Salt substitute may slash stroke risk

Swapping regular salt for a reduced-sodium salt substitute may cut stroke, major adverse cardiovascular event (MACE)*, and death rates in individuals with a risk of stroke, according to results of the SSaSS** trial.

“SSaSS is the first large trial of a salt-reduction strategy to show inequivalent evidence of benefit for clinical outcomes,” remarked principal investigator Professor Bruce Neal from The George Institute for Global Health, Sydney, Australia, at ESC 2021.

“Using a salt substitute instead of regular salt reduced the risk of stroke, MACE, and death, with no evidence of any risk from added dietary potassium,” he said.

The open-label, cluster-randomized trial was conducted in rural areas in five provinces in China and included adults with a history of stroke or aged ≥60 years with poorly controlled blood pressure (systolic blood pressure [SBP] ≥140 or ≥160 mm Hg for those receiving or not receiving treatment, respectively). About 35 individuals were recruited from each of the 600 participating villages, yielding a cohort of 20,995 participants (mean age 65.4 years, 49.5 percent female). They were randomized 1:1 (by village) to receive a salt substitute provision (~75 percent sodium chloride, 25 percent potassium chloride by mass) amounting to approximately 20 g/person/day (intervention group) or continue consumption of regular salt (100 percent sodium chloride; control group).

About 73 percent of participants had a history of stroke and 88.4 percent had a history of hypertension. Mean BP was 154.0/89.2 mm Hg and 79.3 percent were on ≥1 BP-lowering medications. They were followed up for a mean 4.74 years. Participants in the intervention group were requested to replace regular salt with the salt substitute for all salt-use purposes and to reduce their use of the substitute compared to previous salt use. Those in the control group continued their regular salt usage. There were about 3,000 strokes, 4,000 deaths, and 5,000 MACE during the follow-up period.

Use of the salt substitute was associated with a 14 percent reduced rate of fatal or nonfatal stroke compared with regular salt use (29.14 vs 33.65 events per 1,000 person-years [PYs]; rate ratio [RR], 0.86, 95 percent confidence interval [CI], 0.77–0.96; p=0.006). [ESC 2021, Hot Line session, N Engl J Med 2021;doi:10.1056/NEJMoa2105675]

MACE incidence was reduced by 13 percent with the salt substitute compared with regular salt (49.09 vs 56.29 events per 1,000 PYs; RR, 0.87, 95 percent CI, 0.80–0.94; p<0.001), while death rate was reduced by 12 percent (39.28 vs 44.61 events per 1,000 PYs; RR, 0.88, 95 percent CI, 0.82–0.95; p<0.001).

Rates of death due to vascular causes were also reduced with the salt substitute vs regular salt (22.9 vs 26.3 events per 1,000 PYs; RR, 0.87), as were nonfatal ACS rates (3.8 vs 5.1 events per 1,000 PYs; RR, 0.70). However, there was no between-group difference pertaining to nonfatal stroke (22.4 vs 24.9 events per 1,000 PYs; RR, 0.90).

The benefits of the salt substitute were apparent across subgroups and prespecified exploratory outcomes of stroke and death, noted the authors.

 

No increased hyperkalaemia risk

In terms of safety, the rates of serious adverse events (AEs) due to definite, probable, or possible hyperkalaemia did not significantly differ between the salt substitute and regular salt groups (3.35 vs 3.30 events per 1,000 PYs; RR, 1.04, 95 percent CI, 0.80–1.37; p=0.76). No other serious AEs were documented with the use of the salt substitute.

“The absence of any evident increased risk of clinical hyperkalaemia addresses concerns about the potential harms from the use of salt substitutes,” the authors said.

The lack of serial potassium assessments may have affected accurate estimation of hyperkalaemia incidence, noted Neal. However, routine searching of databases for hyperkalaemia incidence for all participants revealed no excess risk. There was also no increased risk of sudden cardiac death which could be caused by hyperkalaemia-induced arrhythmias, he said.

 

A low-cost solution for a major problem

“This study provides clear evidence about an intervention that could be taken up very quickly at very low cost,” Neal pointed out.

“The trial result is particularly exciting because salt substitution is one of the few practical ways of achieving changes in the salt people eat. Other salt reduction interventions have struggled to achieve large and sustained impact,” he continued.

“Both higher dietary sodium consumption and lower potassium consumption are associated with elevated BP levels. Potassium-enriched salt substitutes combine the benefits of sodium reduction and potassium supplementation for BP lowering,” he said, noting that the mean difference in SBP between the two groups in this study was -3.34 mm Hg.

According to Neal, these results are probably generalizable to other populations. “The physiology of sodium, potassium, and BP is incredibly constant across diverse populations. If you get a BP reduction with salt substitution, you’re very likely to get clinical benefits as well,” he commented.

“Almost everyone, except a few people with serious kidney disease who should be avoiding salt anyway, could switch to using a salt substitute and expect to see some sort of benefit.” Individuals who consume large amounts of discretionary salt are likely to incur the greatest benefit from this substitution, he concluded.