Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events

Study Questions:

What is the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular (CV) events in patients with established CV disease or diabetes mellitus?

Methods:

This was an observational analysis of two cohorts (N = 28,880) included in the ONTARGET and TRANSCEND trials (November 2001-March 2008 from initial recruitment to final follow-up). The investigators estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample (Kawasaki formula). They used restricted cubic spline plots to describe the association between sodium and potassium excretion and CV events and mortality, and to identify reference categories for sodium and potassium excretion. Investigators used Cox proportional hazards multivariable models to determine the association of urinary sodium and potassium with CV events and mortality. The main outcome measures were CV death, myocardial infarction (MI), stroke, and hospitalization for congestive heart failure (CHF).

Results:

At baseline, the mean (standard deviation [SD]) estimated 24-hour excretion for sodium was 4.77 g (1.61); and for potassium was 2.19 g (0.57). After a median follow-up of 56 months, the composite outcome occurred in 4,729 (16.4%) participants, including 2,057 CV deaths, 1,412 with MI, 1,282 with stroke, and 1,213 with hospitalization for CHF. Compared with the reference group with estimated baseline sodium excretion of 4-5.99 g/day (n = 14,156; 6.3% participants with CV death, 4.6% with MI, 4.2% with stroke, and 3.8% admitted to the hospital with CHF), higher baseline sodium excretion was associated with an increased risk of CV death (9.7% for 7-8 g/day; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.26-1.86; and 11.2% for >8 g/day; HR, 1.66; 95% CI, 1.31-2.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for >8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for >8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.12-2.05 for >8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for <2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of <1.5 g/day (n = 2,194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for >3 g/day) on multivariable analysis.

Conclusions:

The authors concluded that the association between estimated sodium excretion and CV events was J-shaped, and higher estimated potassium excretion was associated with a reduced risk of stroke.

Perspective:

This study reports a J-shaped association between estimated sodium excretion and CV events. Compared with baseline sodium excretion of 4-5.99 g/day, sodium excretion of more than 7 g/day was associated with an increased risk of all CV events, whereas a sodium excretion of <3 g/day was associated with increased risk of CV mortality and hospitalization for CHF. There was an association between higher estimated potassium excretion and reduction in stroke risk, but no evidence of interaction between sodium and potassium excretion for any outcome. The study highlights the need for additional studies to understand optimal sodium intake in those at increased CV risk, and use of potassium as a potential intervention for stroke prevention. Given the intrinsic weakness of observational studies in this area, the inferences that can be drawn from the current analyses are limited, and at this time, clinicians should not deviate from the current recommendations of reducing the exposure to dietary sodium in the general population.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Myocardial Infarction, Potassium, Stroke, Sodium, Heart Failure, Cardiovascular Diseases


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