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

Abstract

Background: Receptor-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.

Methods: Plasma 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.

Results: Plasma 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).

Conclusions: Plasma 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.

Keywords: Diagnosis; Heart failure; Necroptosis; Prognosis; Receptor-interacting protein kinase-3 (RIP3); Risk factor.