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

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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.

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