Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort
Richard Oppong, Valeria Orrù, Michele Marongiu, Yong Qian, Carlo Sidore, Alessandro Delitala, Marco Orrù, Antonella Mulas, Maria Grazia Piras, Christopher H. Morrell, Sandra Lai, David Schlessinger, Myriam Gorospe, Francesco Cucca, Edoardo Fiorillo, Jun Ding, Edward G. Lakatta, Angelo Scuteri
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.