Prognostic value of a disintegrin and metalloproteinase Domain-8 in heart failure

Abstract

Background: Heart failure (HF) is a severe disease threatening people's health. The aim of this study is to find a significant biomarker inducive to predicting the prognosis of HF. Methods: GSE135055 and GSE161472 datasets were reanalyzed for exploring key genes related to HF. This single-center, prospective, observational cohort study enrolled 298 patients with or without HF from the Cardiology Department of Zhongda Hospital. Levels of ADAM8 were measured using ELISA kits. Major adverse cardiovascular events (MACEs) were defined as the composite end points of the first occurrence of rehospitalization because of HF or cardiac-related death during one-year follow-up. Results: (1) Bioinformatics analysis showed that ADAM8 was a key gene in HF via mainly regulating the mechanisms of extracellular matrix (ECM) organization. (2) Levels of ADAM8 were significantly increased in the HF group, compared to the non-failing (NF) group (p < 0.001), especially in patients with HFrEF (p < 0.05), and HFmEF (p < 0.05). The prevalence of HF in the high ADAM8 group (≧472.916 pg/mL) was significantly higher than in the low ADAM8 group (<472.916 pg/mL) (41.95 % vs 30.54 %, p < 0.01). (3) Correlation analysis revealed that ADAM8 was negatively correlated to the left ventricular ejection fraction (LVEF) (r = −0.272, p < 0.001). ROC analysis showed that the AUC of ADAM8 in predicting HF and predicting the MACE were 0.701 (p < 0.0001) and 0.683 (p < 0.0001), respectively. (4) Logistic and Cox regression both indicated that high ADAM8 expression can predict adverse prognosis of HF. Conclusions: ADAM8 may be a risk factor for HF, especially in cases of HFrEF and HFmEF. High ADAM8 expression in plasma was related to the decreased heart function, and can predict the adverse prognosis of HF.

Keywords

• ADAM8
• Heart failure
• Prognosis
• MACEs
• Bioinformatics