Salt Substitutes Could Have BP, CV Benefits Worldwide: Meta-analysis

Salt substitutes can help improve blood pressure and lower the risks of stroke, major cardiovascular events, and all-cause mortality across a wide variety of patient subgroups and geographies, according to a new meta-analysis.

The new data build off of what was demonstrated in the large Salt Substitute and Stroke Study (SSaSS), conducted across 600 villages in rural China, and also generalize the findings to a wider demographic, the authors say. That’s key, since one of the key questions in the wake of SSaSS was whether the findings would bear fruit outside of this nonurban Chinese population.

“All results confirmed our initial hypothesis,” study co-author Maoyi Tian, PhD, MSc (Harbin Medical University, China), told TCTMD in an email. “That includes consistent beneficial effects on blood pressure; the blood pressure-mediated effects for stroke, major cardiovascular events and premature mortality [being] likely generalizable to diverse population subgroups; and no evidence that higher dietary potassium was associated with any health harms.”

For the study, published online recently in Heart, Xuejun Yin, MPH (University of New South Wales, Newtown, Australia), Tian, and colleagues included data on 31,949 participants from 21 randomized trials—including 20,995 from SSaSS—looking at salt substitutes across the globe.

Among the 19 studies that looked at the effects of salt substitutes on blood pressure, there were overall -4.61 mm Hg and -1.61 mm Hg drops in systolic and diastolic blood pressures, respectively for those who used salt substitutes compared with controls (P < 0.001 for both).

Larger blood pressure reductions were observed in trials that ran less than 12 months, in patients who had higher levels of potassium intake at baseline, and in those who took a salt substitute with a lower proportion of NaCl. Otherwise, the effects of salt substitute use on blood pressure were consistent and favorable across countries from World Health Organization regions, and among population strata defined by age, sex, history of hypertension, body mass index, baseline blood pressure, and baseline 24-hour urinary sodium excretion.

The vast majority of outcomes data came from SSaSS findings and showed lower risks of all-cause mortality (RR 0.89; 95% CI 0.85-0.94), cardiovascular mortality (RR 0.87; 95% CI 0.81-0.94), and MACE (RR 0.89; 95% CI 0.85-0.94) with salt substitute groups compared with controls.

Additionally, data from 13 trials showed a reduction in urinary sodium excretion of 0.48 g/day and an increase in urinary potassium excretion of 0.45 g/day with salt substitute use (P < 0.001 for both).

“Potassium-enriched salt, such as that used in the SSaSS, should be considered routinely by clinicians seeking to prevent complications in patients with hypertension and by policy makers seeking to reduce the burden of blood pressure-related disease,” the authors write.

‘Stronger Joint Effect’

Commenting on the study for TCTMD, Nancy Cook, ScD (Brigham and Women’s Hospital, Boston, MA), said this is the first meta-analysis to include SSaSS data. “It's well known that increasing potassium and decreasing sodium improve blood pressure,” she observed. “A salt substitute really tends to magnify the effect, [as] they tend to have a stronger joint effect.”

Even though some of the other studies included here were “miniscule,” with as few as 20 participants, they all had findings “pointing in the same direction,” Cook added. “It's very helpful to see that.”

She warned that it’s possible that “some of the salt substitutes in other studies included other minerals like magnesium or maybe calcium” that could potentially have their own beneficial effects. But these “don't seem to be as strong as potassium in general,” Cook added.

Ultimately, salt substitutes “seem like a good idea” for most people with hypertension seeking to reduce their risk of adverse events, she said. “Certainly, there are some people who cannot tolerate that, like someone with underlying kidney disease, and there's always that concern. You can't just use it in basic ingredients in food products, for example, without some warning. But in general, those with blood pressure issues would probably benefit from them.”

In the future, Cook said she would like to see more research tease out the mechanisms behind how potassium substitution affects blood pressure, and perhaps even look at potassium supplementation instead of substitution. “The other thing is there's some question whether the effect is only through blood pressure,” she added. “There might be other effects on the vasculature that might be in addition to excess blood pressure itself, but those aren't really known well enough.”

Tian said he would like to see future research addressing implementation so as to understand better how “to scale up the use of salt substitutes in diverse population subgroups and geographies.”