Study Reopens Rift Over Merits of Low-Sodium-for-All Public-Health Policies

Patrice Wendling

May 27, 2016

HAMILTON, ON — A pooled analysis involving more than 130,000 people from 49 countries adds to a growing body of evidence that low sodium intake may be harmful, but acceptance is far from universal[1].

Compared with average sodium intake (3 to 6 g/day), low sodium intake (<3 g/day) was associated with an increased risk of cardiovascular events and death regardless of whether the patient had hypertension or not.

In contrast, high sodium intake (>6 g/day) was associated with increased risk only in hypertensive patients, according to the investigators, led by Dr Andrew Mente (McMaster University, Hamilton, ON).

"The message is that populationwide sodium reduction is probably ill-advised, and we need to simply identify the individuals who have both hypertension and consume high amounts of sodium and get them to reduce their sodium intake to moderate levels. That would be the ideal approach," Mente told heartwire from Medscape, noting that only about 10% of the population had hypertension and high sodium intake.

Reversing Progress

The study prompted a swift response when published online May 20, 2016 in the Lancet. In a statement, American Heart Association (AHA) president Dr Mark Creager (Dartmouth-Hitchcock Medical Center, Lebanon, NH) expressed concern that adopting the authors' recommendation "may reverse the progress that has occurred in modifying dietary sodium intake and reducing the risk of high blood pressure and its effect on heart disease and stroke."

Immediate AHA past-president Dr Elliott Antman (Brigham & Women's Hospital, Boston, MA) said the study should be "disregarded" and criticized its use of a single urine test to assess sodium intake. "This is a flawed study, and you shouldn't use it to inform yourself about how you're going to eat. The AHA has reviewed the totality of the evidence and we continue to maintain that no more than 1500 mg of sodium a day is best for ideal heart health."

Anticipating this criticism, the authors pointed out that use of one overnight urine sample has been validated against the gold standard of 24-hour urine collections in prior studies in healthy individuals and hypertensives as well as in their own international validation study. The analyses also adjusted for day-to-day variability.

Although the investigators used group-level measures of intake in estimating sodium intake, this cannot resolve all problems related to the use of a less precise method, Dr Guy De Backer (Ghent University, Belgium) told heartwire . He also expressed surprise that the lowest category of sodium intake had an upper cut point of <3 g, which makes it "impossible" to examine the association between very low (<3 g/day), low (3–5 g/day), and higher intakes with CVD and total mortality.

"Altogether my view is that this study is of interest to researchers but has little impact on public health in Europe," he said. "The conclusion that salt-intake reduction should be recommended only to individuals with hypertension and a high dietary salt intake is in my view not acceptable to European communities, where the actual salt intake is on average between 8 and 10 g/day."

The analysis included 133,118 participants (median age 55 years) drawn from four prospective studies: ONTARGET, TRANSCEND, EPIDREAM, and the ongoing PURE. The latter provided the bulk of the subjects and reported that higher and lower levels of sodium excretion are associated with increased risk of death and cardiovascular events.

The present results are also in keeping with the recent PREVEND study[2] and a meta-analysis[3] also showing a U-shaped association between sodium intake and cardiovascular events.

Entrenched Thinking

"Whenever you have a paradigm shift, it's normal that there is resistance and not to have everyone come on board initially," Mente said. "You look at trans-fat back in the 1980s and there was quite a bit of data coming out by a number of investigators that trans-fat was actually harmful, but people dismissed the findings."

He said the various organizations that push for low sodium believe the trials that show lowering sodium reduces blood pressure and therefore that reducing blood pressure reduces CVD. But, "It's not quite that simple. The body is more complicated than that."

Increasing data show that reducing sodium to low levels activates the renin-angiotensin system, catecholamines, and aldosterone, which are associated with increased CVD events and mortality. "If you look at most other essential nutrients that the body needs, not just sodium, they all have a U-shaped relationship with health measures, so you wouldn't expect sodium to be any different."

Also, the associations between sodium intake and the composite end point were unchanged after further adjustment for baseline blood-pressure levels, indicating mechanisms unrelated to blood pressure.

In an editorial that accompanied the study[4], Dr Eoin O'Brien (University College Dublin, Ireland) writes, "Given the dependency of so many physiological systems on the sodium cation, it should come as no surprise that a low-salt-for-all policy would benefit some and disadvantage others. So rather than allowing contrary evidence to dispel the positive efforts that have been made to reduce the salt content of foods, we must now direct our efforts to formulating a policy that will benefit the majority in society without compromising the minority."

Randomized Data

Past AHA and American Society of Hypertension president Dr Suzanne Oparil (University of Alabama at Birmingham) told heartwire that the pooled analysis provides "more evidence that low sodium intake is harmful."

Critics who argue that salt intake can't really be measured accurately in population studies have a point, she said, but added that even when the PURE investigators validated their methods, the validation was criticized.

The current backlash is more of the same. "It's a defensive response. They don't want to believe it because it's totally contrary to what they've been telling everyone."

PREVEND author Dr Michel Joosten (University Medical Center Groningen, the Netherlands) told heartwire that the pooled analysis is consistent with PURE and observational analyses reported by coauthor Dr Martin O'Donnell (National University of Ireland Galway)[5], "which makes it a more compelling case," but that all three studies had a relatively short follow-up of around 4 years, "which may have been too short to develop hypertension and subsequent cardiovascular diseases or death."

Still, pushing sodium intake too low will most likely have detrimental health effects. The question remains, however, what is too low? "Personally, I do think it is lower than the 3 g of sodium (7.5 g of salt) per day as suggested by the research of Mente and O'Donnell. Having said that, I also think we should at least be open to all available evidence and keep an open mind about the topic. Perhaps we can go too low as far as sodium reduction is concerned in the general population."

Joosten, Oparil, and O'Brien suggest that the issue of sodium reduction may only be resolved by conducting a randomized controlled trial. As a prelude to such a large definitive study, the investigators have initiated the pilot Sodium Intake in Chronic Kidney Disease (STICK) randomized trial comparing usual care vs counseling targeting a sodium intake of <2.3 g/day. The estimated completion date is March 2018.

The authors and O'Brien report no relevant financial relationships; Mente is a recipient of a research early career award from Hamilton Health Sciences Foundation. Other information for the coauthors is listed in the article.

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