Effect of Salt Substitution on Cardiovascular Events and Death.

Journal Article (Multicenter Study;Journal Article)

Background

Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain.

Methods

We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia.

Results

A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76).

Conclusions

Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).

Full Text

Duke Authors

Cited Authors

  • Neal, B; Wu, Y; Feng, X; Zhang, R; Zhang, Y; Shi, J; Zhang, J; Tian, M; Huang, L; Li, Z; Yu, Y; Zhao, Y; Zhou, B; Sun, J; Liu, Y; Yin, X; Hao, Z; Yu, J; Li, K-C; Zhang, X; Duan, P; Wang, F; Ma, B; Shi, W; Di Tanna, GL; Stepien, S; Shan, S; Pearson, S-A; Li, N; Yan, LL; Labarthe, D; Elliott, P

Published Date

  • September 2021

Published In

Volume / Issue

  • 385 / 12

Start / End Page

  • 1067 - 1077

PubMed ID

  • 34459569

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

International Standard Serial Number (ISSN)

  • 0028-4793

Digital Object Identifier (DOI)

  • 10.1056/nejmoa2105675

Language

  • eng