Serum Chloride Is an Independent Predictor of Mortality in Hypertensive Patients

<jats:p> Chloride (Cl <jats:sup>−</jats:sup> ) is the major extracellular anion in the body, accompanying sodium (Na <jats:sup>+</jats:sup> ), and is primarily derived from dietary sources. Data suggest that increased dietary Cl <jats:sup>−</jats:sup> intake increases blood pressure, yet paradoxically, higher serum Cl <jats:sup>−</jats:sup> appears associated with lower mortality and cardiovascular risk. This implies that serum Cl <jats:sup>−</jats:sup> also reflects risk pathways independent of blood pressure, serum Na <jats:sup>+</jats:sup> , and bicarbonate (HCO <jats:sub>3</jats:sub> <jats:sup>−</jats:sup> ). We analyzed 12 968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl <jats:sup>−</jats:sup> was an independent predictor of mortality. To distinguish the effect of Cl <jats:sup>−</jats:sup> from Na <jats:sup>+</jats:sup> and HCO <jats:sub>3</jats:sub> <jats:sup>−</jats:sup> , we adjusted for these electrolytes and also performed the analysis stratified by Na <jats:sup>+</jats:sup> /HCO <jats:sub>3</jats:sub> <jats:sup>−</jats:sup> and Cl <jats:sup>−</jats:sup> levels. Generalized estimating equation was used to determine the effect of baseline Cl <jats:sup>−</jats:sup> on follow-up blood pressure. The total time at risk was 197 101 person-years. The lowest quintile of serum Cl <jats:sup>−</jats:sup> (<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 <jats:sup>−</jats:sup> 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 <jats:sup>+</jats:sup> , K <jats:sup>+</jats:sup> , and HCO3 <jats:sup>−</jats:sup> levels. The group with Na <jats:sup>+</jats:sup> >135 and Cl <jats:sup>−</jats:sup> >100 had the best survival, and compared with this group, the Na <jats:sup>+</jats:sup> >135 and Cl <jats:sup>−</jats:sup> <100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11–1.31). Low, not high Serum Cl <jats:sup>−</jats:sup> (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl <jats:sup>−</jats:sup> and risk. </jats:p>