• atherosclerotic cardiovascular disease
• cardiovascular risk factors
• growth differentiation factor-15

Objective: To understand why the protective effect of GDF-15, demonstrated in the in vitro studies, does not clearly emerge from the clinical studies.
Methods: We have analyzed the data of a cross sectional study in outpatients selected to have a large variability in the extent of micro and macro vascular disease, who have been extensively evaluated in terms of both cardiovascular risk factors and micro and macro vascular end-organ damage.
Results: Plasma GDF-15 is raised at the presence of all the major risk factors for atherosclerotic cardiovascular disease, cardiac diseases, microvascular organ damage (neuropathy and nephropathy) and large arteries disease. Ageing, diabetes and the degree of metabolic control are the only statistically independent predictors of plasma GDF-15. GDF-15 does not modify the impact of risk factors on carotid atherosclerosis (IMT), it seems to have a direct negative effect on peripheral arteriopathy (PWV and ABPI) and no effect on myocardial function (NT-proBNP). It seems to have a negative impact on ACR, to be protective for cardiac autonomic neuropathy, while it is neutral on endothelial function.
Conclusions: These findings altogether confirm the role of GDF-15 as a marker of cardiovascular risk and end-organ damage, but do not support a major role for GDF-15 per se or in the modulation of the impact of risk factors on micro and macro CV complications.