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Effect of salt substitution on community-wide blood pressure and hypertension incidence

Nature Medicine volume 26, pages 374–378 (2020)Cite this article

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Abstract

Replacement of regular salt with potassium-enriched substitutes reduces blood pressure in controlled situations, mainly among people with hypertension. We report on a population-wide implementation of this strategy in a stepped-wedge cluster randomized trial (NCT01960972). The regular salt in enrolled households was retrieved and replaced, free of charge, with a combination of 75% NaCl and 25% KCl. A total of 2,376 participants were enrolled in 6 villages in Tumbes, Peru. The fully adjusted intention-to-treat analysis showed an average reduction of 1.29 mm Hg (95% confidence interval (95% CI) (−2.17, −0.41)) in systolic and 0.76 mm Hg (95% CI (−1.39, −0.13)) in diastolic blood pressure. Among participants without hypertension at baseline, in the time- and cluster-adjusted model, the use of the salt substitute was associated with a 51% (95% CI (29%, 66%)) reduced risk of developing hypertension compared with the control group. In 24-h urine samples, there was no evidence of differences in sodium levels (mean difference 0.01; 95% CI (0.25, −0.23)), but potassium levels were higher at the end of the study than at baseline (mean difference 0.63; 95% CI (0.78, 0.47)). Our results support a case for implementing a pragmatic, population-wide, salt-substitution strategy for reducing blood pressure and hypertension incidence.

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Fig. 1: Flowchart of participants in the stepped-wedge trial.
Fig. 2: Trends in mean SBP and DBP.
Fig. 3: Structure and time framework of the stepped-wedge, cluster, randomized controlled trial.

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Data availability

Anonymized clinical and anthropometric data are available on request, subject to an internal review by J.J.M., R.H.G. and A.B.-O. to ensure that the participants’ anonymity and confidentiality are protected, with completion of a data-sharing agreement, and in accordance with the Universidad Peruana Cayetano Heredia and Johns Hopkins University’s institutional review boards and institutional guidelines. Material requests, that is marketing campaign information or economics data requests, will be considered based on a proposal review, and completion of a material transfer agreement and/or a data use agreement. Please submit requests for participant-related clinical and other data to A.B.-O. (Antonio.Bernabe@upch.pe), copying to J.J.M. (Jaime.Miranda@upch.pe).

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Acknowledgements

This study was supported by the National Heart, Lung and Blood Institute (Project 5 U01 HL114180-01), under the Global Alliance for Chronic Diseases hypertension program. A.B.-O. was supported by a Wellcome Trust Research Training Fellowship in Public Health and Tropical Medicine (grant no. 103994/Z/14/Z). V.G.S.y.R. was funded by the Dirección de Gestión de la Investigación at the Pontifica Universidad Católica del Perú (grant no. DGI-2017-496).

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Authors and Affiliations

  1. CRONICAS Centre of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru

    Antonio Bernabe-Ortiz, Vilarmina Ponce-Lucero, María K. Cárdenas, Rodrigo M. Carrillo-Larco, Francisco Diez-Canseco, M. Amalia Pesantes & J. Jaime Miranda

  2. Department of Science, Pontifica Universidad Católica del Perú, Lima, Peru

    Víctor G. Sal y Rosas

  3. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    Rodrigo M. Carrillo-Larco

  4. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Katherine A. Sacksteder & Robert H. Gilman

  5. Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru

    J. Jaime Miranda

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Contributions

A.B.-O. and J.J.M. drafted the first version of the manuscript. R.M.C.-L. provided input to this version of the manuscript. A.B.-O., R.H.G., K.A.S. and J.J.M. conceived and designed the overall study. V.G.S.y.R. and A.B.-O. developed the statistical analysis plan and conducted the statistical analysis. V.P.-L. led the social marketing campaign. M.K.C. designed the strategy for the cost-effectiveness analysis. F.D.-C. and M.A.P. conducted qualitative work during the intervention as part of a process evaluation. All the authors contributed to the revision of the manuscript for important content and gave their final approval of the version submitted for publication.

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Correspondence to J. Jaime Miranda.

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Peer review information Jennifer Sargent was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Trends in mean SBP and their respective 95% confidence intervals by village and intervention period.

Blue symbols and lines indicate measurements and time before institution of the study intervention, and brown symbols and lines represent the intervention time periods. Time periods are 5-month analysis periods occurring before the initiation of the intervention in each wave.

Extended Data Fig. 2 Trends in mean DBP and their respective 95% confidence intervals by village and intervention period.

Blue symbols and lines indicate measurements and time before institution of the study intervention, and brown symbols and lines represent the intervention time periods. Time periods are 5-month analysis periods occurring before the initiation of the intervention in each wave.

Extended Data Fig. 3 Cumulative probability of developing hypertension in the intervention and control group during the duration of the study.

Probability of developing hypertension in the intervention and control groups.

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Supplementary Tables 1–4 and Statistical analysis

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Bernabe-Ortiz, A., Sal y Rosas, V.G., Ponce-Lucero, V. et al. Effect of salt substitution on community-wide blood pressure and hypertension incidence. Nat Med 26, 374–378 (2020). https://doi.org/10.1038/s41591-020-0754-2

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