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A b s t r a c tBackground: 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 × 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: 1 st % = 280 ± 6, 2 nd % = 288 ± 1, 3 rd % = 293 ± 2 (95% confidence interval [CI] 292.72-293.3), and 4 th % = 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 1 st quartile having the worst prognosis, followed by the 4 th quartile and the 2 nd quartile, while the 3 rd 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.

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