Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort

Oppong, Richard;Orru, Valeria;Marongiu, Michele;Qian, Yong;Sidore, Carlo;Delitala, Alessandro;Orru, Marco;Mulas, Antonella;Piras, Maria Grazia;Morrell, Christopher H.;Lai, Sandra;Schlessinger, David;Gorospe, Myriam;Cucca, Francesco;Fiorillo, Edoardo;Ding, Jun;Lakatta, Edward G.;Scuteri, Angelo

2025-01-01

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Abstract

BACKGROUND: Growth differentiation factor 15 (GDF-15) levels are emerging as a candidate biomarker of aging. The present study aimed to: (1) characterize the association of GDF-15 with the continuum of arterial stiffening, assessed as carotid-femoral pulse wave velocity, as age increases; (2) determine the predictive role of serum GDF-15 levels on mortality; and (3) identify genetic determinants of serum GDF-15 levels. METHODS AND RESULTS: Serum levels of GDF-15 and established cardiovascular risk factors, including pulse wave velocity, were assessed in a large (4736 individual) Sardinian population. Serum levels of GDF-15, which can be reliably measured repeatedly over time, increase with age; are associated with a stiffer aorta; “mediate” a large proportion of the age-associated increase in arterial stiffness; pose risks because of their association with greater mortality; and are significantly associated with the variant rs11549407, which causes thalassemia major in homozygosity. CONCLUSIONS: Because of its consistent ability to predict functional and clinical outcomes, including all-cause mortality, we conclude that GDF-15 serum levels serve as a robust biomarker for the continuum from health to the emergence of clinical disease during aging and, subsequently, to the likelihood of mortality.