Replacing salt with a low-sodium option lowers the risk of stroke in persons with high blood pressure or past stroke.
According to late-breaking data presented in a Hot Line session at ESC Congress 2021 and published in the New England Journal of Medicine, replacing salt with a low-sodium option lowers the risk of stroke in persons with high blood pressure or past stroke. 
High blood pressure and an increased risk of cardiovascular disease and early death are linked to both high salt and inadequate potassium intake.[3,4] Salt substitutes, which replace a portion of the sodium chloride in ordinary salt with potassium chloride, have been proven to lower blood pressure, but their consequences on heart disease, stroke, and death were unknown. Furthermore, there were worries that hyperkalemia could cause cardiac arrhythmias and abrupt death in persons with chronic kidney disease.
The Salt Substitute and Stroke Study (SSaSS) looked at the effects of a low-sodium salt substitute versus conventional salt on stroke, cardiovascular events, mortality, and clinical hyperkalemia. Between April 2014 and January 2015, participants in the SSaSS experiment were enrolled in an open, cluster-randomized trial. Adults having a history of stroke or who were 60 years or older and had poorly regulated blood pressure were included in the study. 
The trial was carried out in 600 villages across five Chinese regions. Within each province, two counties were chosen to represent the socioeconomic development level of the province’s rural counties. A total of 20,995 people were recruited from each village, for a total of 35 people in each village. Participants were randomized in a 1:1 ratio by village to receive a salt substitute or continue to consume conventional salt.
Participants in intervention villages were provided a free salt substitute (about 75 percent sodium chloride and 25 percent potassium chloride) to use as a substitute for ordinary salt in all cooking, seasoning, and food preservation. To maximize their sodium decrease, individuals were also advised to use the salt substitute more sparingly than they had previously used salt. There was enough salt replacement to meet the demands of the entire household (about 20 g per person per day). Participants in the control villages went about their daily routines as usual.
Participants were 65.4 years old on average, with 49.5 percent of them being female. 72.6 percent had previously had a stroke, and 88.4 percent had previously experienced hypertension.
Over 3,000 persons had a stroke, over 4,000 died, and over 5,000 experienced a significant cardiovascular event over an average follow-up of 4.74 years. When compared to ordinary salt, the risk of stroke was lower with salt substitute (29.14 versus 33.65 per 1,000 patient-years; rate ratio [RR] 0.86; 95 percent confidence interval [CI] 0.77–0.96; p=0.006).
In terms of secondary outcomes, total mortality (39.27 versus 44.61 per 1,000 patient-years; RR 0.88; 95 percent CI 0.82–0.95; p0.001) and major cardiovascular events (non-fatal stroke, non-fatal acute coronary syndrome, vascular death) were both reduced with salt substitute (49.09 versus 56.29 per 1,000 patient-years; RR 0.87; 95 percent CI 0.80–0.94; p0.001).
In terms of safety, there was no difference between salt substitute and conventional salt in terms of major adverse events due to clinical hyperkalemia (3.35 versus 3.30 per 1,000 patient years; RR 1.04; 95 percent CI 0.80–1.37; p=0.76). There were no further dangers discovered.
“This study gives unambiguous evidence for an intervention that might be taken up very rapidly at very low cost,” said principal investigator Professor Bruce Neal of the George Institute for Global Health in Sydney, Australia. A recent modeling research for China estimated that if salt substitutes were proven to be effective, 365,000 strokes and 461,000 premature deaths may be averted per year.  We’ve now demonstrated that it works, and these are the benefits to China alone. Hundreds of millions more people could benefit from salt substitution.”
‘’Most importantly, salt replacement is both simple to make and inexpensive. In China, a kilo of ordinary salt costs roughly US$1.08 and lasts for months. He stated that a kilo of salt replacement costs $1.62/kg. “When it comes to food preparation and cooking, it is generally lower-income and more disadvantaged populations who use a lot of salt.  This suggests that salt substitutes have the potential to alleviate cardiovascular disease-related health disparities.”
References and notes
- SSaSS: Salt Substitute and Stroke Study into the effect of salt substitutes on cardiovascular events and death
- Tian M, et al. The effect of salt substitute on cardiovascular events and death (SSaSS). N Engl J Med. 10.1056/NEJMoa2105675
- Cogswell ME, Mugavero K, Bowman BA, Frieden TR. Dietary sodium and cardiovascular disease risk–measurement matters. N Engl J Med. 2016;375:580–586.
- Aburto NJ, Hanson S, Gutierrez H, et al. Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ. 2013;346:f1378.
- Greer RC, Marklund M, Anderson CAM, et al. Potassium-enriched salt substitutes as a means to lower blood pressure. Hypertension. 2020;75:266–274.
- Neal B, Tian M, Li N, et al. Rationale, design, and baseline characteristics of the Salt Substitute and Stroke Study (SSaSS)-A large-scale cluster randomized controlled trial. Am Heart J. 2017;188:109–117.
- Poorly controlled blood pressure was defined as: systolic blood pressure =140 mmHg if on blood pressure lowering medication or systolic blood pressure =160 mmHg if not on blood pressure lowering medication.
- Marklund M, Singh G, Greer R, et al. Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study. BMJ. 2020;369:m824.
- Bhat S, Marklund M, Henry ME, et al. A systematic review of the sources of dietary salt around the world. Adv Nutr. 2020;11:677–686.
Funding: 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.