Angelique B.M.C. Savelberg1, Laura Potasso2,3, Romy van der Groef1, Mirjam Christ-Crain2,3, Ewout J. Hoorn4, Julie C. Refardt1-3 on behalf of the HIT study group.
1)Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands.
2)Department of Endocrinology, Diabetology and Metabolism University Hospital Basel, Basel, Switzerland.
3)Department of Clinical Research, University of Basel, Basel, Switzerland.
4)Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Introduction
Hyponatremia is the most common electrolyte disorder in hospitalized patients. While females are more at risk to be hospitalized due to diuretic-induced hyponatremia, males seem to have a higher 1-year mortality risk. Beyond this, sex differences remain underexplored in clinical research.
Aim
To explore the impact of sex on the clinical presentation of hyponatremia, sodium trajectories and outcomes.
Methods
Secondary analysis of a European multi-center randomized controlled trial involving hospitalized hyponatremic patients (plasma sodium <130 mmol/L). Patients were randomized to receive targeted correction of plasma sodium levels, or standard of care. Sodium trajectories were modelled using multivariable linear mixed models adjusted for age, sex and etiology with patient-specific random effects. Mortality and rehospitalization were analyzed with a multivariate cox proportional hazard model.
Results
2173 patients (52.2% female, median age 73 years, median baseline plasma sodium of 127 mmol/L) were analyzed. Males more often had a history of cardiovascular disease and malignancy. Females were more often symptomatic at baseline (RR 1.10, 95%CI 1.06-1.13) and had a slightly lower plasma sodium over the entire trajectory (-0.41 mmol/L, p=0.003). Female sex was independently associated with 30-day mortality (HR 0.55, 95%CI 0.40 – 0.75) and rehospitalization (HR 0.76, 95%CI 0.60-0.97). Similarly, there was an independent association between a hypervolemic etiology and mortality (HR 2.20, 95%CI 1.16-4.19).
Conclusion
While having lower sodium levels and reporting more often symptoms, females had a lower hazard for mortality and rehospitalization. This raises the question of whether a sex-specific mechanism underlies the difference in hyponatremia symptomatology and outcome.