But Dr Cook maintained that the long-term analyses of TOHP provide strong evidence for a linear relationship. “In TOHP, we used very well-characterized measures of usual sodium intake, which are more precise than the methods used in other studies,” she noted. TOHP assessed sodium intake using 24-hour urinary sodium excretion, which is considered the gold standard, at multiple time points per patient. In contrast, other studies examining sodium and clinical outcomes measured sodium intake with questionnaires, food diaries, and urine spot samples, which are prone to error and bias.1

“We feel the that analyses using TOHP data can provide estimates that are more accurate and less prone to bias,” Dr Cook stated. “Therefore, we can conclude that decreasing sodium intake to the lowest levels seems to confer benefits for mortality as well as CVD, although the lowest levels can be difficult to achieve.”

However, Dr Mente argued that the 20-year TOHP mortality analysis does not demonstrate that low sodium intake is beneficial compared with average sodium consumption in the population. “There is currently no evidence from any study, including the TOHP studies, that low sodium intake at the currently recommended level of 2.3 grams per day is better than moderate sodium intake at 3 to 5 grams per day in reducing CVD or mortality. In fact, the totality of the data shows that moderate levels of sodium intake are optimal,” he said.


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Dr Mente offered an explanation for why moderate sodium intake may be ideal. “The underlying biological explanation for why very low sodium intake may be detrimental is that going below a certain level may activate hormonal systems like the renin-angiotensin system, which we know from previous studies is associated with harm,” he said. “Moderate levels of sodium intake may strike the right balance between lowering blood pressure while avoiding the harmful effects of activating the renin-angiotensin system.”

The Take-Away

In light of the controversy surrounding the relationship between low sodium intake and clinical outcomes, what conclusions can be drawn from this analysis of long-term mortality in TOHP?

Dr Cook and colleagues found that higher levels of dietary sodium intake correlated with increased mortality. They also concluded that lower sodium intake is associated with better outcomes, based on the linear relationship observed in this and other studies.1 According to Dr Cook, “These findings support the recommendations of the AHA and US Dietary Guidelines to lower dietary sodium intake, as well as the recent draft guidance from the FDA regarding sodium reduction in processed foods.”

Dr Mente also concurred that sodium intake should be reduced among individuals whose diets are high in sodium. “Everybody agrees high levels of sodium are harmful,” Dr Mente said. “What is less clear is: what is high?”

He pointed out that a clear benefit of low vs moderate sodium intake in reducing CV events or mortality—without unintended consequences—needs to be demonstrated before making population-wide recommendations. “For this, there is a need for large, randomized controlled trials with long-term clinical outcomes,” he stated.

Ultimately, Dr Mente recommended consuming a balanced diet as a lifestyle measure to improve long-term clinical outcomes. “If you eat an all-around healthy diet high in fruits and vegetables, and minimize processed and sugary foods, you don’t need to worry about single nutrients like sodium,” he said.

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Disclosures: TOHP was funded by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute. TOHP Followup Study was supported by grants from the NHLBI American Heart Association. Drs Cook and Mente as well as the authors of the current study report no relevant disclosures.

References

  1. Cook NR, Appel LJ, Whelton PK. Sodium intake and all-cause mortality over 20 years in the trials of hypertension prevention. J Am Coll Cardiol. 2016;68(15):1609-1617. doi: 10.1016/j.jacc.2016.07.745.
  2. Mente A, O’Donnell MJ, Yusuf S. How robust is the evidence for recommending very low salt intake in entire populations? J Am Coll Cardiol. 2016;68(15):1618-1619. doi:10.1016/j.jacc.2016.08.008.
  3. Appel LJ, Frohlich ED, Hall JE, et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011;123(10):1138-1143. doi: 10.1161/CIR.0b013e31820d0793.
  4. Sacks FM, Svetkey LP, Vollmer WM, et al; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3-10.
  5. Trials of Hypertension Prevention Collaborative Research Group. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, phase 1. JAMA. 1992;267:1213–1220.
  6. Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase 2. The Trials of Hypertension Prevention Collaborative Research Group. Arch Intern Med. 1997;157:657–667.

This article originally appeared on The Cardiology Advisor