NEJM Papers Add to Ongoing Salt Debate

By the NEJM Journal Watch Editors

New studies in the New England Journal of Medicine add to the ongoing debate over the relationship among sodium intake, blood pressure, and cardiovascular events.

In the first, investigators used data from international surveys on sodium intake to quantify global intake of sodium according to age, sex, and country. They then developed a model to assess the effects of current sodium intake, compared with a reference of 2.00 g of sodium daily, on cardiovascular mortality. The estimated mean level of global sodium intake in 2010 was 3.95 g daily; mean regional estimates ranged from 2.18 to 5.51 g daily. Nearly 1 in 10 cardiovascular deaths (1.65 million) were attributable to sodium consumption above the reference level. Most of these deaths occurred in low- and middle-income countries, and more than 40% occurred in people younger than 70.

The other study included about 100,000 adults from 18 high- or low-income countries. Using fasting urinary sodium and potassium measurements, researchers estimated daily sodium and potassium excretion — a surrogate for intake.

Key BP findings were as follows:

• Higher daily sodium excretion was associated with significantly higher systolic and diastolic BP; the association was limited to participants whose daily sodium excretion exceeded 3 g.

• Higher daily potassium excretion was associated with significantly lower systolic BP.

• Mean BP of participants with the highest sodium excretion and lowest potassium excretion was 12/5 mm Hg higher than that of participants with the lowest sodium and highest potassium excretion.

Key findings for a primary composite outcome (death or major adverse cardiovascular event) during roughly 3.7 years' follow-up were as follows:

• Sodium excretion >7 g daily was associated with excess risk for the primary outcome compared with sodium excretion of 4 to 6 g daily (odds ratio, 1.15).

• Sodium excretion <3 g daily also was associated with excess risk for the primary outcome (OR, 1.27); thus, highest and lowest sodium intakes both were associated with adverse clinical outcomes (a U-shaped association).

• Adjustment for BP attenuated the association between the primary outcome and high sodium excretion (but not low sodium excretion), suggesting that BP partly mediated the high-sodium finding.

• Low potassium excretion was associated with excess risk for the primary outcome.

Commenting on the first study, NEJM Journal Watch Cardiology's JoAnne Foody said: "These findings highlight the substantial global burden of high sodium intake and support population-based initiatives to reduce dietary sodium. In preventive care, extrapolative analyses such as this also might help clinicians persuade their patients that minimizing sodium consumption according to guideline recommendations can lower their cardiovascular risk."

And commenting on the second, Allan Brett of NEJM Journal Watch General Medicine said: "For some observers, these findings might suggest that a low-sodium, high-potassium diet will lower BP substantially and promote favorable clinical outcomes; however, the study's observational nature precludes strong inferences about causality or the effects of dietary intervention. The U-shaped association between sodium excretion and adverse clinical outcomes has been noted in previous studies and could represent reverse causality if higher-risk patients are more likely to restrict sodium intake. Alternatively, the authors speculate that excessive sodium restriction could promote harm by activating the renin-angiotensin-aldosterone system in vulnerable patients."

Adapted from NEJM Journal Watch Cardiology and NEJM Journal Watch General Medicine