Plasma osmolality predicts mortality in patients with heart failure with reduced ejection fraction

Background: Heart failure (HF) is a fatal disease. Plasma osmolality with individual impacts of sodium, blood urea nitrogen (BUN), and glucose has not been studied prognostically in patients with HF. Aim: This study aims to investigate the impact of serum osmolality on clinical endpoints in HF patients. Methods: A total of 509 patients (383 males, 126 females) with HF with reduced ejection fraction in three HF centres were retrospectively analysed between January 2007 and December 2013. Follow-up data were completed for 496 patients. Plasma osmolality was calculated as (2 x Na) + (BUN/2.8) + (Glucose/18). Quartiles of plasma osmolality were produced, and the possible relationship between plasma osmolality and cardiovascular mortality was investigated. Results: The mean follow-up was 25 +/- 22 months. The mean age was 56.5 +/- 17.3 years with a mean EF of 26 +/- 8%. The mean levels of plasma osmolality were as follows in the quartiles: 1st % = 280 +/- 6, 2nd % = 288 +/- 1, 3rd % = 293 +/- 2 (95% confidence interval [ CI] 292.72-293.3), and 4th % = 301 +/- 5 mOsm/kg. The EF and B-type natriuretic peptide levels were similar in the four quartiles. Univariate and multivariate analyses in the Cox proportional hazard model revealed a significantly higher rate of mortality in the patients with hypo-osmolality. The Kaplan-Meier plot showed graded mortality curves with the 1st quartile having the worst prognosis, followed by the 4th quartile and the 2nd quartile, while the 3rd quartile was shown to have the best prognosis. Conclusions: Our study results suggest that normal plasma osmolality is between 275 and 295 mOsm/kg. However, being close to the upper limit of normal range (292-293 mOsm/kg) seems to be the optimal plasma osmolality level in terms of cardiovascular prognosis in patients with HF.