P4550Growth differentiation factor 15 as an integrative biomarker of heart failure in patients with acute myocardial infarction

Abstract

Abstract Background Growth differentiation factor 15 (GDF15), a stress-responsive cytokine member of the transforming growth factor-β family, is an emerging biomarker in cardiovascular (CV) diseases. GDF15 is weakly expressed in normal condition but increased in pathological situations such as inflammation, oxidative stress, and left ventricular remodeling. Recent data suggest GDF15 as a marker in heart failure (HF). Purpose We aimed to identify the determinants of GDF15 circulating levels in patients admitted for an acute myocardial infarction (AMI). Methods In our prospective study, all consecutive patients admitted from June 2016 to February 2018 for type 1 AMI in the Coronary Care unit from our University Hospital were included. Chronic HF patients were excluded. In-hospital severe HF was defined as killip class>2. Blood samples were taken on admission and serum levels of GDF15 were measured using a commercially available ELISA kit. Results Among the 284 AMI patients, median age was at 67 (57–78) y, 27% were women, 23% had diabetes and 59% were hypertensive. GDF15 levels (median = 1,144 (775–1,891) ng/L were strongly correlated with age (r=0.493, p<0.001), and elevated with most CV risk factors (i.e. hypertension, diabetes), prior CAD, chronic kidney disease (p<0.001 for all) and in patients with CRP >3 mg/L (p<0.001). When compared with patients who didn't develop severe HF (274/284), patients experiencing HF (10/284), GDF15 was more than twice higher (figure). By Receiving Operating Curve analysis, GDF15 was associated with HF (AUC (95% CI) = 0.716 (0.52–0.91), p=0.021). Moreover, GDF15 levels were negatively correlated with Left Ventricular Ejection Fraction (LVEF) (r=−0.193, p=0.001). Multivariate logistic regression analysis showed that GDF15 >5,000 ng/L [OR: 8.43; 95% CI (1.57–45.32)] is as independent estimate of HF, beyond age and other confounding (i.e. admission systolic blood pressure, LVEF and Log N-terminal pro-Brain Natriuretic Peptide). GDF15 levels according to HF development Conclusions These preliminary results suggest that GDF15 could be an integrative biomarker of severe HF in patient with AMI. Further studies are needed to elucidate the underlying mechanisms linking the cytokine with the development of HF.