Serum Chloride Is an Independent Predictor of Mortality in Hypertensive Patients

Abstract

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 (HCO 3 − ). 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 HCO 3 − , we adjusted for these electrolytes and also performed the analysis stratified by Na + /HCO 3 − 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.