Association of growth differentiation factor 15 with other key biomarkers, functional parameters and mortality in community-dwelling older adults

Abstract

Background: Growth differentiation factor 15 (GDF-15) has been associated with many adverse age-related outcomes and other age-related disorders. The aim of the study was to investigate if baseline levels of GDF-15 are associated with total mortality in community living, older adults during eight years of follow-up after simultaneous consideration of key biomarkers and functional parameters.

Methods: prospective cohort study including 1,470 community-dwelling older adults aged 65 years or older. GDF-15 was measured by ElectroChemi-Lumisnescence Immunoassays (Roche, Mannheim, Germany). We used Cox-proportional hazards regression to estimate the association of GDF-15 levels with 8-year all-cause mortality.

Results: GDF-15 levels were independently of age and sex strongly associated with many biomarkers such as CRP, IL-6, NT-proBNP, hs-troponines as well as with lipids, metabolic and endocrine markers and kidney function (all P-values < 0.001). GDF-15 showed also a statistically significant correlation to gait speed, hand grip strength and walking duration. In addition, we found a consistent association between levels of GDF-15 and risk of subsequent all-cause mortality which persisted after additional adjustment for key markers of inflammation, cardiac function and damage, and physical function. The hazard ratio (HR) per unit increase of log-transformed GDF-15 was 1.72 (95% CI 1.35; 2.18).

Conclusions: GDF-15 levels were not only strongly associated with many functional parameters and key biomarkers independently of age and sex, but also with 8-year all-cause mortality even after adjusting for gait speed, NT-proBNP and hs-TnT.

Keywords: biomarkers; cohort study; growth differentiation factor 15; mortality; older people.