Association of serum osmolality with all-cause and cardiovascular mortality in US adults: A prospective cohort study

The association between serum osmolality, an effective indicator of body hydration status, and long-term mortality in the general population remains undetermined. The present study aimed to investigate the association of serum osmolality with long-term all-cause and cardiovascular mortality among adults in the United States.This cohort study used data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Participants were linked to National Death Index mortality data from the survey date through December 31, 2019. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs, and restricted cubic spline (RCS) regression was conducted. A total of 18312 US adults were included. During a median follow-up of 8.7 years, 1353 total deaths occurred, including 379 cardiovascular deaths. After multivariable adjustments, compared with the 3rd quartile (Q3) of serum osmolality, participants in the 1st (Q1) and 4th (Q4) quartiles were at a significantly higher risk of all-cause mortality (HR 1.41 [95% CI, 1.14-1.75] and 1.29 [95% CI, 1.04-1.61], respectively). RCS revealed a nonlinear relationship of serum osmolality to all-cause and cardiovascular mortality, with an inflection point of 278 mmol/kg.In the nationally representative cohort of US adults, serum osmolality was nonlinearly associated with all-cause and cardiovascular mortality. The risk of mortality was lowest around an osmolality of 278 mmol/kg. These findings suggest the importance of serum osmolality management for long-term health outcomes.