Salt substitutes decrease rates of stroke, cardiovascular events, and mortality: results from SSaSS

Key Points:

• The Salt Substitute and Stroke (SSaSS) study compared the effect of the consumption of a reduced sodium salt substitute to regular salt on stroke, cardiovascular events, and mortality.
• The trial, which was conducted in 600 villages in China, enrolled 35 participants from each village for a total of 20,995 participants.
• During almost 5 years of follow up, participants who consumed salt substitutes had significantly lower rates of all stroke, major adverse cardiac events, and total mortality. There was no evidence of harm with salt substitutes, and no significant increase in hyperkalemia.

Sodium has long been implicated as a major risk factor for hypertension, predisposing patients to adverse cardiac events, stroke, and premature death.  Salt substitutes were previously shown to lower blood pressure, and while this information was extrapolated to assume a reduction in adverse events, no study had directly established their effect on stroke, cardiovascular death, and mortality.

In a Hot Line session at the 2021 European Society of Cardiology Congress today, Dr. Bruce Neal (George Institute for Global Health) presented the results of the impressive SSaS study, an open-label, cluster-randomized trial that enrolled participants from 600 villages in rural China. Participants in the intervention villages were given salt substitutes, a combination of 75% sodium chloride and 25% potassium chloride, for free as an alternative to regular salt. Participants were instructed to use this substitute in cooking, preservation, and seasoning, and were told to use it more judiciously than they normally would. Each participant was given enough substitute to provide for their respective families as well. The control participants were allowed to continue with their normal sodium consumption habits.

A total of 20,995 participants were enrolled. Over a median follow up period of 4.74 years, salt substitute was associated with a significant decrease in stroke (29.14 versus 33.65 per 1,000 patient years, rate ratio [RR] 0.86; 95% confidence interval [CI] 0.77–0.96; p=0.006). For the secondary outcome of major cardiovascular events, salt substitute was also associated with fewer events (49.09 versus 56.29 per 1,000 patient-years; RR 0.87; 95% CI 0.80–0.94; p<0.001). Finally, mortality followed the trend as well, (39.27 in the substitute group versus 44.61 per1,000 patient-years; RR 0.88; 95% CI 0.82–0.95; p<0.001). There was no difference in serious adverse events and/or hyperkalemia in either group.

After the results, Dr. Neal was congratulated for this large-scale, pragmatic trial, applicable to such large portions of the world, especially where table salt is the primary mode of sodium consumption. In response to the trial, he told Cardiology Now News “It was a pretty massive undertaking. We chose China because there were logistical aspects that made it favorable to us. They key question is ‘what is the generalizability of this study?’ and my view is that it is very generalizable as humans’ ability to process sodium is pretty constant across communities and countries. The benefit will likely be seen in lower income countries, but everybody could derive some benefit”.

The trial results were simultaneously published in the New England Journal of Medicine.