Xiaomin Hu1, Hanyu Li2, Xi Chen2, Honghong Liu2, Wei Zuo3, Yan Zhang4, Shuyang Zhang5. 1. Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China. 2. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China. 3. Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China. 4. Institute of Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, 100083 Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, 100083 Beijing, China. 5. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China. Electronic address: shuyangzhang103@nrdrs.org.
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.
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.