Serum Chloride Is an Independent Predictor of Mortality in Hypertensive Patients
Chloride (Cl−) is the major extracellular anion in the body, accompanying sodium (Na+), and is primarily derived from dietary sources. Data suggest that increased dietary Cl− intake increases blood pressure, yet paradoxically, higher serum Cl− appears associated with lower mortality and cardiovascular risk. This implies that serum Cl− also reflects risk pathways independent of blood pressure, serum Na+, and bicarbonate (HCO3−). We analyzed 12 968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl− was an independent predictor of mortality. To distinguish the effect of Cl− from Na+ and HCO3−, we adjusted for these electrolytes and also performed the analysis stratified by Na+/HCO3− and Cl− levels. Generalized estimating equation was used to determine the effect of baseline Cl− on follow-up blood pressure. The total time at risk was 197 101 person-years. The lowest quintile of serum Cl− (<100 mEq/L) was associated with a 20% higher mortality (all-cause, cardiovascular and noncardiovascular) compared with the remainder of the subjects. A 1 mEq/L increase in serum Cl− was associated with a 1.5% (hazard ratio, 0.985; 95% confidence interval, 0.98–0.99) reduction in all-cause mortality, after adjustment for baseline confounding variables and Na+, K+, and HCO3− levels. The group with Na+>135 and Cl−>100 had the best survival, and compared with this group, the Na+>135 and Cl−<100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11–1.31). Low, not high Serum Cl− (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl− and risk.
- Received May 30, 2013.
- Revision received June 18, 2013.
- Accepted August 2, 2013.
- © 2013 American Heart Association, Inc.