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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
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
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.
Registration
220 hypertensive patients
Randomization
n=220 households (220 hypertensive patients, 380 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.
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
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
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
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
References (7):1088–93.
19. Jihong H, Shan W, Weidong H, Wang Y. Evaluation for the
1. Palafox B, McKee M, Balabanova D, AlHabib KF, Avezum AJ, OMRON HEM-752 electronic sphygmomanometer. Journal of
Bahonar A, et al. Wealth and cardiovascular health: a cross-sec- Ningxia Medical College 2008;30(6):824–26.
tional study of wealth-related inequalities in the awareness, treat- 20. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green
ment and control of hypertension in high-, middle- and low- LA, Izzo JL Jr., Jones DW, Materson BJ, Oparil S, Wright JT Jr.,
income countries. Int J Equity Health 2016;15(1):199–212. et al., Joint National Committee on Prevention, Detection,
2. World Health Organization. Global Action Plan for the Evaluation, and Treatment of High Blood Pressure. National
Prevention and Control of Noncommunicable Diseases. Geneva. Heart, Lung, and Blood Institute; National High Blood Pressure
Switzerland: WHO; 2013; 2013-2020. Education Program Coordinating Committee. Seventh report of
3. Xu JW Study on Salt Reduction Strategy for China. [Dissertation] the Joint National Committee on Prevention, Detection,
Bejing, China: China Center of Diseases Control; 2014. Evaluation, and Treatment of High Blood Pressure.
4. Hipgrave DB, Chang S, Li X, Salt WY. Sodium Intake in China. Hypertension 2003;42(6):1206–52.
Jama 2016;315(7):703–05. 21. Mente A, O’Donnell MJ, Dagenais G, Wielgosz A, Lear SA,
5. Sanjiv Agarwal VL, Fulgoni III, Spence L, Samuel P. Sodium McQueen MJ, et al. Validation and comparison of three formulae
intake status in United States and potential reduction modeling: to estimate sodium and potassium excretion from a single morn-
an NHANES 2007–2010 analysis. Food Sci Nutr 2015;3(6):577–85. ing fasting urine compared to 24-h measures in 11 countries. J
6. Tsunematsu N, Ueshima H, Okuda N, et al. The actual amount of Hypertens 2014;32:1005–14.
reductions in salt intake among those on a restricted salt diet: 22. Murray CJ, Lopez AD. Measuring the global burden of disease. N
from the INTERMAP Japan. J Jpn Soc Prev Cardiovasc Dis Engl J Med 2013;369(5):448–57.
2004;39:149–55. 23. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K,
7. Peng YG, Li W, Wen XX, Li Y, Hu JH, Zhao LC. Effects of salt et al. Global disparities of hypertension prevalence and control: a
substitutes on blood pressure: a meta-analysis of randomized systematic analysis of population-based studies from 90 countries.
controlled trials. Am J Clin Nutr 2014;11(6):1448–54. Circulation 2016;134(6):441–50.
8. Stergiou GS, Skeva II, Zourbaki AS, Mountokalakis TD. Self 24. China Salt Substitute Study Collaborative Group. Salt substi-
-monitoring of blood pressure at home: how many measurements tute: a low-cost strategy for blood pressure control among rural
are needed?. J Hypertens 1998;16:725–31. Chinese. A randomized, controlled trial. J Hypertens 2007;25
9. Stergiou GS, Zourbaki AS, Skeva II, Mountokalakis TD. White (10):2011–18.
coat effect detected using self-monitoring of blood pressure at 25. Zhou X, Liu JX, Shi R, Yang N, Song DL, Pang W, et al.
home: comparison with ambulatory blood pressure. Am J Compound ion salt, a novel low-sodium salt substitute: from
Hypertens 1998;11:820–27. animal study to community-based population trial. Am J
10. Vaur L, I I D, Dutrey-Dupagne C, Genès N, Chatellier G, Bouvier- Hypertens 2009;22(9):934–42.
d’Yvoire M, Elkik F, Ménard J. Superiority of home blood pres- 26. Mu J, Liu Z, Liu F, Xu X, Liang Y, Zhu D. Family-based rando-
sure measurements over office measurements for testing antihy- mized trial to detect effects on blood pressure of a salt substitute
pertensive drugs. Blood Press Monit 1998;3:107–14. containing potassium and calcium in Hypertensive adolescents.
11. Ji-Hong H, Lian-Cheng Z, Xian L, Yang-Feng W. Effect of salt Am J Hypertens 2009;22:943–47.
substitution on blood pressure using home measurements in 27. Zhou B, Wang HL, Wang WL, Wu XM, Fu LY, Shi JP. Long-term
essential hypertensive patiens; a double-blinded randomized con- effects of salt substitute on blood pressure in a rural north Chinese
trolled trial. Chin J Hypertens 2014;22(1):42–46. population. J Hum Hypertens 2013;27(7):427–33.
12. Fang Zhao, Puhong Zhang, Lu Zhang, Wenyi Niu, Jianmei Gao, 28. Zhao X, Yin X, Li X, Yan LL, Lam CT, Li S, et al. Using a low-
Lixin Lu, Caixia Liu, Xian Gao. Consumption and sources of sodium, high-potassium salt substitute to reduce blood pressure
dietary salt in family members in Beijing. Nutrients. 2015;7 among Tibetans with high blood pressure: a patient-blinded ran-
(4):2719–30. domized controlled trial. PLoS One 2014;9(10):e110131.
13. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, 29. Nakano M1, Eguchi K, Sato T, Onoguchi A, Hoshide S, Kario K.
Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure Effect of intensive salt-restriction education on clinic, home, and
lowering for prevention of cardiovascular disease and death: a ambulatory blood pressure levels in treated hypertensive patients
systematic review and meta-analysis. Lancet 2016;387 during a 3-month education period. J Clin Hypertens
(10022):957–67. (Greenwich) 2016;18(5):385–92.
14. He J, Gu D, Chen J, Jaquish CE, Rao DC, Hixson JE, Chen JC, 30. Appel LJ, Stason WB. Ambulatory blood pressure monitoring and
Duan X, Huang JF, Chen CS, et al., GenSalt Collaborative blood pressure self-measurement in the diagnosis and manage-
Research Group. Gender difference in blood pressure responses ment of hypertension. Ann Intern Med 1993;118:867–82.
CLINICAL AND EXPERIMENTAL HYPERTENSION 9
31. Mansoor GA, White WB. Contribution of ambulatory blood 35. Vollmer WM, Sacks FM, Ard J, Appel LJ, Bray GA, Simons-
pressure monitoring to the design and analysis of antihypertensive Morton DG, Conlin PR, Svetkey LP, Erlinger TP, Moore TJ,
therapy trials. J Cardiovasc Risk 1994;1:136–42. et al., Collaborative Research Group. Effects of diet and sodium
32. He J, Gu D, Chen J, Jaquish CE, Rao DC, Hixson JE, Chen JC, intake on blood pressure: subgroup analysis of the DASH-Sodium
Duan X, Huang JF, Chen CS, et al., GenSalt Collaborative trial. Ann Intern Med. 2001;135(12):1019.
Research Group. Gender difference in blood pressure responses 36. Weinberger MH, Fineberg NS. Sodium and volume sensitivity of
to dietary sodium interventionin the GenSalt Study. J Hypertens. blood pressure. Age and Pressure Change over Time.
2009 Jan;27(1):48–54. Hypertension 1991;18(1):67–71.
33. Sullivan JM, Prewitt RL, Ratts TE. Sodium sensitivity in normo- 37. Stachenfeld NS, Taylor HS. Effects of estrogen and progesterone
tensive and borderline hypertensive humans. Am J Med Sci administration on extracellular fluid. J Appl Physiology
1988;295(4):370–77. 2004;96:1011–18.
34. Wright JT Jr., Rahman M, Scarpa A, Fatholahi M, Griffin V, Jean- 38. Kelly TN1, Rebholz CM, Gu D, Hixson JE, Rice TK, Cao J, Chen J,
Baptiste R, et al. Determinants of salt sensitivity in black and Li J, Lu F, Ma J, et al. Analysis of sex hormone genes reveals gender
white normotensive and hypertensive women. Hypertension differences in the genetic etiology of bloodpressure salt sensitivity:
2003;42:1087–92. the GenSalt study. Am J Hypertens 2013;26(2):191–200.