Serum chloride as a novel marker for adding prognostic information of mortality in chronic heart failure

Background: Serum chloride concentrations have clinical significance in the prognosis of heart failure (HF). Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF). This study sought to investigate the prognostic ability of admission serum chloride for long-term mortality in CHF patients. Methods: We identified 1021 consecutive patients diagnosed with CHF. Participants were followed up for all-cause mortality at 21 +/- 9 months to establish the survival models and analyze the association between admission serum chloride concentrations and death risk. Results: Of the 1021 patients, 905(88.6%) available cases were obtained. Admission serum chloride concentrations of patients were independently and inversely associated with long-term mortality (hazard ratio [HR]: 0.890; 95% CI: 0.863 to 0.918; p < 0.001). After multivariable risk adjustment for age, male sex, history of diabetes, LVEF, loop diuretic use, beta-blocker use, ACEI or ARB use, eGFR and NT-proBNP, chloride concentrations remained independently associated with mortality (HR:0.922; 95% CI:0.887 to 0.958; p < 0.001) but not independent of sodium concentrations (HR: 0.953; 95% CI: 0.900 to 1.009; p = 0.095). The optimal cutoff value of chloride concentrations predicting death was 102.8 mmol/l with an area under the curve (AUC) value of 0.686 (95% CI: 0.635 to 0.737; p < 0.001), with a sensitivity of 62% and specificity of 70%. The lower chloride concentrations could significantly increase the risk ratio of CHF patients in the setting of hyponatremia (p < 0.001). The cumulative survival estimates significantly differed across Na/Cl quartiles (log-rank chi(2) 19.14, p < 0.001), with higher mortality for higher Na/Cl ratio. Correlation analysis showed a positive correlation between serum chloride concentrations and sodium concentrations (r = 0.598; p < 0.001). An increased AUC was observed by combining chloride and sodium (AUC = 0.704, 95% CI:0.655-0.754, p < 0.001) compared to sodium only (AUC = 0.689, 95% CI:0.639-0.739, p < 0.001). Conclusions: In a Chinese Han population, admission serum chloride concentrations are inversely associated with all-cause mortality of CHF patients and provide incremental prognostic information of serum sodium.