Serum Levels of TNFAIP3 and NLRP3 as Novel Biomarkers for Major Adverse Cardiovascular Events in Patients with Chronic Heart Failure: A Cohort Study.

Purpose: Chronic heart failure (CHF) is a major public health issue with high morbidity and mortality, where inflammation plays a key role in its progression. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and NOD-like receptor protein 3 (NLRP3) regulate inflammatory responses, but their prognostic value in CHF remains unclear. This study aims to investigate the association between serum levels of TNFAIP3 and NLRP3 and the risk of major adverse cardiovascular events (MACEs) in patients with CHF. Patients and Methods: A cohort study was conducted involving 318 patients with CHF and 122 controls. Serum levels of TNFAIP3 and NLRP3 were measured using enzyme-linked immunosorbent assay method. Propensity score matching (PSM) was used to control for confounders. Multivariable logistic regression, restricted cubic spline, threshold effect, and receiver operating characteristic (ROC) analyses were employed to evaluate the associations between biomarker levels and MACEs over a 6-month follow-up. Results: After PSM, patients with CHF had significantly higher TNFAIP3 and NLRP3 levels than controls (both p < 0.001). Compared to CHF patients without MACEs, those with MACEs exhibited significantly lower levels of TNFAIP3 and higher levels of NLRP3. Multivariable analysis confirmed TNFAIP3 as an independent protective factor [odds ratio (OR)= 0.61, 95% confidence interval (CI): 0.40-0.93) and NLRP3 as an independent risk factor (OR = 1.24, 95% CI: 1.17-1.31) for MACEs. ROC analysis demonstrated NLRP3 (AUROC = 0.756) had better predictive ability than TNFAIP3 (AUROC = 0.611). Conclusion: TNFAIP3 and NLRP3 are significantly associated with the risk of MACEs in patients with CHF and NLRP3 demonstrates stronger predictive performance than TNFAIP3.