High and Low Levels of Sodium Intake Track With CV Risk

Shelley Wood

November 22, 2011

November 22, 2011 (Chicago, Illinois) — Adding another dash of controversy to the ongoing debate over the health benefits of restricting sodium intake, a new study has found that CV risk was increased at both low and high levels of sodium intake [1].

The new analysis, examining the association between estimated sodium excretion and cardiovascular events among almost 29 000 adults, showed not only that CV risk was increased among those with the lowest levels of sodium excretion, but also that risk associated with high levels of intake appeared only at sodium intake levels much higher than the cutoffs currently recommended in nutritional guidelines.

But far from muddying the waters, Dr Martin O'Donnell (McMaster University, Hamilton, UK) and colleagues--including a number of prominent hypertension researchers--say their findings should actually dispel some confusion.

"On the face of it, it looks like studies are meeting different and convergent findings," O'Donnell told heartwire . "We believe our study helps clarify the situation and provides the best description of the association between sodium intake and CVD. If you look back at previous epidemiological studies, some were positive, some found no association, and more recently some have found an inverse association between sodium intake and CVD risk. We feel that is largely explained by the J-curve we observed."

The study results are published in the November 23, 2011 issue of the Journal of the American Medical Association.

Different and Convergent Findings Explained?

Of note, however, the authors did not observe a significant association until sodium excretion exceeded 6.5 g per day, "a threshold that is higher than that recommended by the WHO and many national guidelines," the authors write.

As a crude estimate, "sodium out" is believed to reflect "sodium in," O'Donnell told heartwire , such that excretion levels of 6.5 g per day are roughly equal to consuming 6500 mg daily.

"Compared with moderate sodium excretion, we found an association between high sodium excretion and CV events and low sodium excretion and CVD events, which emphasizes the urgent need to establish a safe range for sodium intake in randomized controlled trials," they observe.

Most nutrition guidelines, notes Dr Paul Whelton (Tulane University, New Orleans, LA) in an accompanying editorial, recommend sodium intake of no higher than 1500 mg for people with established hypertension and no higher than 2300 mg for those at lower risk [2].

"The general body of knowledge suggesting that we take in amounts of sodium that are vastly in excess of our needs is exceedingly solid," he said in an interview. "It's good to publish findings, it adds to the puzzle, and it's an interesting study, but one has to be cautious," he said.

The Low and the High and the in-Between

O'Donnell and colleagues, used single baseline urine tests obtained in the ONTARGET and TRANSCEND trials, measuring both sodium and potassium excretion, and linked these results with subsequent CVD deaths, MIs, and congestive heart failure hospitalizations over 56 months of follow-up.

They report that compared with mean levels of sodium excretion from 4 to 5.99 g per day, subjects with sodium excretion greater than 7 g per day faced an increased risk of CV events, but so did subjects with excretion levels of less than 3 g per day.

Hazard Ratios (95% CI) According to Sodium Excretion, Compared With Mean Excretion in This Population (4–5.99 G/Day)*

Outcome <2 g/d 2–2.99 g/d 6–6.99 g/d 7–8 g/d >8 g/d
All CV events 1.21 (1.03–1.43) 1.16 (1.04–1.28) 1.09 (0.99–1.20) 1.15 (1.00–1.32) 1.49 (1.28–1.75
CV death 1.37 (1.09–1.73) 1.19 (1.02–1.39) 1.11 (0.96–1.29) 1.53 (1.26–1.86) 1.66 (1.31–2.10)
Stroke 1.06 (0.76–1.46) 1.05 (0.86–1.28) 0.95 (0.79–1.15) 1.06 (0.81–1.40) 1.48 (1.09–2.01)

*After multivariate analysis

To heartwire , O'Donnell acknowledged that the lowest sodium excretion group in this analysis--where risk of CV events appeared to be increased by 20%--was a range reflecting intake levels recommended in most guidelines.

"But the primary finding is the observed association between high sodium intake and CVD across all the CV outcomes that were measured," he stressed. "That underpins current strategies of reducing sodium intake in people who are consuming high-sodium diets. Also, because sodium intake certainly in North America and Europe is from nondiscretionary sources and a lot of manufactured foods are high in sodium, the current efforts to reduce sodium in those foods are certainly consistent with our findings."

Whelton, for his part, said: "I wouldn't put too much weight on this at all."

He points to the observational nature of the findings, the fact that they were drawn from two studies not originally intended for the purpose of linking sodium intake to CV outcomes, and that fact that sodium intake is estimated based on one-time measurements of urinary sodium excretion.

Moreover, the J-curve, as well as in other areas of medicine where it has been seen, tends to be "strongest" on the long end of the J, where there are large numbers of people and the highest risk of events. On the short end of the tail, where there are fewer people and fewer events, "It's very shaky down there," Whelton said. "Those are often unusual people, often very sick people, and because they are sick they change their diet or are advised to change their diet. So you have to interpret that with a lot of caution."

Where O'Donnell and Whelton agree is on the urgent need for outcomes trials of sodium restriction.

"There are definite challenges and logistical obstacles to conducting such a study, but the public-health importance of this question mandates that every effort is made to do so," O'Donnell told heartwire .

O'Donnell would not say whether he thought nutritional recommendations are using cut points that are too low (or potentially harmful) and said that he himself tries to reduce the sodium in his diet as part of an overall healthy diet. "I think we must base all our decision on diets on the best available evidence, and obviously that can change over time."

Potassium Findings Also Warrant a Closer Look

And while much of the academic and media attention given to this analysis will likely focus on the sodium findings, the study also addressed the link between potassium excretion and CV events,

"This may be lost in the discussion on sodium, but we found an association between increased potassium urinary excretion . . . and a reduced risk of stroke," O'Donnell noted. "This is another area that certainly merits further research to see if supplementation of potassium can reduce CVD, particularly stroke."


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