Synergistic Effects of Normal-Range Serum Sodium and Potassium on Mortality: The Modifying Role of Inflammation From...

This study aimed to investigate the associations of serum sodium and potassium levels within the normal range with cardiovascular (CV) and all-cause mortality, and to further explore the potential roles of oxidative stress and inflammatory biomarkers in these associations.

We analyzed NHANES 1999-2018 data from 32,837 adults with normal baseline serum sodium (135-146 mmol/L) and potassium (3.5-5.0 mmol/L), stratified by tertiles. Weighted Cox models assessed associations with CV and all-cause mortality, and bootstrap-based causal mediation analysis assessed nine oxidative stress and inflammatory biomarkers.

The lowest tertile of serum sodium was associated with an increased risk of all-cause mortality (HR: 1.17; 95% CI: 1.03-1.32; p = 0.017), while the highest tertile of serum potassium was associated with an increased risk of CV (HR: 1.26; 95% CI: 1.00-1.58; p = 0.052) and all-cause mortality (HR: 1.14; 95% CI: 1.02-1.29; p = 0.025). Serum sodium and potassium showed a statistically significant interaction for all-cause mortality (p = 0.044), with the lowest risk at sodium 138-139 mmol/L and potassium 3.5-3.8 mmol/L (HR: 0.46, 95% CI: 0.31-0.68; p < 0.001). Mediation analysis showed that inflammatory biomarkers accounted for 0.8% to 1.5% of the associations between serum sodium/potassium and CV or all-cause mortality.

In the general population, lower normal-range serum sodium was associated with higher all-cause mortality, while higher serum potassium was linked to increased cardiovascular and all-cause mortality. Inflammatory biomarkers may partially mediate these associations. Our findings provide more evidence that the "safest" sodium and potassium interval needs to be reconsidered.