Abnormal levels of urinary sodium excretion increase CV event risk

Issue: January 2012

An analysis of ONTARGET and TRANSCEND trials showed that high and low sodium excretion, as compared with moderate excretion, increased the risk for CV events, death and hospitalization for congestive HF.

In addition, higher estimated urinary potassium excretion was associated with a reduced risk for stroke.

According to Martin J. O’Donnell, MB, PhD, and colleagues, these data “emphasize the urgent need to establish a safe range for sodium intake in randomized controlled trials.”

The researchers examined the association between sodium and potassium excretion and CV events and mortality. The study was an observational analysis of two cohorts comprising more than 28,000 patients from the ONTARGET and TRANSCEND trials (conducted from November 2001 to March 2008).

At study entry, the average estimated 24-hour excretion was 4.77 g for sodium and 2.19 g for potassium. After a mean follow-up of 56 months, the composite outcome occurred in 4,729 (16.4%) of participants, including 2,057 CV deaths, 1,412 MI, 1,282 strokes and 1,213 hospitalizations for CHF.

Increased risk for CV death was associated with higher baseline sodium excretions of 7 g/day to 8 g/day (9.7%; HR=1.53; 95% CI, 1.26-1.86) and more than 8 g/day (11.2%; HR=1.66; 95% CI, 1.31-2.10) when compared with a reference group with levels of 4 g/day to 5.99 g/day. Higher levels were also linked to a higher risk for stroke (6.6% for >8 g/day; HR=1.48; 95% CI, 1.09-2.01) and hospitalization for CHF (6.5% for >8 g/day; HR=1.51; 95% CI, 1.12-2.05).

At the other end, lower levels of sodium excretion of 2 g/day to 2.99 g/day and less than 2 g/day were associated with increased risk for CV death (8.6%; HR=1.19; 95% CI, 1.02-1.39 and 10.5%; HR=1.37; 95% CI, 1.09-1.73, respectively). Risk for CHF hospitalization was also higher in the presence of lower levels (2 g/day to 2.99 g/day; 5.2%; HR=1.23; 95% CI, 1.01-1.49), according to multivariable analysis.

When the researchers examined potassium excretion, higher levels of 1.5 g/day to 1.99 g/day were associated with a reduced risk for stroke (4.7%; HR=0.77; 95% CI, 0.63-0.94). The reduced risk was also present with even higher levels of 2 g/day to 2.49 g/day (4.3%; HR=0.73; 95% CI, 0.59-0.90), 2.5 g/day to 3 g/day (3.9%; HR=0.71; 95% CI, 0.56-0.91) and more than 3 g/day (3.5%; HR=0.68; 95% CI, 0.49-0.92), according to multivariable analysis.

In an accompanying editorial published in The Journal of the American Medical Association, Paul K. Whelton, MD, MB, MSc, of the department of epidemiology at Tulane University School of Public Health and Tropical Medicine, said: “Although there is general agreement that sodium reduction is appropriate for persons with hypertension, there are some questions about applying this recommendation to the remainder of the population. Part of the hesitation appears to be based on reports of metabolic disturbance, inconsistency in the results of observational studies, and a paucity of clinical trials that document the efficacy of sodium reduction as a means to reduce CVD risk.”

Whelton said American adults consume an excess of sodium, most of which is usually added during food processing.

“A progressive reduction in the addition of sodium to food products could represent one of the ‘lifestyle’ changes with the greatest potential for intervention success,” he said “This shift to a more natural diet would concurrently lead to an absolute increase in dietary potassium content and also lead to an improved sodium-potassium ratio, which may be more desirable than change of either electrolyte of its own.”

For more information:

O’Donnell MJ. JAMA. 2011;306:2229-2238.
Whelton PK. JAMA. 2011;306:2262-2264.

Disclosure: The study was supported by Boehringer Ingelheim, and some of the study researchers report a financial interest with the company. Dr. Whelton reports no relevant financial disclosure.

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