Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke and death from all causes and cardiovascular disease (CVD), a meta-analysis has revealed.
The blood pressure-mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28bn people worldwide with high blood pressure, the researchers say.
“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure and prevent major cardiovascular events,” they write in their study, which was published online in Heart.
Strong support for landmark study
In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride, known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, write Maoyi Tian, PhD, with Harbin Medical University, Harbin, China, and the George Institute for Global Health, Sydney, Australia, and colleagues in their article.
In the landmark Salt Substitute and Stroke Study (SSaSS) – reported in MedicalBrief on 15 September 2021 – salt substitutes cut the risk of MI, stroke and early death. But the study was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world, reports Medscape.
To investigate, Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomised controlled trials published through August 2021 with 31 949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South-East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.
A meta-analysis of blood pressure data from 19 trials that included 29 528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% CI, -6.07 to -3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, -2.42 to -0.79).
The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.
Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, -3.02 to -0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, -1.78 to -0.12; P = .025) greater reduction in DBP.
Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.
Clear benefit on hard outcomes
Pooled data on clinical outcomes from five trials that included 24 306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio [RR], 0.89; 95% CI, 0.85 – 0.94), CV mortality (RR, 0.87; 95% CI, 0.81 – 0.94), and CV events (RR, 0.89; 95% CI, 0.85 – 0.94).
Tian and colleagues said: “Broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”
They added, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium”.
Offering perspective on the study, Dr Harlan Krumholz of Yale New Haven Hospital and Yale School of Medicine, Connecticut, said it provided “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context”.
At this point, he thinks salt substitutes “could be included in recommendations to patients”.
“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” he said.
Dr Johanna Contreras, heart failure and transplant cardiologist at the Mount Sinai Hospital in New York, agreed that in the absence of contraindications, salt substitutes should be recommended.
“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” she said.
“People who don’t have high blood pressure should limit salt intake because if you have high blood pressure in your family – even if you don't have high blood pressure in your 20s or 30s – you’re likely to develop it.”
Study details
Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis
Xuejun Yin, Anthony Rodgers, Adam Perkovic, Liping Huang, Ka-Chun Li,
Jie Yu, Yangfeng Wu, J H Y Wu, Matti Marklund, Mark Huffman, Jaime Miranda, Gian Luca Di Tanna, Darwin Labarthe, Paul Elliott, Maoyi Tian, Bruce Neal
Published in Heart on 10 August 2022
Abstract
Objectives The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.
Methods
We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.
Results
There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was −4.61 mm Hg (95% CI −6.07 to −3.14) and of diastolic blood pressure (DBP) was −1.61 mm Hg (95% CI −2.42 to −0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a −1.53 mm Hg (95% CI −3.02 to −0.03, p=0.045) greater reduction in SBP and a −0.95 mm Hg (95% CI −1.78 to −0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).
Conclusions
The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.
Medscape article – More Evidence Salt Substitutes Lower Risk of CVD and Death (Open access)
See more from MedicalBrief archives:
Salt substitute reduces stroke, CV events and mortality risk — SSaSS trial
Healthy diet not offsetting negative effects of high salt intake
Contentious study shows reduced salt consumption not necessary for cardiac health
Sodium restriction in heart failure should be taken with a pinch of salt