Abstract: Objective o investigate the influencing factors for major adverse cardiovascular events (MACE) in patients undergoing maintenance hemodialysis (MHD) and to analyze the predictive value of combined detection of serum asymmetric dimethylarginine (ADMA), nuclear factor erythroid 2-related factor 2 (NRF2), and gasdermin D (GSDMD) for the occurrence of MACE.  Methods  MHD patients admitted to Shaanxi Provincial Hospital of Traditional Chinese Medicine from February 2019 to February 2024 were selected as the case group and divided into a MACE group and a non-MACE group based on whether MACE occurred. Healthy volunteers undergoing physical examinations during the same period were selected as the control group. Serum levels of ADMA, NRF2, and GSDMD were measured by ELISA. The predictive value of combined serum ADMA, NRF2, and GSDMD for MACE was evaluated using ROC curve analysis. Multivariate logistic regression was used to analyze related risk factors affecting MACE occurrence.  Results  The case group included 238 patients, with 81 in the MACE group and 157 in the non-MACE group; the control group included 119 individuals. Compared with the control group, serum levels of ADMA, NRF2, and GSDMD were elevated in the case group (t=44.339, 41.996, 42.793, all P＜0.001). Compared with the non-MACE group, the MACE group showed increased serum levels of ADMA (t=8.241, P＜0.001), NRF2 (t=8.997, P＜0.001), GSDMD (t=8.323, P＜0.001), as well as longer dialysis vintage (t=7.209, P＜0.001), and higher levels of hypersensitive C-reactive protein (hs-CRP) (t=5.661, P＜0.001), serum phosphorus (t=4.896, P＜0.001), serum calcium (t=12.623, P＜0.001), and intact parathyroid hormone (iPTH) (t=4.454, P＜0.001). The area under the curve (AUC) for the combined prediction of MACE in MHD patients by serum ADMA, NRF2, and GSDMD was 0.934, which was higher than that of individual markers (Z=4.631, 3.553, 3.691, all P＜0.001). Serum calcium (OR=2.661, 95% CI: 1.301～5.442, P=0.007), iPTH (OR=3.136, 95% CI: 1.477～6.656, P=0.003), ADMA (OR=3.628, 95% CI: 1.802～7.304, P＜0.001), NRF2 (OR=4.129, 95% CI: 1.882～9.061, P＜0.001), and GSDMD (OR=3.284, 95% CI: 1.901～5.67, P＜0.001) were identified as risk factors for MACE in MHD patients.  Conclusion  ADMA, NRF2, GSDMD, dialysis vintage, serum calcium, and iPTH are all risk factors for MACE in MHD patients. Combined detection of serum ADMA, NRF2, and GSDMD has high predictive value for the occurrence of MACE in MHD patients.

Key words: Maintenance hemodialysis, Major adverse cardiovascular events, Asymmetric dimethylarginine, Nuclear factor erythroid 2 related factor 2, Gasdermin D