PLoS ONE plos plosone PLOS ONE 1932-6203 Public Library of Science San Francisco, CA USA 10.1371/journal.pone.0311908 PONE-D-24-07382 Research Article Medicine and health sciencesVascular medicineBlood pressure Physical sciencesChemistryChemical compoundsSaltsSodium chloride Biology and life sciencesNutritionDiet Medicine and health sciencesNutritionDiet Biology and life sciencesPhysiologyPhysiological processesExcretion Biology and life sciencesAnatomyBody fluidsUrine Medicine and health sciencesAnatomyBody fluidsUrine Biology and life sciencesPhysiologyBody fluidsUrine Medicine and health sciencesVascular medicineBlood pressureHypertension Biology and life sciencesPsychologyPsychological attitudes Social sciencesPsychologyPsychological attitudes Biology and life sciencesNutritionDietFood Medicine and health sciencesNutritionDietFood Community-based intervention for monitoring of salt intake in hypertensive patients: A cluster randomized controlled trial Salt meter utilization in community and blood pressure control https://orcid.org/0000-0001-8228-5430 Sonuch Pitchaporn Data curation Writing – original draft 1 Aekplakorn Wichai Conceptualization Formal analysis Methodology Writing – review & editing 2 Pomsanthia Nophatee Data curation 3 Boonyagarn Natthida Data curation Project administration 3 Makkawan Siripak Conceptualization Supervision 4 Thongchai Suchada Project administration Supervision 4 Tosamran Wasinee Supervision Visualization 4 Kunjang Ananthaya Methodology Project administration 3 https://orcid.org/0000-0003-2119-8987 Kantachuvesiri Surasak Conceptualization Funding acquisition Project administration Writing – review & editing 1 3 * Division of Nephrology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Department of Community Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Thai Low Salt Network, The Nephrology Society of Thailand, Bangkok, Thailand Office of Disease Prevention and Control 3, Nakhon Sawan, Thailand Gao Peng Editor Army Medical University, CHINA

The authors have declared that no competing interests exist.

 * E-mail: surasak.kan@mahidol.ac.th 22 11 2024 2024 19 11 e0311908 22 3 2024 26 9 2024 2024 Sonuch et al This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background

Excessive sodium intake is associated with high blood pressure and an increased risk of cardiovascular disease. However, reducing dietary salt has been challenging due to a lack of awareness and a high threshold in detecting saltiness.

 Objectives

The goal of this study is to evaluate the effectiveness of a combined intervention (intensive dietary education, food reformulation, environmental changes to facilitate salt reduction, and salt meter utilization), in comparison to standard education only, on salt intake and blood pressure.

 Methods

A cluster randomized-controlled trial was conducted on 219 hypertensive adults aged 18 to 70 years in Uthaithani, Thailand. Participants were randomized 1:1 into the intervention group (n = 111) and the control group (n = 108).

 Results

There were no differences in baseline characteristics between groups. The mean systolic and diastolic blood pressure was 143.6 and 82.1 mmHg and 142.2 and 81.4 mmHg in the intervention group, and the control group, respectively. The median 24-hour urinary sodium excretion was 3565 and 3312 mg/day, in the intervention and the control group, respectively. After 12 weeks, the change in systolic blood pressure was -13.5 versus -9.5 mmHg (P = 0.030) and diastolic blood pressure was -6.4 versus -4.8 mmHg (P = 0.164) in the intervention and control groups, respectively. Moreover, a reduction in 24-hour urine sodium excretion was observed [-575 versus -299 mg/day in the intervention and control groups, respectively (P = 0.194)]. The change in 24-hour urine sodium excretion was statistically significant and reduced from baseline in the intervention group (P = 0.004). The dietary salt intake was significantly improved and was statistically different between groups (P = 0.035).

 Conclusions

The combined intervention significantly decreased systolic blood pressure and showed a trend towards reduced urine sodium excretion in hypertensive patients. These comprehensive approaches may be beneficial in reducing blood pressure and salt intake in the community.

 Clinical trial registration

This trial was registered at Clinicaltrials.gov with the identifier NCT05397054. https://classic.clinicaltrials.gov/ct2/show/NCT05397054

 http://dx.doi.org/10.13039/501100009061 Thai Health Promotion Foundation 64-00255-0002 https://orcid.org/0000-0003-2119-8987 Kantachuvesiri Surasak World Health Organization (WHO) office, Thailand 2021/1159185-0 https://orcid.org/0000-0003-2119-8987 Kantachuvesiri Surasak This study was financially supported by the Thai Health Promotion Foundation No. 64-00255-0002 and World Health Organization (WHO) office, Thailand, registration 2021/1159185-0 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability All relevant data are within the paper and its Supporting Information files Introduction

Non-communicable diseases (NCDs) are a global burden and a major cause of morbidity and mortality. NCDs are responsible for approximately 60% of all deaths and 43% of the global disease burden [1]. One of the most urgent public health issues related to NCDs is hypertension, which increases the risk of cardiovascular disease. High sodium intake which is the top three dietary risk factors was responsible for morbidity and mortality globally [2].

Excessive sodium intake is associated with high blood pressure [3, 4]. Consuming more dietary sodium than the World Health Organization’s recommended daily amount of 2,000 milligrams is a risk factor for hypertension, cardiovascular disease, chronic kidney disease and is related to mortality [1]. According to the Prospective Urban Rural Epidemiology (PURE) study, 1-gram increment in urine sodium excretion was found to be correlated with an increase of 2.11 mmHg and 0.78 mmHg in systolic and diastolic blood pressure, respectively [5]. A reduction of dietary sodium intake can lead to lower blood pressure and lower cardiovascular morbidity and mortality [6–9].

According to a recent national survey in Thailand, dietary sodium consumption is 3,636 mg/day, which is nearly twice the recommended amount [10]. Most sodium consumption is derived from seasoning such as salt, fish sauce, soy sauce and seasoning powder. More than 60% of sodium is dissolved in the form of soup or curry. Therefore, reducing the use of seasoning, sauces, and soup can greatly reduce sodium consumption.

Dietary education and reformulation are effective methods for changing consumer behavior. However, these approaches are challenging for individuals to implement without adequate support or resources. One simple tool that can help individuals monitor their sodium intake is a salt meter, which measures the amount of sodium in food and beverages.

In addition, communities can play a vital role in reducing sodium consumption by promoting low-sodium options in restaurants, and implementing policies that reduce the sodium content of processed foods. By combining individual efforts with community-wide strategies, reducing the burden of sodium-related health problems can be achieved.

This study, was aimed to evaluate the effectiveness of comprehensive approaches that include intensive dietary education about risk of high sodium intake, dietary reformulation, environmental change in the community, and self-monitoring of salt intake by salt meter compared to standard education alone in the community settings. The primary outcome is the change in 24-hour urine sodium excretion. Secondary outcomes include changes in blood pressure, as well as evaluations of changes in knowledge, attitudes, and behaviors after a complete 12-week follow-up.

 Materials and methods Study design

The study was a cluster randomized controlled trial. The intervention group was assigned to received intensive dietary education, dietary reformulation, environmental changes in community, and self-monitoring of salt intake by salt meter. The control group received standard education only. Participants were not blinded because the interventions could not be masked. The study protocol was approved by the Human Research Ethics Committee, Faculty of Medicine Ramathibodi Hospital, Mahidol University (COA. MURA2021/1004). This trial was registered at Clinicaltrials.gov with the identifier NCT05397054.

 Participants

The participants included in this study were aged between 18–70 years and had a diagnosis of hypertension (systolic blood pressure ≥130 or diastolic blood pressure ≥ 80 mmHg) [11]. Participants with end-stage kidney disease, pregnancy, or breastfeeding status, recent adjustment of any antihypertensive drugs or diuretics within 2 weeks prior enrollment and used salt supplements were excluded. During the conduction of the trial, participants were not allowed to adjust their antihypertensive or diuretic medication. If participants had systolic blood pressure exceeding 180 mmHg or presented with hypertensive emergencies, they were excluded from the study.

 Trial conduction

The trial was conducted in Uthaithani, Thailand from 10th of January to 13th of June 2022. Participants were recruited from twelve clusters (villages) in six healthcare centers, each serving a different community, including Muang Uthaithani, Nam Suem-Muang Uthaithani, Nong Chang, Khao Pathawi-Thap Than, Kokmo-Thap Than, and Paikeaw-Sawangarom. Each health center was responsible for 10–12 villages. We used a random number generator, to assign a random number (1, 2) to each village (cluster). The villages assigned the number 1 were the intervention group, and the villages assigned the number 2 were the control group. A total of 6 clusters were randomly allocated to the intervention group and another 6 clusters to the control group. A total of 20 patients meeting the eligible criteria were randomly recruited, using the random number generator, in each cluster. Informed consent was obtained from all participants. (Fig 1).

10.1371/journal.pone.0311908.g001 Flow diagram of participants.

Baseline characteristics were collected, including age, sex, education, occupation, weight, height, waist circumference and medical history. Blood pressure was measured using an automatic blood pressure monitoring device (Omron HEM-7130-L) after 15 minutes of rest. Three measurements of blood pressure were recorded, and the average of both systolic and diastolic blood pressure were calculated. In addition, all participants were assessed using a standard questionnaire on their knowledge, attitude, and behavior, related to dietary consumption. The questionnaire was developed according to the local context and its content validity was assessed by 3 experts. It was tested for reliability, with the instrument achieving a Cronbach’s alpha coefficient of 0.79 [12]. Participants were asked to collect 24-hour urine, starting with the second void, and including the first void on the next day.

In the intervention group, participants received four comprehensive interventions. First, intensive dietary education, participants received education from nurses and dietitians about high sodium intake, sources of sodium, and nutritional ingredients for 2 hours on day 0 and for 1 hour at 4 and 8 weeks. Second, dietary reformulation, they were taught to cook low-sodium recipes for home cooking. Third, environmental changes in the community, we educated and encouraged vendors to provide low sodium menus to community members. Fourth, using a salt meter, the participants were advised to utilize a salt meter provided to monitor and record the salt levels in their meals at least three times per week. The level of salt in food was reported as high, medium, and low. The salt meter used in this study was developed from Faculty of Engineering, Mahidol University, Thailand [13]. Participants in the control group received only standard education for blood pressure control. Blood pressure was evaluated in both groups every four weeks. The trial had a follow-up period of 12 weeks.

At 12 weeks, all participants were reevaluated regarding their knowledge, attitudes, and behaviors related to dietary intake using the same standard questionnaire. In addition, 24-hour urine samples were collected to evaluate urine sodium and creatinine excretion.

 Statistical analysis

Sample size was calculated with 90% statistical power and 5% alpha error, based on a previous study [14] to detect the mean change in blood pressure of 5 mmHg among intervention group and 0 mmHg among control group (standard deviation 5 mmHg). The design effect was calculated using the formula 1+(k-1)rho, where k represented the size of each cluster (20) and rho was the intracluster correlation (0.2). For cluster randomization, a sample size of 100 was required. Accounting for a 20% dropout rate, the final sample size of 120 participants per group was determined to provide sufficient power for detecting outcomes.

n=(a+b)2SDi2+SDc2mi−mc2

a = Z alpha = 1.96, b = Z1-beta = 1.28, SD = standard deviation of BP for intervention and control, mi-mc = mean changes of BP between intervention and control.

Baseline characteristics were evaluated and displayed in numbers with percentages, mean ± standard deviation (SD) or median with interquartile range (IQR). Categorical variables were analyzed using Fisher’s exact test when expected values were less than 5, while continuous variables were analyzed using the student’s t-test with 2-tailed test. The primary outcomes were evaluated using the Wilcoxon rank-sum test, while the Wilcoxon signed-rank test was used to compare urine sodium excretion within group between pre and post intervention and between two groups. We used an intention to treat analysis. Participants with incomplete data were excluded in the analysis. The change of blood pressure was performed with linear mixed-effects model (LMM) since the study measured blood pressure (BP) multiple times on each participant before and after intervention. LMMs account for the correlation between these repeated measures within each participant. We used an unstructured correlation structure.

T-test was used to compare the changes in knowledge, attitudes, and behaviors of sodium intake. In addition, the changes of variables between group and associated test of effect were estimated by LMM regression adjusted for clustering and baseline: age, sex, education, occupation, weight, height, body mass index and waist circumference with maximum likelihood estimation and accounting for missingness. Statistical significance was set at P value <0.05. All analyses were performed using STATA version 17.

 Results

240 participants were enrolled from 6 clusters/group and 219 completed follow-up (111 participants from six clusters and 108 participants from another six clusters in the intervention and the control group, respectively) (Fig 1). Demographic data and baseline characteristics are shown in Table 1. The mean age was approximately 60 years old. Most participants in the study were female as they were more willing to participate in the research than men. The mean systolic and diastolic blood pressure was 143.6 and 82.1 mmHg in the intervention group, while for the control group, the mean systolic and diastolic blood pressure was 142.2 and 81.4 mmHg, respectively. The median of 24-hour urinary sodium excretion was 3565 and 3312 mg/day, in the intervention and the control group, respectively. Fewer patients completed primary education, however, there were more patients with bachelor’s degrees in the intervention group. In addition, the intervention group had a higher body weight, body mass index and waist circumference 1.

10.1371/journal.pone.0311908.t001 Demographic and baseline characteristics.
Baseline Characteristics Intervention (111) Control (108) P value
Age, mean ± SD (years) 60.0 ± 7.5 60.2 ± 7.5 0.883
Sex 0.121
• Female (%) 90 (81.1) 78 (72.2)
• Male (%) 21 (18.9) 30 (27.8)
Education 0.022*
• Uneducated (%) 13 (11.7) 10 (9.3) 0.554
• Primary school (%) 62 (55.9) 79 (73.2) 0.008*
• Secondary school (%) 26 (23.4) 17 (15.7) 0.152
• Bachelor degrees (%) 10 (9.0) 2 (1.9) 0.020*
Occupation 0.818
• Unemployed (%) 32 (28.8) 33 (30.6) 0.780
• Agriculturist, Employee (%) 77 (69.4) 72 (66.7) 0.668
• Government employee (%) 2 (1.8) 3 (2.8) 0.680
Weight, mean ± SD (kg) 70.0 ± 14.1 64.6 ± 12.5 0.003*
Height, mean ± SD (cm) 157.4 ± 7.5 156.4 ± 7.4 0.320
BMI, mean ± SD (kg/m2) 28.2 ± 4.8 26.3 ± 4.4 0.004*
Waist circumference, mean ± SD (cm) 94.1 ± 11.3 89.9 ± 9.9 0.004*
Blood pressure
• Systolic, mean ± SD (mmHg) 143.6 ± 13.4 142.2 ± 12.2 0.405
• Diastolic, mean ± SD (mmHg) 82.1 ± 9.7 81.4 ± 11.5 0.622
Other underlying diseases
• Diabetic mellitus (%) 37 (33.3) 28 (25.9) 0.230
• Dyslipidemia (%) 71 (64.0) 65 (60.2) 0.564
• Cardiovascular disease (%) 5 (4.5) 1 (0.9) 0.213
• Chronic kidney disease (%) 6 (5.4) 2 (1.9) 0.280
• Stroke (%) 4 (3.6) 1 (0.9) 0.369
• Chronic obstructive pulmonary disease (%) 1 (0.9) 1 (0.9) 1.000
24 hours urine
• Volume, median (IQR) (ml) 2050 (1410–2910) 1700 (1235–2555) 0.047*
• Sodium excretion, median (IQR) (mmol/24h) 155 (121–215) 144 (107.5–191.5) 0.096
• Sodium excretion, median (IQR) (mg/24h) 3565 (2783–4945) 3312 (2473–4405) 0.096
• Na/Cr ratio, median (IQR) (mg/mg) 3.6 (2.9–4.8) 3.4 (2.6–4.5) 0.346

*P value <0.05, statistical significance

 The changes in urinary sodium excretion and blood pressure

For the primary outcome, the difference in 24-hour urinary sodium excretion between groups was -276 mg/day, but this was not statistically significant (P = 0.194). The difference in the change of urinary sodium between two groups, adjusted for clustering and baseline variables, was not statistically different (P = 0.117) as shown in Table 2. However, 24-hour urinary sodium excretion was statistically significantly reduced from baseline (3565 mg/day) compared to at 12 weeks (3128 mg/day) in the intervention group (P = 0.004). Urinary sodium in the control group decreased slightly from baseline (3312 mg/day) to 12 weeks (3036 mg/day), but this change was not statistically significant (P = 0.267) (Fig 2).

10.1371/journal.pone.0311908.g002 The change of urine sodium excretion (Una). 10.1371/journal.pone.0311908.t002 The change of urine sodium excretion and blood pressure in both groups.
Intervention Control Difference in changes between groupP value$ Difference in changes between groupAdjusted P value#
0 week 12 weeks Δ change P valueΔ change 0 week 12 weeks Δ change P valueΔ change
Primary outcome
Urine Na, median (IQR) (mg/24h) 3565 (2783–4945) 3128 (2208–4163) -575 (-1541-552) 0.004* 3312 (2473–4405) 3036 (2300–4600) -299 (-1392-840) 0.267 0.194 0.117
Secondary outcome
SBP, mean ± SD (mmHg) 143.6 ± 13.4 130.1 ± 13.4 -13.5 ± 14.2 <0.001* 142.2 ± 12.2 132.7 ± 15.5 -9.5 ± 12.8 <0.001* 0.030* 0.021*
DBP, mean ± SD (mmHg) 82.1 ± 9.7 75.7 ± 8.8 -6.4 ± 8.7 <0.001* 81.4 ± 11.5 76.6 ± 9.8 -4.8 ± 8.4 <0.001* 0.164 0.212

$P value different between group

#P value by regression adjusted for clustering and baseline: age, sex, education, occupation, weight, height, body mass index and waist circumference

*P value <0.05, statistical significance

There was a reduction in systolic blood pressure 13.5 ± 14.2 mmHg in the intervention group and 9.5 ± 12.8 mmHg in the control group at 12 weeks, making the difference between groups of -4.0 mmHg which was statistically significant (P = 0.030). This remained true even after adjusting for clustering and baseline variables, p-value was 0.021. For the intra-group change, the systolic blood pressure significantly decreased from 143.6 ± 13.4 mmHg to 130.1 ± 13.4 mmHg in the intervention group (P<0.001) and from 142.2±12.2 mmHg to 132.7±15.5 mmHg in the control group (P<0.001). The diastolic blood pressure also significantly decreased from baseline of 82.1 ± 9.7 mmHg to 75.7 ± 8.8 mmHg at 12 weeks in the intervention group (P<0.001) and from 81.4 ± 11.5 mmHg to 76.6 ± 9.8 mmHg in the control group (P<0.001) (Fig 3). The difference in diastolic blood pressure reduction from baseline between the intervention group and control group was -1.6 mmHg at 12 weeks, but the difference was not statistically significant (P = 0.164). The intra-cluster correlation coefficients were 0.754 and 0.826 for systolic blood pressure and diastolic blood pressure respectively. Since the baseline body weight and BMI were statistically higher in the interventional group, we studied changes in these characteristics after 12 weeks of follow-up. There was no significant difference (P = 0.09) in the change in BMI from baseline between the two groups (BMI decreased by 0.03 and 0.23 kg/m2 in the intervention and control groups, respectively). Therefore, the noticeable changes in blood pressure were not attributable to weight reduction.

10.1371/journal.pone.0311908.g003 The change of blood pressure. The changes in knowledge, attitudes, and behaviors about salt intake

The changes in knowledge, attitude, and behavior regarding salt consumption after 12 weeks of the experiment are presented in Table 3. The behavior score showed improvement in intervention group and was significantly different between groups after 12 weeks (P = 0.035), with a mean difference of 1.27. However, there were no significant differences in the knowledge score (P = 0.204) or attitude score (P = 0.460).

10.1371/journal.pone.0311908.t003 The changes in knowledge, attitudes, and behaviors about salt intake.
Intervention Control Difference in changes between groupP value$ Difference in changes between groupAdjusted P value#
0 week 12 weeks Δ change P valueΔ change 0 week 12 weeks Δ change P valueΔ change
Knowledge mean ± SD (10) 7.77 ± 1.74 8.14 ± 1.34 0.38 ± 2.08 0.058 7.83 ± 1.65 7.86 ± 1.72 0.03 ± 1.99 0.885 0.204 0.234
Attitude mean ± SD (65) 45.65 ± 9.73 47.95 ± 7.41 2.30 ± 10.14 0.019* 44.20 ± 7.49 45.50 ± 6.56 1.30 ± 9.84 0.174 0.460 0.846
Behavior mean ± SD (42) 28.53 ± 4.75 30.59 ± 2.79 2.05 ± 5.21 <0.001* 29.09 ± 2.74 29.88 ± 2.45 0.79 ± 3.49 0.021* 0.035* 0.073

$P value different between group

#P value by regression adjusted for clustering and baseline: age, sex, education, occupation, weight, height, body mass index and waist circumference

*P value <0.05, statistical significance

 Discussion

This study evaluated the effects of a comprehensive approach, which included intensive dietary education, food reformulation, community management and the use of a salt meter, on patients with hypertension. The results indicated significant reductions in systolic blood pressure due to these interventions, but no significant effect was observed on diastolic blood pressure. Urine sodium excretion had a trend to decrease significantly in the intervention group. These findings suggest that the comprehensive approaches for sodium reduction intervention were effective in reducing urine sodium excretion, as well as improving behavior related to sodium reduction. There was no significant improvement in knowledge about sodium reduction, which suggests that additional educational efforts may be needed to improve the understanding of the importance of sodium reduction.

Several studies have demonstrated effective sodium reduction strategies in reducing blood pressure and improving cardiovascular outcomes. Based on data from a systematic review, it was found that 21 recent interventions were successful in reducing dietary sodium. Interventions that emphasize individual education, either alone or in combination with tools to estimate sodium intake, have demonstrated positive outcomes in reducing salt consumption [14]. Most studies have mainly focused on education-based interventions. We observed the trend in reduction of blood pressure and 24-hour urinary sodium excretion in the control group during follow-up clinic visit, indicating that standard health education is properly implemented in our study. However, reducing dietary sodium intake has been challenging due to a lack of awareness and high threshold in detecting saltiness. Long-term consumption of high sodium is associated with decreased sensitivity to salty taste and increased threshold for detecting saltiness [15, 16], which is a significant contributing factor that leads to an increased tendency for individuals to consume higher amounts of sodium.

Compared to other studies, Morikawa et al. [17] investigated the effect of salt reduction on blood pressure using an electronic sensor and cellular phone. They found a significant decrease in systolic blood pressure after the intervention period. Takada et al. [18] also examined the effects of self-monitoring of salt intake using a simple electrical device. The study found that the intervention group had a significant reduction in salt consumption and a decrease in blood pressure. Another study by Yokokawa et al. [19] in Thailand focused on a dietary intervention in diabetic and hypertensive adults with high cardiovascular risk, resulting in significant reduction in systolic blood pressure, as well as improvements in lipid profiles and glycemic control. Finally, our previous study, the SMAL-SALT study [13] implemented a salt reduction intervention among hypertensive patients attending an outpatient clinic through a combination of dietary education and salt meter usage. We also found significant reductions in systolic blood pressure and daily sodium intake. However, their study did not assess changes in knowledge, attitudes, and behaviors related to sodium reduction. This is consistent with the findings of the current study that found a significant reduction in blood pressure and improved dietary habits in the intervention group.

Overall, these studies support the effectiveness of salt reduction strategies in reducing blood pressure, and suggest that strategies such as self-monitoring, nutritional education, and dietary counseling can be effective in promoting salt reduction. The findings from this study may be applied to a larger target group to help implement community salt reduction policies in Thailand. In Finland and the United Kingdom, the governments have launched strategies of salt awareness, in collaboration with the industry, and have mandated salt labeling. In Finland, these strategies were successful and lead to a significant decrease in salt intake from 14 gram/day in 1972 to 9 gram/day in 2002, resulting in a 10 mmHg decline in blood pressure and a 75–80% reduction in cardiovascular mortality [20]. Similarly, sodium reduction strategy in the United Kingdom, starting in 2003, resulted in a 17% decrease in salt intake between 2008/2009 and 2016/2017 [21–23].

The strengths of this study is the study design which is a cluster randomized control trial performed in the community to compare effects of the interventions on reducing sodium excretion and blood pressure. There are some limitations such as it was a non-blinded study due to interventions that were unable to be masked. The findings of knowledge, attitude, and behavior related to dietary consumption in this study can be considered as exploratory outcomes. We did not consider lifestyle changes (e.g. exercise) and baseline anti-hypertensive medications. This is due to the fact that in the rural primary healthcare setting where this study was done, there is a limited list of first-line medications for high blood pressure (thiazide diuretics, calcium channel blockers and angiotensin-converting enzyme inhibitors). Sodium-glucose cotransporters-2 inhibitors are not available in this setting. In addition, there were no reports of any symptoms related to hypertensive complications, nor any adjustment of medications in our patients. Furthermore, the results of this study may have limited generalizability as the local research team was selected from a group of talented and enthusiastic staff involved in the salt reduction campaign and the study was conducted in selected villages.

 Conclusions

The combined intervention of intensive dietary education, food reformulation, environmental changes in the community, and salt meter utilization significantly decreased systolic blood pressure and showed a trend towards reduced urine sodium excretion. These findings suggest that implementing a comprehensive approach to sodium reduction in patients with hypertension may be effective in controlling salt intake and managing blood pressure in the community.

 Supporting information This is the CONSORT-2010-checklist of the project.

(DOC)

 This is the questionnaire on the knowledge, attitude, and behavior, related to dietary consumption.

In Thai.

(PDF)

 This is the questionnaire on the knowledge, attitude, and behavior, related to dietary consumption.

In English.

(PDF)

 This is the protocol of study project in Thai.

(PDF)

 This is the protocol of study project in English.

(PDF)

 This is the data correction file.

(XLSX)

We would like to thank Mrs. Premthip Tiathaweekiat, Miss Nichanan Archtanyakam, Miss Nanara Padasittiphum, Mrs. Manawika Kulnee, Miss Apatsara Jantarat, Mrs. Kanokwan Pratheep, Mr. Tanakrit Junjajan, and Miss Kritaron Lao-in, the Uthaithani team for technical support and data collection.

 References WHO Guidelines Approved by the Guidelines Review Committee. Guideline: Sodium Intake for Adults and Children. Geneva: World Health Organization Afshin A, Sur PJ, Fay KA, Cornaby L, Ferrara G, Salama JS, et al. Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2019;393(10184):1958–72. doi: 10.1016/S0140-6736(19)30041-8 30954305 Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. Bmj. 1988;297(6644):319–28. Filippini T, Malavolti M, Whelton PK, Naska A, Orsini N, Vinceti M. Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies. Circulation. 2021;143(16):1542–67. doi: 10.1161/CIRCULATIONAHA.120.050371 33586450 Mente A, O’Donnell MJ, Rangarajan S, McQueen MJ, Poirier P, Wielgosz A, et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med. 2014;371(7):601–11. doi: 10.1056/NEJMoa1311989 25119606 Whelton PK, He J. Health effects of sodium and potassium in humans. Curr Opin Lipidol. 2014;25(1):75–9. doi: 10.1097/MOL.0000000000000033 24345983 He FJ, Tan M, Ma Y, MacGregor GA. Salt Reduction to Prevent Hypertension and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(6):632–47. doi: 10.1016/j.jacc.2019.11.055 32057379 He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. Bmj. 2013;346:f1325. doi: 10.1136/bmj.f1325 23558162 He FJ, Macgregor GA. Salt intake, plasma sodium, and worldwide salt reduction. Ann Med. 2012;44 Suppl 1:S127-37. doi: 10.3109/07853890.2012.660495 22713141 Chailimpamontree W, Kantachuvesiri S, Aekplakorn W, Lappichetpaiboon R, Sripaiboonkij Thokanit N, Vathesatogkit P, et al. Estimated dietary sodium intake in Thailand: A nationwide population survey with 24-hour urine collections. J Clin Hypertens (Greenwich). 2021;23(4):744–54. doi: 10.1111/jch.14147 33420751 Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6): 1269–1324. Muangkae A, Perdpern I, Pongtong J, Putthawong K. Behavior modification at risk of chronic non-communicable diseases in relation to consumption of salty food using the community as the base in the upper northern region 2020. Chiangrai Medical Journal. 2023;1:107–21. Wiriyatanakorn S, Mukdadilok A, Kantachuvesiri S, Mekhora C, Yingchoncharoen T. Impact of self-monitoring of salt intake by salt meter in hypertensive patients: A randomized controlled trial (SMAL-SALT). J Clin Hypertens (Greenwich). 2021;23(10):1852–61. doi: 10.1111/jch.14344 34510703 Silva-Santos T, Moreira P, Rodrigues M, Padrão P, Pinho O, Norton P, et al. Interventions That Successfully Reduced Adults Salt Intake-A Systematic Review. Nutrients. 2021;14(1). doi: 10.3390/nu14010006 35010883 Öner C, Dilan Turan R, Telatar B, Yeşildağ Ş, Hergün Ş, Elmacıoğlu F. A pilot study on salt taste sensitivity threshold in Turkish young adults. Anatol J Cardiol. 2016;16(9):731–2. doi: 10.14744/AnatolJCardiol.2016.7257 27609439 Azinge EC, Sofola OA, Silva BO. Relationship between salt intake, salt-taste threshold and blood pressure in Nigerians. West Afr J Med. 2011;30(5):373–6. 22752827 Morikawa N, Yamasue K, Tochikubo O, Mizushima S. Effect of salt reduction intervention program using an electronic salt sensor and cellular phone on blood pressure among hypertensive workers. Clin Exp Hypertens. 2011;33(4):216–22. doi: 10.3109/10641963.2011.583966 21699447 Takada T, Imamoto M, Sasaki S, Azuma T, Miyashita J, Hayashi M, et al. Effects of self-monitoring of daily salt intake estimated by a simple electrical device for salt reduction: a cluster randomized trial. Hypertension Research. 2018;41(7):524–30. doi: 10.1038/s41440-018-0046-0 29695772 Yokokawa H, Yuasa M, Nedsuwan S, Moolphate S, Fukuda H, Kitajima T, et al. An impact of dietary intervention on blood pressures among diabetic and/or hypertensive patients with high cardiovascular disorders risk in northern Thailand by cluster randomized trial. J Gen Fam Med. 2021;22(1):28–37. doi: 10.1002/jgf2.379 33457153 Karppanen H, Mervaala E. Sodium Intake and Hypertension. Progress in Cardiovascular Diseases. 2006;49(2):59–75. doi: 10.1016/j.pcad.2006.07.001 17046432 He FJ, Pombo-Rodrigues S, MacGregor GA. Salt reduction in England from 2003 to 2011: its relationship to blood pressure, stroke and ischaemic heart disease mortality. BMJ Open. 2014;4(4):e004549. doi: 10.1136/bmjopen-2013-004549 24732242 Gressier M, Sassi F, Frost G. Contribution of reformulation, product renewal, and changes in consumer behavior to the reduction of salt intakes in the UK population between 2008/2009 and 2016/2017. Am J Clin Nutr. 2021;114(3):1092–9. doi: 10.1093/ajcn/nqab130 33963735 He FJ, Brinsden HC, MacGregor GA. Salt reduction in the United Kingdom: a successful experiment in public health. J Hum Hypertens. 2014;28(6):345–52. doi: 10.1038/jhh.2013.105 24172290 10.1371/journal.pone.0311908.r001 Decision Letter 0 Jain Yogesh Kumar Academic Editor 2024 Yogesh Kumar Jain This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 0

22 Apr 2024

PONE-D-24-07382Community-based intervention for monitoring of salt intake in hypertensive patients: A cluster randomized controlled trialPLOS ONE

Dear Dr. Kantachuvesiri,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

The manuscript has received an overall positive feedback, but would need refinement based on the reviewers suggestions. Kindly re-submit for further consideration.

==============================

Please submit your revised manuscript by Jun 06 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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PLOS ONE

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Additional Editor Comments:

The manuscript has received an overall positive feedback, but would need refinement based on the reviewers suggestions. Kindly resubmit for further consideration.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: No

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript is quite well written. However, the manuscript could be refined.

Comments

More information on the randomization method and process, and who performed it is to be provided.

Line 106, more information on the standard questionnaire on their knowledge, attitude, and behaviour is to be provided e.g. reliability and validation information of the questionnaire in the context of local setting.

For sample size calculation, the formula for the sample size and the value corresponding to each item is to be displayed.

Line 131-132, for Fisher’s exact test, 1 or 2-tailed test and Line 132, the specific name of the t-test to be stated.

Line 133, comparison between groups whether at certain time point(s) between the groups or the differences in pre and post-intervention between the two groups is to be stated.

Line 134, the statement ‘The change of blood pressure was performed with linear mixed-effects model’ and Line 135 with the statement ‘In addition, the changes of variables between the group and associated test of effect were estimated by regression’ requires more information. A statement on fulfilment of LMM assumptions is to be stated.

Line 134, as the change of blood pressure was measured at baseline, 4 weeks, 8 weeks and 12 weeks. Depending on the specific aim(s) of the study, the number of comparisons being made, the correlation structure of the data, and the balance between type I and type II errors, any adjustment to the p-value is to be clearly stated.

Line 136, the complete name of the regression test is to be stated.

The accepted level of statistical significance and whether 1 or 2 tailed p value is to be stated.

Intent to treat or per protocol analysis; missing data (if any) and method of handling missing data is to stated.

Table 1, Table 2 and Table 3, all statistical tests are to be denoted in the table footnote. For variables ‘other underlying diseases’ and ’24-hour urine’, the figures are to be placed in the same row with their respective category.

Table 2, effect size indices and 95% CI could be presented. The p-value in the change column is to be removed and placed in a separate column of each respective group. Presentation of p-value minus the symbol = e.g. P 0.004 is to be avoided. Likewise, with Table 3.

Ensure that all the information reported in the CONSORT checklist is presented or clearly presented in the manuscript.

Reviewer #2: Dear authors,

Congratulations for conducting and reporting the study. This study determines the effectiveness of a combined intervention on reducing salt intake and blood pressure relative to health education. The manuscript is well-written in standard English with sufficient data presentation, analysis, and discussion. The manuscript fulfills the stated aims and meets the standard for publication.

Strengths of the study

Authors have clearly established the research gaps and objectives. The chosen study design (cluster-randomised trial) is suitable to meet the study objectives. Data has been adequately presented and interpretated. Discussion is balanced and conclusion is based on the results and analysis.

Weaknesses of the study

Method:

Line 85: definition of hypertension is misleading. Current statement is not correct and citation is missing.

Line 91: Please provide details when clusters were randomised (e.g before or after the participants were recruited) and methods for randomisation of participants.

Line 87 and 88: The expression "During the conduction of the trial, participants were not allowed to adjust their antihypertensive or diuretic medication" is misleading. Is it ethical not to allow participants to alter the drug?

Line 105: Authors did not register the "knowledge, attitude, and behavior related to dietary consumption" related outcome in the trial registry. This can be considered as exploratory outcomes only.

Line 109 to 116: Please provide the details of intervention (e.g duration and sessions of health education), so that the intervention could be replicated.

Results:

Table 1: *is missing in the table. What indicates * for.

Table 2: Please report intra-cluster correlation coefficients for the reported outcomes. These are important for future studies to estimate power and meta-analyse.

Discussion:

Line 217: "Furthermore, we observed the trend in reduction of blood pressure and 24-hour urinary sodium excretion in the control group which may be due to patient education or unknown intervention during follow-up clinic visit". It is not the limitation of the study. Instead, This is the indication that standard health education is properly implemented. Therefore, this could be discussed separately.

Line 219: The generalisability is limited as the study was conducted in selected villages.

There are additional limitations. One limitation is not considering important lifestyle changes (e.g exercise). Authors did not report baseline data on history of current anti-hypertensive medication, which either could be adjusted in the analysis or acknowledged in the limitation.

It would be easier to follow the structure when strength and limitations are in the last sentence of discussion section.

Limitations:

Language:

There are a few errors in English language: e.g

Line 198: Long term is Long-term

Incorporating these comments will improve the quality of the manuscript.

**********

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Reviewer #1: No

Reviewer #2: Yes: Mahesh Kumar Khanal

**********

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 10.1371/journal.pone.0311908.r002 Author response to Decision Letter 0 Submission Version 1

5 Jun 2024

Response to reviewers

Reviewer #1: The manuscript is quite well written. However, the manuscript could be refined.

Comments

More information on the randomization method and process, and who performed it is to be provided. – completed, lines 96–102 of the tracked changes version .

Ans. Each health center was responsible for 10-12 villages. We used a random number generator, to assign a random number (1, 2) to each village (cluster). The villages assigned the number 1 were the intervention group, and the villages assigned the number 2 were the control group. A total of 6 clusters were randomly allocated to the intervention group and another 6 clusters to the control group. A total of 20 patients meeting the eligible criteria were randomly recruited, using the random number generator, in each cluster. Informed consent was obtained from all participants. (Fig 1)

Line 106, more information on the standard questionnaire on their knowledge, attitude, and behaviour is to be provided e.g. reliability and validation information of the questionnaire in the context of local setting. – completed, lines 109-112.

Ans. The questionnaire was developed according to the local context and its content validity was assessed by 3 experts. It was tested for reliability, with the instrument achieving a Cronbach's alpha coefficient of 0.79 [12].

For sample size calculation, the formula for the sample size and the value corresponding to each item is to be displayed. – completed, lines 135-137.

Ans.

n= ((a+b)^(2 ) (〖SD〗_i^2+〖SD〗_c^2 ))/((m_i-m_c )^2 )

a= Z alpha=1.96, b= Z1-beta=1.28, SD= standard deviation of BP for intervention and control, mi-mc =mean changes of BP between intervention and control.

Line 131-132, for Fisher’s exact test, 1 or 2-tailed test and Line 132, the specific name of the t-test to be stated. – completed, lines 139-141.

Ans. Categorical variables were analyzed using Fisher's exact test when expected values were less than 5, while continuous variables were analyzed using the student’s t-test with 2-tailed test.

Line 133, comparison between groups whether at certain time point(s) between the groups or the differences in pre and post-intervention between the two groups is to be stated. – completed, lines 141-143 .

Ans. The primary outcomes were evaluated using the Wilcoxon rank-sum test, while the Wilcoxon signed-rank test was used to compare urine sodium excretion within group between pre and post intervention and between two groups.

Line 134, the statement ‘The change of blood pressure was performed with linear mixed-effects model’ and Line 135 with the statement ‘In addition, the changes of variables between the group and associated test of effect were estimated by regression’ requires more information. A statement on fulfilment of LMM assumptions is to be stated. – completed, lines 144-146.

Ans. The change of blood pressure was performed with linear mixed-effects model (LMM) since the study measured blood pressure (BP) multiple times on each participant before and after intervention. LMMs account for the correlation between these repeated measures within each participant. We used an unstructured correlation structure.

Line 134, as the change of blood pressure was measured at baseline, 4 weeks, 8 weeks and 12 weeks. Depending on the specific aim(s) of the study, the number of comparisons being made, the correlation structure of the data, and the balance between type I and type II errors, any adjustment to the p-value is to be clearly stated. – completed, line 146.

Ans. We used an unstructured correlation structure.

Line 136, the complete name of the regression test is to be stated. completed, line 144.

Ans. The change of blood pressure was performed with linear mixed-effects model (LMM) since the study measured blood pressure (BP) multiple times on each participant before and after intervention.

The accepted level of statistical significance and whether 1 or 2 tailed p value is to be stated. -completed, lines 140-141 and 151-152.

Ans. The continuous variables were analyzed using the student’s t-test with 2-tailed test.

Statistical significance was set at P-value <0.05.

Intent to treat or per protocol analysis; missing data (if any) and method of handling missing data is to stated. -completed, line 143-144.

Ans. We used an intention to treat analysis. Participants with incomplete data were excluded in the analysis.

Table 1, Table 2 and Table 3, all statistical tests are to be denoted in the table footnote. For variables ‘other underlying diseases’ and ’24-hour urine’, the figures are to be placed in the same row with their respective category.

Ans. We added P value and the figures. All statistical tests are to be denoted in the table footnote in Table 1,2 and 3 as suggested

Table 2, effect size indices and 95% CI could be presented. The p-value in the change column is to be removed and placed in a separate column of each respective group. Presentation of p-value minus the symbol = e.g. P 0.004 is to be avoided. Likewise, with Table 3. -completed, in Table 1,2 and 3.

Ensure that all the information reported in the CONSORT checklist is presented or clearly presented in the manuscript. -Completed as suggested in the manuscript.

Reviewer #2: Dear authors,

Congratulations for conducting and reporting the study. This study determines the effectiveness of a combined intervention on reducing salt intake and blood pressure relative to health education. The manuscript is well-written in standard English with sufficient data presentation, analysis, and discussion. The manuscript fulfills the stated aims and meets the standard for publication.

Strengths of the study

Authors have clearly established the research gaps and objectives. The chosen study design (cluster-randomised trial) is suitable to meet the study objectives. Data has been adequately presented and interpretated. Discussion is balanced and conclusion is based on the results and analysis.

Weaknesses of the study

Method:

Line 85: definition of hypertension is misleading. Current statement is not correct and citation is missing. -completed, line 85 of the tracked changes version.

Ans. The participants included in this study were aged between 18-70 years and had a diagnosis of hypertension (systolic blood pressure ≥130 or diastolic blood pressure ≥ 80 mmHg)[11].

Line 91: Please provide details when clusters were randomised (e.g before or after the participants were recruited) and methods for randomisation of participants. -completed, line96-102.

Ans. Each health center was responsible for 10-12 villages. We used a random number generator, to assign a random number (1, 2) to each village (cluster). The villages assigned the number 1 were the intervention group, and the villages assigned the number 2 were the control group. A total of 6 clusters were randomly allocated to the intervention group and another 6 clusters to the control group. A total of 20 patients meeting the eligible criteria were randomly recruited, using the random number generator, in each cluster. Informed consent was obtained from all participants. (Fig 1)

Line 87 and 88: The expression "During the conduction of the trial, participants were not allowed to adjust their antihypertensive or diuretic medication" is misleading. Is it ethical not to allow participants to alter the drug? -completed, lines 87-90.

Ans. If participants had systolic blood pressure exceeding 180 mmHg or presented with hypertensive emergencies, they were excluded from the study.

Line 105: Authors did not register the "knowledge, attitude, and behavior related to dietary consumption" related outcome in the trial registry. This can be considered as exploratory outcomes only.

Ans. We agree and added in the discussion lines 242-244.

Line 109 to 116: Please provide the details of intervention (e.g duration and sessions of health education), so that the intervention could be replicated. -completed, lines 115-116.

Ans. First, intensive dietary education, participants received education from nurses and dietitians about high sodium intake, sources of sodium, and nutritional ingredients for 2 hours on day 0 and for 1 hour at 4 and 8 weeks.

Results:

Table 1: *is missing in the table. What indicates * for.

Ans. We added * and P value in the table and all statistical tests are to be denoted in the table footnote in Table 1,2 and 3 as suggested

Table 2: Please report intra-cluster correlation coefficients for the reported outcomes. These are important for future studies to estimate power and meta-analyse. -completed, lines 189-190.

Ans. The intra-cluster correlation coefficients were 0.754 and 0.826 for systolic blood pressure and diastolic blood pressure respectively.

Discussion:

Line 217: "Furthermore, we observed the trend in reduction of blood pressure and 24-hour urinary sodium excretion in the control group which may be due to patient education or unknown intervention during follow-up clinic visit". It is not the limitation of the study. Instead, This is the indication that standard health education is properly implemented. Therefore, this could be discussed separately.

Ans. We agree and edited in the discussion as suggested on lines 212-214

Line 219: The generalisability is limited as the study was conducted in selected villages. -completed, line 248.

There are additional limitations. One limitation is not considering important lifestyle changes (e.g exercise). Authors did not report baseline data on history of current anti-hypertensive medication, which either could be adjusted in the analysis or acknowledged in the limitation. -completed, lines 244-246.

It would be easier to follow the structure when strength and limitations are in the last sentence of discussion section.

Ans: We agree and edited in the discussion as suggested on lines 240-248.

Limitations:

Language:

There are a few errors in English language: e.g

Line 198: Long term is Long-term -completed, line 215.

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

We have checked and ensured our manuscript meets PLOS ONE’s requirements.

2. We note that you have selected “Clinical Trial” as your article type. PLOS ONE requires that all clinical trials are registered in an appropriate registry (the WHO list of approved registries is at https://www.who.int/clinical-trials-registry-platform/network/primary-registries" https://www.who.int/clinical-trials-registry-platform/network/primary-registries and more information on trial registration is at http://www.icmje.org/about-icmje/faqs/clinical-trials-registration/).

Please state the name of the registry and the registration number (e.g. ISRCTN or ClinicalTrials.gov) in the submission data and on the title page of your manuscript. completed, line 15-16.

a) Please provide the complete date range for participant recruitment and follow-up in the methods section of your manuscript. completed, line 93.

b) If you have not yet registered your trial in an appropriate registry, we now require you to do so and will need confirmation of the trial registry number before we can pass your paper to the next stage of review. Please include in the Methods section of your paper your reasons for not registering this study before enrolment of participants started. Please confirm that all related trials are registered by stating: “The authors confirm that all ongoing and related trials for this drug/intervention are registered”.

Please see http://journals.plos.org/plosone/s/submission-guidelines#loc-clinical-trials for our policies on clinical trials.

3. Thank you for stating the following financial disclosure:

"This study was financially supported by the Thai Health Promotion Foundation No. 64-00255-0002 and World Health Organization (WHO) office, Thailand, registration 2021/1159185-0 "

Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. -Completed in covering letter.

4. We note that the original protocol that you have uploaded as a Supporting Information file contains an institutional logo. As this logo is likely copyrighted, we ask that you please remove it from this file and upload an updated version upon resubmission. -Completed and new file attached

Submitted filename: Response to reviewers.docx

 10.1371/journal.pone.0311908.r003 Decision Letter 1 Gao Peng Academic Editor 2024 Peng Gao This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 1

21 Jun 2024

PONE-D-24-07382R1Community-based intervention for monitoring of salt intake in hypertensive patients: A cluster randomized controlled trialPLOS ONE

Dear Dr. Kantachuvesiri,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 05 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Peng Gao, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: Dear authors,

Thank you for addressing my previous comments.

I only have a few minor corrections. Please make the writing of p value consistent, either p or P. All tables contain the redundant letter P, column head with P value is enough. To improve reading, all the table titles should be just before each table. These corrections can be made even during production phase.

Congratulations!

Kind regards,

Reviewer #3: The authors have adequately addressed most of the comments raised in a previous round of review. This manuscript needs further improvement.

1.The positioning of the modifications made in the author's response does not match the actual situation, resulting in reading difficulties.

2. It would be preferable to use a three-line table format in the assay

3. The patients recruited exhibited a significant age range, with the youngest being only 18 years old. But the exclusion criteria do not include secondary hypertension, such as primary aldosteronism. Salt intake may play a more significant role in this condition.

4. The author provided detailed imformation about the randomization method and process. Line 207,“240 participants were enrolled from 6 clusters/group”, 12 clusters might be an accurate representation according to my understanding.

5.In the discussion section, the author noted that there was no adjustment of medication in patients. It is puzzling that the blood pressure in the control group still showed a significant decline.

6.As mentioned before, the presentation of p-value should not minus the symbol = e.g. P 0.004.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

 10.1371/journal.pone.0311908.r004 Author response to Decision Letter 1 Submission Version 2

15 Jul 2024

Reviewer #2: I only have a few minor corrections. Please make the writing of p value consistent, either p or P. All tables contain the redundant letter P, column head with P value is enough. To improve reading, all the table titles should be just before each table. These corrections can be made even during production phase.

Ans. We used P value consistently in the manuscript. We deleted P value in all the tables except column head and put the titles before each table as suggested.

Reviewer #3: The authors have adequately addressed most of the comments raised in a previous round of review. This manuscript needs further improvement.

1. The positioning of the modifications made in the author's response does not match the actual situation, resulting in reading difficulties.

Ans. We revised the manuscript which the positioning of modification in the author’s response to match the actual situation as suggested.

2. It would be preferable to use a three-line table format in the assay

Ans. We changed all tables to a three-line table format as suggested.

3. The patients recruited exhibited a significant age range, with the youngest being only 18 years old. But the exclusion criteria do not include secondary hypertension, such as primary aldosteronism. Salt intake may play a more significant role in this condition.

Ans. We recruited the patients with no identifiable causes of hypertension and randomized them so that the underlying diseases were comparable. Furthermore, most of the patients were middle-aged and elderly patients, with a mean age of 60 + 7.5 (range 26-70) years old in intervention group and 60.2 + 7.5 (range 36-70) in control group, which is an uncommon age group for primary aldosteronism.

4. The author provided detailed information about the randomization method and process. Line 207,“240 participants were enrolled from 6 clusters/group”, 12 clusters might be an accurate representation according to my understanding.

Ans. Participants were recruited from twelve clusters (villages) in six healthcare centers. (line 122) A total of 6 clusters were randomly allocated to the intervention group and another 6 clusters to the control group. (Line 129-131)

5.In the discussion section, the author noted that there was no adjustment of medication in patients. It is puzzling that the blood pressure in the control group still showed a significant decline.

Ans. We observed the trend in reduction of blood pressure and 24-hour urinary sodium excretion in the control group during follow-up clinic visit, indicating that standard health education was properly implemented in our study and may contribute to improvement in blood pressure control. (Line 297-300)

6.As mentioned before, the presentation of p-value should not minus the symbol = e.g. P 0.004.

Ans. We made change of P value as suggested.

Submitted filename: Response to reviewers.docx

 10.1371/journal.pone.0311908.r005 Decision Letter 2 Gao Peng Academic Editor 2024 Peng Gao This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 2

26 Aug 2024

PONE-D-24-07382R2Community-based intervention for monitoring of salt intake in hypertensive patients: A cluster randomized controlled trialPLOS ONE

Dear Dr. Kantachuvesiri,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Peng Gao, Ph.D.

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: (No Response)

Reviewer #4: In this manuscript, the authors explored the effects of salt intake monitoring in urine sodium excretion and blood pressure. However, there are some concerns need to be addressed.

1. Sine the baseline body weight and BMI were statistically higher in interventional group, the changes of these characteristics after follow-up should be provided and whether the changes were correlated with improver BP should be explored.

2. The details of medicine should be provided, especially SGLT2i.

3. The results should be presented with brief titles.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

 10.1371/journal.pone.0311908.r006 Author response to Decision Letter 2 Submission Version 3

19 Sep 2024

We response to reviewers’ comments below.

Reviewer #4: In this manuscript, the authors explored the effects of salt intake monitoring in urine sodium excretion and blood pressure. However, there are some concerns need to be addressed.

1. Since the baseline body weight and BMI were statistically higher in interventional group, the changes of these characteristics after follow-up should be provided and whether the changes were correlated with improver BP should be explored.

Answer. Since the baseline body weight and BMI were statistically higher in the interventional group, we studied changes in these characteristics after 12 weeks of follow-up. There was no significant difference (P=0.09) in the change in BMI from baseline between the two groups (BMI decreased by 0.03 and 0.23 kg/m2 in the intervention and control groups, respectively). Therefore, the noticeable changes in blood pressure were not attributable to weight reduction. (Lines 190-194 in revised manuscript with track changes)

2. The details of medicine should be provided, especially SGLT2i.

Answer. We did not consider lifestyle changes (e.g. exercise) and baseline anti-hypertensive medications. This is due to the fact that in the rural primary healthcare setting where this study was done, there is a limited list of first-line medications for high blood pressure (thiazide diuretics, calcium channel blockers and angiotensin-converting enzyme inhibitors). Sodium-glucose cotransporters-2 inhibitors are not available in this setting. In addition, there were no reports of any symptoms related to hypertensive complications, nor any adjustment of medications in our patients (Discussion on limitation of the study, Lines 249-254.)

3. The results should be presented with brief titles.

Answer. We put brief titles in the results as suggested.

1. In the online submission form you indicate that your data is not available for proprietary reasons and have provided a contact point for accessing this data. Please note that your current contact point is a co-author on this manuscript. According to our Data Policy, the contact point must not be an author on the manuscript and must be an institutional contact, ideally not an individual. Please revise your data statement to a non-author institutional point of contact, such as a data access or ethics committee, and send this to us via return email. Please also include contact information for the third party organization, and please include the full citation of where the data can be found.

Answer We have added the all relevant data in the Supporting Information file.

Submitted filename: Response to reviewers.docx

 10.1371/journal.pone.0311908.r007 Decision Letter 3 Gao Peng Academic Editor 2024 Peng Gao This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 3

27 Sep 2024

Community-based intervention for monitoring of salt intake in hypertensive patients: A cluster randomized controlled trial

PONE-D-24-07382R3

Dear Dr. Kantachuvesiri,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Peng Gao, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

 10.1371/journal.pone.0311908.r008 Acceptance letter Gao Peng Academic Editor 2024 Peng Gao This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

2 Oct 2024

PONE-D-24-07382R3

PLOS ONE

Dear Dr. Kantachuvesiri,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

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on behalf of

Professor Peng Gao

Academic Editor

PLOS ONE