Salt Substitute Reduces Risks of Cardiovascular Events

Bruce Neal, MB, ChB, PhD

A recent open-label, cluster-randomized trial from China found that salt substitute resulted in lower rates of stroke, major cardiovascular events, and death in people with a history of stroke or older people (60 years or more) with high blood pressure as opposed to regular salt.

The findings were presented at the European Society of Cardiology (ESC) 2021 Congress this weekend.

The associations between elevated sodium consumption, high blood pressure, and increased risk of cardiovascular disease and death were well established prior to the research. Additionally, salt substitutes were known to lower blood pressure due to their reduced sodium levels and increased potassium levels.

However, the effects of salt substitutes on cardiovascular and safety outcomes in people were uncertain.

As such, the investigators led by Bruce Neal, MB, ChB, PhD, the George Institute for Global Health, Australia, conducted the The Salt Substitute and Stroke Study (SSaSS).

The study was designed to define the overall balance of benefits and risks of salt substitute as compared with regular salt on stroke, cardiovascular events, death, and clinical hyperkalemia.

The Study

A total of 20,995 people were enrolled in the study from April 2014 to January 2015.

Participants were taken from 600 villages in rural areas of 5 Chinese provinces, which were Hebei, Liaoning, Ningxia, Shanxi, and Shaanxi.

Participants were adults with a history of stroke or who were aged 60 years or older with poorly controlled blood pressure.

Villages selected were then randomly assigned to the intervention group (salt substitute) or to the control group.

Follow-ups were done at 6-month intervals and focused on trial outcomes, hospitalizations, and other serious illnesses.

Due to the COVID-19 pandemic, the completion of the trial was moved to the first quarter of 2021, and 5-year follow-up visits were also conducted later than scheduled.

All 5-year follow-ups were conducted in person, and potential events prior to the meetings were identified through databases of health insurance records from the New Rural Cooperative Medical Scheme and National Mortality Surveillance System.

The investigators established the primary outcome as stroke, and the secondary outcomes as major adverse cardiovascular events and death.

The Results

During the study, 4172 participants had died. The remaining 15,130 people were seen up to the final follow-up visit.

Across the follow-up period, the mean difference in 24-hour urinary sodium excretion between the salt-substitute group and the regular-salt group was −350 mg (95% confidence interval [CI], −545 to −154) (−15.2 mmol; 95% CI, −23.7 to −6.7), and the mean difference in 24-hour urinary potassium excretion was 803 mg (95% CI, 714 to 897).

Additionally, the rate of fatal or nonfatal stroke events was significantly lower in the salt-substitute group than in the regular-salt group (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% CI, 0.77 to 0.96)

Compared to salt, the salt substitute was shown to protect against secondary outcomes of major cardiovascular events and death from any cause, and it was not associated with any apparent adverse events.

Overall, the findings in the present study were consistent with what was observed in smaller studies. Despite some limitations, such as the lack of serial measurements of potassium, Neal and colleagues were confident that the findings presented in their study could result in prominent health benefits in the future.

"We note that the magnitude of protection observed in this trial is similar to that assumed in a recent modeling study that estimated that 365,000 strokes, 461,000 premature deaths, and 1,204,000 vascular events could be averted each year by the population-wide use of a salt substitute in China,” the team wrote.

“Large benefits might also be achieved in other countries in Asia, Africa, and Latin America in which salt intake is above recommended levels.”