Relationship of serum sodium concentration to mortality in a wide spectrum of heart failure patients with preserved and with reduced ejection fraction: an individual patient data meta-analysis

Hyponatraemia has been associated with reduced survival in patients with heart failure and reduced ejection fraction (HF-REF). The relationship between serum sodium and outcome is unclear in heart failure with preserved (epsilon 50) ejection fraction (HF-PEF). Therefore, we used a large individual patient data meta-analysis to study the risk of death associated with hyponatraemia in HF-REF and in HF-PEF. This analysis included 14 766 patients from 22 studies that recruited patients without ejection fraction inclusion criterion at baseline and reported death from any cause. Cox proportional analysis was undertaken for hyponatraemia (sodium 135 mmol/L), adjusted for variables of clinical relevance, and stratified by study. The endpoint was death from any cause at 3 years. Patients with hyponatraemia (n 1618) and patients with normal serum sodium had similar characteristics as regards to age, gender, and ischaemic aetiology. However, patients with hyponatraemia had higher New York Heart Association class and lower blood pressure. At follow-up, there were 335 deaths among 1618 patients with hyponatraemia (21) and 2128 deaths among 13 148 patients with normal serum sodium (16). The risk of death appeared to increase linearly with serum sodium levels 140 mmol/L. Hyponatraemia was identified in 1199 HF-REF patients (11) and 419 HF-PEF patients (11). Hyponatraemia was independently predictive of death in both HF-REF [adjusted hazard ratio (HR) 1.69, 95 confidence interval (CI) 1.501.91] and HF-PEF (adjusted HR 1.40, 95 CI 1.101.79, P for interaction 0.20). Hyponatraemia is a powerful determinant of mortality in patients with HF regardless of ejection fraction. Further work is needed to determine if correction of hyponatraemia translates into clinical benefit.