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<reference>
Salt Substitute Reduces Stroke, CV Events, and Death

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, the new landmark SSaSS shows.

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News
>
Medscape Medical News
>
Conference News
>
ESC 2021

Salt Substitute Shows Clear Reduction in Stroke, CV Events, and Death

Sue Hughes

August 29, 2021

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in
stroke
, cardiovascular events, and death, a new landmark study shows.

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on August 29 at the virtual
European Society of Cardiology (ESC) Congress 2021
. They were simultaneously
published online
in the
New England Journal of Medicine (NEJM)
.

"This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention," Neal concluded. "This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical," he added.

Addressing the issue of whether these results are generalizable to other populations, Neal said, "We believe the results are relevant to everyone who eats salt."

"The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations," he said. "Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this."

Commentators at the ESC presentation lauded the study as "magnificent," with "extraordinary" results and "very powerful implications."

Designated discussant, hypertension expert Bryan Williams, MD, University College London, United Kingdom, said the SSaSS was "probably the most important study with regards to public health that we will see." He described the reductions in stroke, cardiovascular events, and death as "extraordinary for such a simple intervention."

Williams added: "Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin."

He also highlighted the large number of events in the trial. "This was a large, pragmatic, long-duration study in a high-risk population, and with 5000 cardiovascular events it gives enormous power to show benefits."

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford, United Kingdom, said the SSaSS "will change the way we think about salt and be remembered for years to come."

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan School of Medicine, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

"For patients with diabetes, this is a really important intervention," he stated.

However, an
editorial
accompanying the
NEJM
publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with
hyperkalemia
were not studied.

She also notes that 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.

"Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability," she concludes.

Cluster-Randomized Trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had
uncontrolled hypertension
. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (approximately 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1000 person-years in the salt substitute group vs 33.65 events per 1000 person-years with regular salt (rate ratio, 0.86; 95% CI, 0.77 - 0.96;
P
= .006).

The rates of major cardiovascular events were 49.09 events per 1000 person-years in the salt substitute group vs 56.29 events per 1000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80 - 0.94;
P
< .001).

And the rate of death was 39.28 events per 1000 person-years with the salt substitute vs 44.61 events per 1000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82 - 0.95;
P
< .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 - 1.37;
P
= .76).

Neal reported that 7% to 8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.

Food Manufacturers Must Make Changes

Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt — salt added at home at the time of cooking for preservation of food or seasoning. "This is salt that is easy to replace with salt substitute," Neal noted.

"There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt — mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute."

He pointed out that salt substitute is low cost and is easy to manufacture. "Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch."

Neal believes the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

"This study provides strong evidence to take to the food industry," he concluded. "We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes."

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Neal reports no disclosures. Ingelfinger is employed by the
New England Journal of Medicine
as deputy editor.

European Society of Cardiology (ESC) Congress 2021. Presented August 29, 2021.

N Engl J Med
. Published online August 29, 2021.
Abstract
,
Editorial

For more from theheart.org | Medscape Cardiology, join us on
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Medscape Medical News © 2021 WebMD, LLC

Send comments and news tips to
news@medscape.net
.

Cite this: Salt Substitute Shows Clear Reduction in Stroke, CV Events, and Death -
Medscape
- Aug 29, 2021.

Authors and Disclosures

Authors and Disclosures

Journalist

Sue Hughes

Freelance News Editor, Medscape

Disclosure: Sue Hughes has disclosed no relevant financial relationships.

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</reference>

<statements>
1. Sodium–potassium substitution reduced stroke, major cardiovascular events, and death in a high-risk trial (rate ratios 0.86, 0.87, and 0.88)
2. SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older with uncontrolled hypertension; patients with severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded
3. The intervention group used a salt substitute of approximately 75% sodium chloride and 25% potassium chloride, while the control group continued regular salt
4. In the Medscape report of the trial results, mean follow-up was 4.74 years and systolic blood pressure was reduced by 3.3 mmHg in the substitute group
5. The outcome and safety statistics are summarized below
6. In the Salt Substitute and Stroke Study results table, stroke was an outcome.
7. In the Salt Substitute and Stroke Study results table, the stroke rate in the salt-substitute group was 29.14 events per 1000 person-years.
8. In the Salt Substitute and Stroke Study results table, the stroke rate in the regular-salt group was 33.65 events per 1000 person-years.
9. In the Salt Substitute and Stroke Study results table, the rate ratio for stroke was 0.86 (95% CI 0.77–0.96; P = .006).
10. In the Salt Substitute and Stroke Study results table, major cardiovascular events were an outcome.
11. In the Salt Substitute and Stroke Study results table, the major cardiovascular events rate in the salt-substitute group was 49.09 events per 1000 person-years.
12. In the Salt Substitute and Stroke Study results table, the major cardiovascular events rate in the regular-salt group was 56.29 events per 1000 person-years.
13. In the Salt Substitute and Stroke Study results table, the rate ratio for major cardiovascular events was 0.87 (95% CI 0.80–0.94; P < .001).
14. In the Salt Substitute and Stroke Study results table, death was an outcome.
15. In the Salt Substitute and Stroke Study results table, the death rate in the salt-substitute group was 39.28 events per 1000 person-years.
16. In the Salt Substitute and Stroke Study results table, the death rate in the regular-salt group was 44.61 events per 1000 person-years.
17. In the Salt Substitute and Stroke Study results table, the rate ratio for death was 0.88 (95% CI 0.82–0.95; P < .001).
18. In the Salt Substitute and Stroke Study results table, serious adverse events attributed to hyperkalemia were an outcome.
19. In the Salt Substitute and Stroke Study results table, the serious adverse events attributed to hyperkalemia rate in the salt-substitute group was 3.35 events per 1000 person-years.
20. In the Salt Substitute and Stroke Study results table, the serious adverse events attributed to hyperkalemia rate in the regular-salt group was 3.30 events per 1000 person-years.
21. In the Salt Substitute and Stroke Study results table, the rate ratio for serious adverse events attributed to hyperkalemia was 1.04 (95% CI 0.80–1.37; P = .76).
22. In the Medscape report, Neal said the way the body manages sodium and potassium and their association with blood pressure is highly consistent across populations, and he stated that almost everyone, except people with serious kidney disease, should expect some benefit from switching to a salt substitute
23. The same report conveyed Neal’s interpretation that 7% to 8% of the control group began using the substitute during the study, which may have underestimated the true effect, and that the product was low-cost and easy to manufacture, costing around 50% more than regular salt or roughly a dollar or two per person per year
24. These are investigators’ interpretations as reported in a secondary news article, not independent trial measurements
25. The same Medscape report noted that an accompanying editorial gave a less enthusiastic response: Julie R. Ingelfinger pointed out that serial monitoring of potassium levels was not performed, so hyperkalemic episodes may not have been detected, and persons with conditions associated with hyperkalemia were not studied
26. The editorial also noted that household members without risk factors were not analyzed and that wider effectiveness is hard to predict given limited generalizability
27. Taken together, the reported trial results indicate that sodium–potassium substitution can reduce hard cardiovascular outcomes in a high-risk rural Chinese population, but the evidence does not establish that the same substitution is safe or equally effective in all populations, especially those at risk for hyperkalemia
28. Salt substitution reduces stroke, major cardiovascular events, and death, but the trial’s population, exclusion of kidney disease and potassium-related risk, and lack of serial potassium monitoring limit broad generalization
29. Salt substitution shows that hard outcomes can improve through a simple dietary intervention, but safety and generalizability remain constrained by kidney disease and hyperkalemia risk
</statements>

Begin the assessment now. Output only the JSON list, without any conversational text or explanations.