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

AIMS: 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 ( 6550%) 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. METHODS AND RESULTS: 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