Heart Failure Related Fatigue and Serum Osmolality: An Exploratory Analysis of the National Health and Nutrition Examination Survey

Purpose

The purpose of this study was to explore the relationship of serum osmolality to HF-related fatigue, controlling for select physiologic covariates.

Background

Fatigue is a common symptom of heart failure (HF) associated with deleterious outcomes including increased morbidity and mortality. Underlying physiologic mechanisms of HF-related fatigue are not well understood. Hypervolemia and hypovolemia have been suggested as potential mechanisms of HF-related fatigue. Serum osmolality has been used as a physiologic measure to assess changes in volume status with therapeutic treatments to manage fluid imbalances. Low serum osmolality is associated with increased risk of mortality and hospital readmission in persons with HF. However, the relationship of serum osmolality and HF-related fatigue has not been well described.

Methods

We analyzed cross-sectional data from two waves of the National Health and Nutrition Examination Survey (2015-2016 and 2017-2018). Adults who self-reported having HF without co-morbid conditions known to contribute to fatigue were included in the study (unweighted n = 126). Data were weighted to provide US national estimates, and complex sample design used for analyses. Independent t tests and chi-square tests were used to explore differences between fatigued and nonfatigued adults with HF. Logistic regression analyses were used to calculate the odds of having fatigue. Bivariate logistic regression models were performed to assess the individual contributions of select physiologic covariates: age, sex, hemoglobin, body mass index (BMI) and presence of shortness of breath. Covariates with a significance of p≤.10 were included in the final model. Multivariate logistic regression was performed on the presence of fatigue as the outcome with physiologic predictors selected from the bivariate analysis: BMI and serum osmolality.

Results

Being female was associated with higher odds of experiencing fatigue when controlling for serum osmolality and body mass index (OR=4.91, p<.001, CI 2.200 – 10.954). Serum osmolality was lower in those that experienced fatigue compared to those without fatigue (t=-2.37, p=.032) Higher serum osmolality was associated with 7.6% lower odds of experiencing fatigue when controlling for sex and BMI (OR=.924, p=.014, CI .870 - .982).

Conclusion

Despite the deleterious outcomes associated with HF-related fatigue, physiologic mechanisms remain poorly understood. Serum osmolality may be associated with the experience of fatigue in persons with HF. Serum osmolality reflects the concentration of serum sodium, urea, and glucose. The differences in serum osmolality noted may be explained by dietary sodium, serum blood glucose, fluid restrictions or use of diuretics. Yet, serum osmolality is associated with mortality in persons with HF, suggesting changes in serum osmolality may inform disease severity and may influence the presentation of symptoms. Our findings also suggest HF-related fatigue may follow a sexually dimorphic pattern. Differences in symptom presentation may be related to physiologic differences. Women compared to men, have smaller ventricular mass, increased myocardial contractility, lower cellular turnover, lower blood pressures, less catecholamine-mediated vasoconstriction, and less total body water. These physiologic differences may contribute to fatigue presentation and severity of fatigue. Sex-based interventions may therefore be useful in managing the symptom.