Abstract
BACKGROUND: Plasma osmolality has been recognized as a significant predictor of adverse outcomes in heart failure (HF), particularly among patients with hyponatremia. However, its prognostic value remains underexplored in normonatremic HF patients. This study aimed to evaluate the association between osmolality and mortality in HF patients with normal serum sodium in a community setting. METHODS: We analyzed data from 1,157 individuals with HF in the 1999-2014 National Health and Nutrition Examination Survey. The inclusion criteria were (I) a diagnosis of congestive HF, (II) available hydration-related laboratory results (e.g., sodium and potassium), and (III) a normal range of serum sodium (135-146 mmol/L). Using classification and regression tree analysis, participants were stratified into three osmolality groups (<286, 286-295, ≥296 mmol/L). Exposure variables included osmolality, sodium level, water deficit, tonicity, haematocrit level, haematocrit to haemoglobin ratio, and potassium level. Cox proportional hazard regression was used to assess the relationship between these variables and overall mortality, with adjustments made for demographic factors. RESULTS: The mean follow-up time was 69.9 months, and 55.4% of participants were male, with mean age of 67 years. Higher plasma osmolality (≥296 mmol/L) and potassium level (≥4.9 mmol/L) were independently associated with increased overall mortality [osmolality: hazard ratio (HR) 2.36, 95% confidence interval (CI): 1.49-3.70, P<0.001; potassium: HR 1.71, 95% CI: 1.28-2.30, P<0.001]. Conversely, higher haematocrit level (≥35%) was linked to lower mortality (HR 0.36, 95% CI: 0.21-0.62; P<0.001). CONCLUSIONS: In a community setting of HF population, higher plasma osmolality (≥296 mmol/L) is an independent prognostic factor of poor prognosis in patients with HF and a normal serum sodium level. Plasma osmolality should be considered for integration into routine risk stratification for normonatremic HF individuals.