COMMENTARY

Salt and CVD Controversies: What’s Shaking?

Bruce Neal MB ChB, PhD; Michel Burnier, MD

Disclosures

September 02, 2019

This transcript has been edited for clarity, but is not yet copyedited.

Bruce Neal MB ChB, PhD: Hello I’m Bruce Neal from the The George’s Institute for Global Health at the University of New South Wales, Australia, I'm joined here today by Michel Burnier from the University Lausanne in Switzerland. We're going to talk through some current controversies around the issue of salt and cardiovascular health. I'm going to turn over, first of all to Michel and ask him to summarize recent research that was just presented here at the European Society of Cardiology Congress.

Salt Substitution Study

Michel Burnier, MD: I would like to summarize a very interesting Peruvian study, which was done in six rural villages, where they went into the homes took out the regular salt, sodium chloride, and replaced it with a salt substitute that was rich in potassium. The goal was to reduce the sodium intake and also to increase the potassium intake. They not only measured blood pressure as previous studies have done, but they also looked at the incidence of new cases of hypertension in these populations where most people were not hypertensive at baseline.

And, as expected, they found a significant decrease in blood pressure, both in normotensive and hypertensive participants. As also expected the decrease was greater in the hypertensives. This was seen in a similar study done in Portugal years ago.

What was interesting to me is that when they looked at the incidence of new cases of hypertension, they demonstrated a 50% reduction. To me, this is a good indication that at the population level, if one reduces the salt intake, and also increases the potassium intake, which may be an important factor in this study, we can actually prevent the development of hypertension. We don't yet know if we’re just delaying it a couple of years or more, but at the population level it had a significant effect.

Neal: I have a couple of questions. One of the things that struck me was that the reduction in systolic blood pressure was pretty small, about 1-2 mm Hg, but the reduction in incident hypertension was 50%. The two of those seem incongruous to me.

Burnier:   In the general population, it was about 1.2 mm Hg and in the hypertensives it was closer to 2 mm Hg but, if you look at the epidemiological studies a drop of 2 mm Hg corresponds to an important treatment effect at the population level. That also probably means that a lot of these patients or rather subjects, were on the cusp of hypertension. I think the normotensives were probably not really low, but intermediate, say around 140/90 mm Hg.

Maybe there’s a discrepancy between the smaller reduction in SBP and the huge 50% decrease in the risk of hypertension, but it confirms what we used to say that every mm Hg counts.

Neal: One of the other things we have to consider with this trial is that it was a substantial project over a reasonable timeframe, but it had only a limited number of clusters. There were a limited number of people, and there's probably a degree of imprecision in some of the estimates.

They might have underestimated the blood pressure a bit and they might have overestimated the effect on hypertension as well.

Burnier: That's true and we cannot exclude the possibility of some salt contamination.

Neal: That's another interesting point because they got an increase in potassium, but they didn't get a reduction in sodium levels.

Burnier:  Yes, that was quite surprising. We have seen in other studies that when you reduce sodium and add potassium, people tend to use more [of the salt substitute]. Are the findings due to the decrease in sodium because overall in terms of 24 hour urine they didn’t see a decrease? Or is it due to the potassium?

There are lots of studies showing that potassium has a beneficial effect, not only in terms of blood pressure reduction. If you increase intake, you also promote sodium excretion.

What About the PURE Study?

Neal: I’d like to get your thoughts on a recent piece of research around this issue of lowering sodium and whether it's good or bad.  Obviously, we’ve heard about the PURE study, and this apparent J- shaped association: where people with high sodium levels have high risk, but also people with low sodium have a higher risk for cardiovascular disease.

There was a recent re analysis from the Trials of Hypertension Project where they tried to understand why this might be happening. The key issue raised with the PURE study is that it doesn't use a 24 hour measured sodium excretion, it uses an estimate based on spot urine, where you basically take an equation that includes height, weight, age, and a number of other things, and you estimate the 24 hr sodium excretion, and then you associate that with risk.

Now, myself and others have been a bit critical about that because effectively, what you're doing is creating a risk score of which sodium is a little bit and then saying that it's the sodium that's driving that association. In this new analysis, they estimated the association with the 24 hour measure and they saw a linear association, so no, J-shape. Then they estimated just using the spot urine and the equations, and they showed that you got this J-shape association. Do you think that clears up the question about the PURE study?

Burnier: I don't know if it will clear up the controversy, but it's a very good point. When you use the calculation, they use a ratio of sodium over creatinine. And of course, the major issue for those with high mortality and low sodium concentration, I am deliberately saying concentration and not low sodium intake, is whether this low sodium concentration really reflects the sodium intake or are there other factors. Creatinine is an indicator of muscle mass and of your health. If you are malnourished you will have low creatinine and this may contribute to the mortality rate, but it has nothing to do with your salt intake. This indirect measurement may just reflect that people are not in a very good shape.

I loved this analysis because they took the data from the top trials and showed that you can actually change the format of the relationship depending on how you calculate the sodium concentration. the Trials of Hypertension Project used several measurements of 24 hour urine. This is an important point, because in PURE they used  one measurement that was not really standardized to assess risk.

Potassium and Hyperkalemia

Neal: Can I ask you about potassium because there’s been a lot of concern about potentially increasing the risk of hypokalemia in patients, Do you think that's a real issue?

Burnier: This is an issue in patient with chronic kidney disease (CKD)

Neal: Severe CKD or any level?

Burnier: Largely for people with an eGFR <30 ml/min/1.73m2 with stage3b or stage 4 CKD. Otherwise I think there is absolutely no risk of hyperkalemia. If you eat a banana one day you will also get more potassium, but a lot of the potassium we eat is excreted. I don't think there’s any risk for the general population.

Neal: What do you think the Peruvian study will mean for the use of salt substitute? Doyou think we’re going to see it used a lot more, or do you think we still need more research?

Burnier: I think we still need more research. There are ongoing studies but a lot of them are in China, in elderly homes. Some studies from China were very positive and showed a benefit, but some were negative. They're still some controversy and I think it would be good to have some studies outside China maybe from Australia or in Europe.

But it's difficult. For example, in Switzerland we wanted to replace some of the sodium with more potassium but the authorities didn't want that because they would prefer to decrease the appetite for salt. That is a very difficult thing to do. And I'm not sure we can get there.

Neal: I want to finish by talking briefly about some ongoing research. We have the SSASS study going on in China. It’s 21,000 people randomized to salt substitute or usual. We're just starting the final follow up after five years intervention and in about 12 months time I hope to be able to come and talk about it. We’re looking at the effects of a salt substitute on stroke.

So I think I'll leave it there. Thanks very much for listening. And Michel, thanks very much for sharing.

 

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