Effect of Salt Substitution on Cardiovascular Events and Death

Abstract

BACKGROUNDSalt 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. METHODSWe 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. RESULTSA 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). CONCLUSIONSAmong 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.

Core Strategies to Increase the Uptake and Use of Potassium-Enriched Low-Sodium Salt

“…There is insufficient evidence regarding the effects of low-sodium salt on the occurrence of hyperkalemia, largely due to ethical issues related to enrolling participants with kidney disease in trials in which they would be exposed to potassium [17]. However, many studies excluded participants based on a self-reported history of chronic kidney disease [19,21,39] and therefore may have included individuals with advanced CKD who were unaware of their disease status. A large-scale trial on low-sodium salt that followed 21,000 high-risk adults in China over five years reported no increased risk of serious adverse events attributable to low-sodium salt use [21].…”

“…However, many studies excluded participants based on a self-reported history of chronic kidney disease [19,21,39] and therefore may have included individuals with advanced CKD who were unaware of their disease status. A large-scale trial on low-sodium salt that followed 21,000 high-risk adults in China over five years reported no increased risk of serious adverse events attributable to low-sodium salt use [21]. The trial excluded patients using potassium-sparing diuretics or potassium supplements and patients with serious kidney disease.…”

“…For the purpose of this paper, potassium-enriched low-sodium salt will be referred to as lowsodium salt, and sodium chloride (NaCl) will be referred to as regular salt. Randomized trials [16][17][18][19] have shown that low-sodium salt is effective in reducing both systolic and diastolic blood pressure, and modeling as well as a large-scale trial have documented reductions in cardiovascular disease and mortality [20,21]. This impact is likely not due to sodium reduction alone; a recent trial found a reduction in blood pressure despite urinary excretion data showing an increase in potassium intake but no change in sodium intake [19].…”

Understanding Barriers to Adherence to Optimal Treatment of Elevated Blood Pressure and Hypertension—Insights From Primary Care

“…1 Recent evidence has further confirmed the benefits of salt substitutes in terms of reduced rates of stroke, major cardiovascular events, and death. 2 The study by Liu et al 3 explores the acceptability of, and adherence to, a salt substitute as well as the barriers to sodium reduction. In this mixed-methods investigation conducted in rural China, participants from the Salt Substitute and Stroke Study were used.…”

A study protocol for the development of a SPIRIT extension for trials conducted using cohorts and routinely collected data (SPIRIT-ROUTINE)

“…Given the jurisdiction specific issues that may need to be addressed, I would have thought a broader search may beneficial. For example, Neal et al (2021) 1 is a great example of linkage to RCD in China.…”