Malnutrition and Muscle Loss Mediate the Association Between NT-proBNP and Mortality in Hospitalized Older Adults

Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker of cardiac stress, predicts mortality in heart failure. Its association with outcomes in older hospitalized patients without overt heart failure, and potential mediation by malnutrition and muscle loss, remains unclear. The purpose of this study was to assess the association between NT-proBNP and mortality in hospitalized oldest-old adults (≥80 years) and to explore the mediating role of malnutrition and muscle loss. This prospective cohort study was conducted among 360 hospitalized patients ≥ 80 years of age (median age 87 years, 24.4% women) in the Department of Geriatrics (Shanghai, China), between August 2017 and January 2018. The Geriatric Nutritional Risk Index (GNRI) and Mini Nutritional Assessment Short Form (MNA-SF) were used for nutritional assessment, while calf circumference was used as a measure of muscle mass. A Cox proportional hazard model was used to assess the relationship between NT-proBNP levels and mortality. Mediation analysis was used to explore the mediating effects of malnutrition and muscle loss. The median follow-up was 4.1 years with 159 (44.1%) deaths. Mortality risk increased by 32% per 2-fold increase in NT-proBNP levels (full adjusted hazard ratio: 1.32 [95% Confidence Interval (CI), 1.20-1.46]). A mediation analysis showed that a lower GNRI score and decreased calf circumference partially mediated the effects of high NT-proBNP and mortality risk, with an estimated relative effect size of 28.9%, while MNA-SF and calf circumference mediated with an estimated relative effect size of 25.3%. NT-proBNP levels were associated with increased mortality in hospitalized older patients. Moreover, the detrimental effects of NT-proBNP on survival were partly mediated by malnutrition and muscle loss. Consequently, preventive and nutritional strategies should be required for these patients.