Plasma concentration of receptor-interacting protein kinase-3 as a potential biomarker for diagnosis and prognosis in heart failure

Abstract

BackgroundReceptor-interacting serine-threonine kinase 3 (RIP3) is a key mediator of programmed necrosis (necroptosis), and is implicated in cardiac remodeling and heart failure (HF) triggered by ischemia-reperfusion or oxidative stress in animal study. However, its value in the diagnosis and prognosis of human HF remains unclear. MethodsPlasma RIP3 concentrations in 91 HF patients and 95 healthy volunteers were detected by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value of RIP3. Follow-up was conducted, and the composite endpoint was defined as all-cause mortality/readmission due to decompensated HF/worse New York Heart Association (NYHA) functional class. The relationship between RIP3 and patient outcome was examined. ResultsPlasma concentrations of RIP3 were significantly increased in patients with HF compared to controls (P < 0.001). ROC analysis supported plasma RIP3 as a good diagnostic marker for HF, with an optimal cutoff value of 357 pg/ml (AUC = 0.934, sensitivity = 0.846, specificity = 0.905). Kaplan-Meier survival analysis also supported increased plasma RIP3 as a predictor for a poor prognosis in HF (cutoff value = 622.2 pg/ml, P < 0.05). Additionally, binary logistic regression analysis revealed RIP3 to be an independent risk factor for all-cause mortality (OR = 11.844, P = 0.02), worse NYHA (OR = 9.013, P = 0.009) and a composite endpoint (OR = 5.065, P = 0.013). ConclusionsPlasma concentration of RIP3 is significantly elevated in HF and associated with the prognosis. Plasma RIP3 possibly constitutes a valuable diagnostic and prognostic biomarker for HF.