with higher baseline BP, older age and found easier among people in Northern China than other
female gender. These results are consistent with those from areas. Regardless, we anticipate that increasing both the sam-
a dietary sodium intervention study which reported clinical ple size and number of research groups will yield similar
BP (32). Furthermore, previous studies have found that results and make them more generalizable.
hypertensive patients had greater clinical SBP reductions In conclusion, this study provides evidence that a salt
than people with normal BP after a salt substitute intervention substitute had no influence on home BP among the normo-
(25–27). The differences of BP response to a salt substitute tensive, but was a simple, sustainable, well accepted, and
among the different BP categories may be due to variations in convenient measure to combat high blood pressure, especially
salt-sensitivity. Recent studies have shown a greater BP reduc- in older aged individuals, women, and high blood pressure
tion in salt-sensitive adolescents than in non-salt-sensitive patients. Identifying subgroups that are more sensitive to salt
adolescents after using salt substitutes (26) and that a greater substitute will allow us to develop targeted dietary interven-
proportion of hypertensive patients than normotensive sub- tions for the treatment and prevention of hypertension. The
jects were sodium-sensitive (33,34). Additionally, in the Chinese Dietary and Nutritional Development Regulation
8 J. HU ET AL.

2014–2020 suggested “develop nutritional food low in sodium to dietary sodium intervention in the GenSaltstudy. J Hypertens.
and fat” as a key goal. To this end, this study provides support 2009;27(1):48–54.
15. Zhou B, Webster J, Fu LY, Wang HL, Wu XM, Wang WL, Shi JP.
for a population based intervention where a salt substitute can
Intake of low sodium salt substitute for 3years attenuates the
be provided instead of regular salt. Salt substitute interven- increase in blood pressure in a rural population of North China-
tions are important in that they can be implemented on both A randomized controlled trial. Int J Cardiol 2016;215:377–82.
population and individual based levels with positive impacts. 16. Zhao L, Stamler J, Yan LL, Zhou B, Wu Y, Liu K, Daviglus ML,
Dennis BH, Elliott P, Ueshima H, Yang J, Zhu L, Guo D;
INTERMAP Research Group. Blood pressure differences between
northern and southern Chinese: role of dietary factors: the
Acknowledgments International Study on Macronutrients and Blood Pressure.
Hypertension 2004;43(6):1332–37.
This work was supported by the Danone Nutrition Fund in People’s 17. Hu J, Jiang X, Li N, Yu X, Perkovic V, Chen B, Zhao L, Neal B,
Republic of China. Local principal investigators of this study were as Wu Y. Effects of salt substitute on pulse wave analysis among
follows: Beijing, The Community Health Service Center of Yinghai, individuals at high cardiovascular risk in rural China: a rando-
Daxing District: Qi Jianhua, Pan Rujun, The Community Health mized controlled trial. Hypert Res 2009;32:282–88.
Service Center of Taihe, Daxing District: Chen Baojun, Pan Zhentang. 18. Li N, Prescott J, Wu Y, Barzi F, Yu X, Zhao L, Neal B. The effects
of a reduced-sodium, high-potassium salt substitute on food taste
and acceptability in rural northern China. Br J Nutr 2009;101
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