Risk of Cardiovascular Mortality Associated With Serum Sodium and Chloride in the General Population

The prognostic value of serum chloride among patients with heart failure was demonstrated by previous studies. However, the association of serum chloride and risk of cardiovascular mortality among the general population remains unclear.

We included 16,483 participants in National Health and Nutrition Examination Survey III. Cox proportional hazards models were used to assess the association of serum sodium and chloride and cardiovascular mortality. Potential confounders were included in the models. Levels of serum sodium and chloride were also modeled with restrictive cubic splines for potential nonlinear associations. Subgroup analyses were based on baseline diseases and use of diuretics.

The mean age was 43.5 years, and 47.8% of the participants were men. During 277,059 person-years of follow-up, there were 1714 cardiovascular deaths. In the multivariate model, low-level serum sodium was associated with an increased risk of cardiovascular mortality (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.02-1.18 per standard deviation [SD]; P = 0.009), whereas a lower level of serum chloride was not (HR, 1.04; 95% CI, 0.97-1.12 per standard deviation; P = 0.278). Analyses with restrictive cubic splines yielded similar results.

Low serum sodium, rather than chloride, was independently associated with an increased risk of cardiovascular mortality.