Lower serum chloride levels are associated with worse functional status and higher clinical burden in heart failure

Abstract

Background Electrolyte abnormalities are frequent in heart failure (HF) and are closely linked to disease severity and clinical outcomes. Among these, serum chloride has gained attention as a potential integrative marker of neurohormonal activation, volume status, and diuretic responsiveness. Nevertheless, real-world data describing how serum chloride relates to baseline clinical characteristics in HF populations are limited. Purpose To evaluate the association between serum chloride levels and baseline clinical, functional, and comorbidity profiles in patients with heart failure. Methods This cross-sectional study used data from a multicenter HF registry comprising 947 patients. Serum chloride measurements were available in 686 individuals. Patients were categorized into three groups based on serum chloride concentrations, in accordance with established clinical thresholds: hypochloremia (<96 mmol/L), normochloremia (96–105 mmol/L), and hyperchloremia (>105 mmol/L). Baseline demographics, NYHA functional class, comorbidities, prior hospitalization, emergency department admissions, and treatment-related variables were compared across chloride categories. Results Serum chloride levels showed significant associations with markers of disease burden. Patients with lower chloride levels had higher rates of previous HF-related hospitalization (p = 0.002) and emergency department admissions (p = 0.002). A graded relationship was observed between chloride categories and NYHA functional class, with lower chloride levels corresponding to worse functional status (p < 0.001). Lower chloride was also associated with a higher prevalence of diabetes mellitus (p = 0.005), atrial fibrillation (p = 0.007), chronic obstructive pulmonary disease (p = 0.006), anemia (p = 0.002), and malignancy (p = 0.036) (Table 1). No significant associations were identified with sex, smoking, alcohol use, coronary artery disease, or most prior interventional or surgical procedures. Diuretic dose escalation demonstrated a significant linear trend across chloride groups (p = 0.028), indicating greater treatment intensity at lower chloride levels (Table 1, Table 2). Conclusion In this large, contemporary HF cohort, lower serum chloride levels were consistently associated with worse functional status, increased healthcare utilization, and a higher burden of systemic comorbidities. These findings support serum chloride as a clinically meaningful marker of baseline disease complexity in heart failure and underscore the need for prospective studies to clarify its prognostic and therapeutic relevance.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.