Salt Substitute May Reduce Stroke Risk, Death in Older Individuals


Findings of the Salt Substitute and Stroke Study suggest a switch to salt substitute could reduce the risk of stroke by 13% in those with a history of hypertension or stroke.

Bruce Neal, MBChB, PhD, executive director, George Institute for Global Health

Bruce Neal, MBChB, PhD

A version of this article originally appeared on our sister site, Practical Cardiology.

Data from the Salt Substitute and Stroke Study (SSaSS), presented at the European Society of Cardiology Congress 2021, suggest that salt substitutes with reduced sodium levels and increased potassium levels could significantly reduce the risk of stroke and death in older individuals with hypertension or a history of stroke.1

The results of the open-label study conducted in 600 villages across rural China showed that the use of a salt substitute was associated with a lower rate of stroke, major adverse cardiovascular events, and death over a follow-up period of 5 years, which investigators noted could have implications for the larger, global population.

“This study provides clear evidence about an intervention that could be taken up very quickly at very low cost,” principal investigator Bruce Neal, MBChB, PhD, executive director, George Institute for Global Health, said in a statement.2 “A recent modeling study done for China projected that 365,000 strokes and 461,000 premature deaths could be avoided each year in China if a salt substitute was proved to be effective. We have now shown that it is effective, and these are the benefits for China alone. Salt substitution could be used by billions more with even greater benefits.”

The data included a total of 20,995 patients who were enrolled in the trial, who were randomly assigned to the salt-substitute group (n = 10,504) or the regular salt group (n = 10,491). Those randomized to the salt substitute reported stroke rates of 29.14 events per 1000 person-years compared with 33.65 events per 1000 person-years in the regular salt group (RR, 0.86 [95% CI,0.77-0.96]; P = .006). Lower rates of major adverse cardiovascular events were also associated with the salt substitute group, with an event rate of 49.09 events per 1000 person-years in the substitute group compared with 56.29 per 1000 person-years in the regular salt group (RR, 0.87 [95% CI, 0.87-0.94]; P <.001).

READ MORE: FDA Approves Vivistim VNS System for Ischemic Stroke Motor Deficits

Investigators also pointed out a lower rate of death was observed in the salt substitute group, with an event rate of 39.28 per 1000 person-years compared to 44.61 per 1000 person-years in the regular salt group (RR, 0.88 [95% CI, 0.82-0.95]; P <.001). Results of a safety analysis suggested the rate of serious adverse events attributable to hyperkalemia was not significantly higher among those receiving salt substitute than those receiving regular salt, with an event rate of 3.35 per 1000 person-years with the salt substitute and 3.30 per 1000 person-years with regular salt (RR, 1.04 [95% CI, 0.80-1.37]; P=.76).

“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,” Neal added.2 Despite the known associations between increased levels of dietary sodium consumption and cardiovascular risk, little literature exists to offer evidence of an effective method to reduce sodium intake, as well as the determination of the effectiveness of such methods to subsequently reduce cardiovascular risk.

In this study, Neal and colleagues conducted an open-label, cluster-randomized trial conducted in villages in rural areas of 5 provinces in China, enrolling more than 20,000 patients from April 2014 to January 2015 and aimed to follow each participant for 5 years. The study cohort had a mean age of 65.4 years, 49.5% were female, 72.6% had a history of stroke, and 88.4% had a history of hypertension. The mean duration of follow-up was 4.74 years.

Patients included in the trial had to have a history of stroke or be at least 60 years of age or older and have hypertension. Villages included in the study were randomized in a 1:1 ratio to the intervention group or a control group. Patients randomized to the intervention group received a substitute that was 75% sodium chloride and 25% potassium chloride by mass and those in the control group continued to use regular salt.

As the authors suggest, these findings present potential larger implications for the reduction of stroke among those with a history of the condition. This comes just a few months after the American Heart Association/American Stroke Association (AHA/ASA) published updated 2021 guidelines for the prevention of secondary stroke in patients with stroke and transient ischemic attack (TIA) in May.3

These new guidelines focus on improving diagnostics, managing vascular risk factors and lifestyle factors, altering patient behaviors, recommending antithrombotic therapy, monitoring atrial fibrillation (AF), extracranial carotid artery disease, severe intracranial stenosis, and embolic stroke of uncertain source, and the determinant use of patent foramen ovale closure.

For more on the results of SSaSS and their implications on real-world risk reduction, check out this video interview that Practical Cardiology conducted with Neal about the findings. For more from the ESC Congress 2021, head to

1. Neal B, Wu Y, Feng X, et al. Effect of Salt Substitution on Cardiovascular Events and Death. N Engl J Med. Published online August 29, 2021. doi: 10.1056/NEJMoa2105675
2. Low-sodium salt prevents stroke. News release. ESC Congress. August 29, 2021. Accessed August 30, 2021.
3. Kleindorfer DA, Towfighi A, Chaturvedi S, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American Heart Association/American Stroke Association. Stroke. Published online May 24, 2021 doi: 0.1161/STR.0000000000000375
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