SSaSS trial finds mortality benefit for salt substitute vs salt

Reducing the use of discretionary salt and using a salt substitute significantly reduced the risk of stroke and other cardiovascular events in a study of almost 21,000 older, high-risk participants in the Salt Substitute and Stroke Study (SSaSS), according to lead investigator Bruce Neal, MB, ChB, PhD, of the George Institute for Global Health, in Sydney, Australia.

The findings were reported as a late-breaking clinical trial in a Hot Line presentation at the European Society of Cardiology’s 2021 Congress, the Digital Experience and simultaneously published online by The New England Journal of Medicine.

“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 versus 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77-0.96; P=0.006), as were the rates of major cardiovascular events (49.09 events versus 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80-0.94; P<0.001) and death (39.28 events versus 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82-0.95; P<0.001),” they wrote.

The salt substitute used contained 25% potassium chloride, but Neal said the extra potassium did not increase the rate of hyperkalemia as the rate of hyperkalemia was essentially the same between the two study groups (3.35 events versus 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P=0.76).

The open-label, cluster-randomized trial was conducted among residents of 600 villages in rural China, Neal explained.

“This study is really, really important. It only costs pennies between salt and salt substitutes and to have this much impact, without any safety concerns is a really important public health finding,” said American College of Cardiology spokesperson Erin Donnelly Michos, MD, MHS.

In a phone interview with BreakingMED, Michos, who is director of women’s cardiovascular health and associate professor of medicine at Johns Hopkins University School of Medicine, added “these were really high-risk patients, but anyone can benefit from reducing salt. These are really definitive data. It’s a low-cost intervention and in underserved areas it can have such a meaningful impact.”

In an editorial published with the SSaSS findings, NEJM deputy editor Julie R. Ingelfinger, MD, wrote, “The results of the SSaSS appear impressive. If the strategy is feasible over time, the salt-substitute approach might have a major public health consequence in China, and possibly, elsewhere.”

But Ingelfinger had a few nits: “serial monitoring of potassium levels was not performed in the trial, and it is possible that hyperkalemic episodes were not detected. Furthermore, persons with a history of medical conditions that may be associated with hyperkalemia (e.g., chronic kidney disease) were not studied. Because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained. Finally, only one version of a salt substitute was used—75% sodium chloride and 25% potassium chloride; no salt substitutes with higher or lower potassium chloride concentrations were evaluated. Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability.”

During an ESC press briefing, BreakingMED asked Neal about the generalizability of the findings since discretionary salt use is much higher in China than in the United States, where sodium is more likely to come from processed foods, which are uncommon in China.

“I think that’s a very fair point. In developed countries, less salt is discretionary and it’s going to be less easy to replace,” Neal said. Nonetheless, he said that the evidence from SSaSS “is strong evidence to take to the food industry and say, you should be putting less added sodium into your products, and you should be careful not to leach out the potassium that is very often in the base product but doesn’t persist through to the final product.”

Michos agreed that the problem in the U.S. is the abundance of processed foods, which suggests that the time has come to pressure the food industry to change. “Remember the transfats ban? That same thing could occur with the food industry to make changes in processed food with more regulation of salt,” she said.

The participants in the intervention were given free salt substitutes, which they were asked to use as a replacement for regular salt and to use it in all cooking. But Neal also said that “they were asked to use the salt substitute more sparingly than they had previously used salt.”

In a prepared statement issued by the ESC, Neal said the “study provides clear evidence about an intervention that could be taken up very quickly at very low cost. A recent modelling study done for China projected that 365,000 strokes and 461,000 premature deaths could be avoided each year in China if salt substitute was proved to be effective. We have now showed that it is effective, and these are the benefits for China alone. Salt substitution could be used by billions more with even greater benefits.”

Neal said a kilo of the salt substitute used cost $1.62 compared to $1.08 for a kilo of salt.

“I think we can say the salt debate is over,” Michos said. “I do think that guidelines should change—including guidelines issued by the U.S. Department of Agriculture.”

  1. In the SSaSS trial, the use of salt substitutes was associated with a lower rate of stroke and cardiovascular events, as well as reduced mortality, compared to discretionary salt.
  2. Be aware that in the U.S. discretionary salt use is less than use in China, but processed foods are a significant source of sodium in U.S. diets.

Peggy Peck, Editor-in-Chief, BreakingMED™

The study was supported by the National Health and Medical Research Council (APP1164206 and APP1049417), with the study salt substitute purchased from local manufacturers in each province for years 1, 2, and 5 but provided free of charge by Jiangsu Sinokone Technology Company Limited for years 3 to 4.

Neal had no disclosures.

Ingelfinger is deputy editor of The New England Journal of Medicine.

Michos had no disclosures.


Cat ID: 204

Topic ID: 74,204,730,204,358,745,8,130,38,748,192,94,925,203