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

Abstract

Growth differentiation factor 15 (GDF15) 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). We aimed to identify the determinants of GDF15 circulating levels in patients admitted for an acute myocardial infarction (AMI). In our prospective study, all consecutive patients admitted from June 2016 to February 2018 for type 1 AMI in the Coronary Care unit from the CHU Dijon Bourgogne were included. Congestive HF patients were excluded. 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. Among the 297 AMI patients, median age was at 68 (58–78) y, 28% were women, 25% had diabetes and 60% were hypertensive. GDF15 levels (median = 1,196 (800–2,139) ng/L) were strongly correlated with age ( r = 0.499, 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 without HF (274/297), patients with in-hospital HF (21/297), GDF15 was twice higher (figure). By Receiving Operating Curve analysis GDF15 was associated with HF (AUC (95%CI) = 0.81 (0.70–0.91), P < 0.001). Moreover, GDF15 levels were negatively correlated with Left Ventricular Ejection Fraction ( r = −0.268, P < 0.001). Multivariate logistic regression analysis showed that high GDF15 [OR: 5.67; 95% CI (1.48–21.64)] is as independent estimate of HF, beyond age and other confounding ( fig. 1 ). 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.