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Original research
Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis
  1. Xuejun Yin1,
  2. Anthony Rodgers1,
  3. Adam Perkovic2,
  4. Liping Huang1,
  5. Ka-Chun Li1,
  6. Jie Yu1,
  7. Yangfeng Wu3,4,
  8. J H Y Wu1,
  9. Matti Marklund1,5,6,
  10. Mark D Huffman1,7,
  11. J Jaime Miranda1,8,9,
  12. Gian Luca Di Tanna1,
  13. Darwin Labarthe10,
  14. Paul Elliott11,
  15. Maoyi Tian1,12,
  16. Bruce Neal1,11
  1. 1The George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia
  2. 2School of Health Science, The University of Newcastle, Newcastle, New South Wales, Australia
  3. 3Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China
  4. 4Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
  5. 5Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
  6. 6Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
  7. 7Cardiovascular Division and Global Health Center, Washington University in St. Louis, St. Louis, Missouri, USA
  8. 8CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru
  9. 9Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
  10. 10Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
  11. 11School of Public Health, Imperial College of Science Technology and Medicine, London, UK
  12. 12School of Public Health, Harbin Medical University, Harbin, China
  1. Correspondence to Dr Maoyi Tian, School of Public Health, Harbin Medical University, Harbin, China; maoyi.tian{at}hrbmu.edu.cn

Abstract

Objectives The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.

Methods We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.

Results There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was −4.61 mm Hg (95% CI −6.07 to −3.14) and of diastolic blood pressure (DBP) was −1.61 mm Hg (95% CI −2.42 to −0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a −1.53 mm Hg (95% CI −3.02 to −0.03, p=0.045) greater reduction in SBP and a −0.95 mm Hg (95% CI −1.78 to −0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).

Conclusions The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.

Trial registration number CRD42020161077.

  • meta-analysis
  • hypertension
  • stroke

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Twitter @drbenzigerheart, @MaoyiT

  • Contributors XY drafted the paper and ran the search. XY, MT and BN developed the study concept and design. XY and KL screened articles for eligibility. XY and AP extracted data and assessed the risk of bias. AD and JY checked the accuracy of the data extraction. XY and LH conducted the data analysis. GLDT validated the data analysis. YW, JHYW, MM, MDH, JJM, DL PE, MT and BN contributed to the interpretation of results. All authors edited and revised the manuscript. BN is the guarantor who is responsible for the overall content, had access to the data and controlled the decision to publish.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.