Predictive Value of NLRP3 Inflammasome Activation for Unstable Plaques and Major Adverse Cardiovascular Events in Coronary Heart Disease

Yaping Liu,1 Xiangqian Guo,1 Jiping Pan,1 Jianjian Jin,2 Jing Li,2 Yanjun Hou,3 Mingzhen Wang,3 Jianhua Bai,3 Yan Fan2 1The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China; 2Department of Cardiology, Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China; 3Department of Cardiology, Dongxiang County Hospital, Linxia, 731400, People’s Republic of ChinaCorrespondence: Yan Fan, Email 441429048@qq.comBackground: The role of Nod-like receptor protein 3 (NLRP3) inflammasome activation in unstable plaques remains incompletely elucidated. This study aimed to investigate whether the NLRP3 inflammasome and its downstream cytokine IL-1β serve as predictors of unstable plaques and subsequent major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD).Methods: The study enrolled 232 patients diagnosed with CHD at Gansu Provincial Hospital between May 2023 and June 2024. Based on standardized plaque vulnerability criteria assessed by intravascular ultrasound (IVUS) or optical coherence tomography (OCT), patients were divided into a stable plaque group (n=143) and an unstable plaque group (n=89). Serum concentrations of NLRP3 and IL-1β were measured using ELISA. During a median follow-up of 14 months (IQR, 7– 20), the primary composite endpoint was MACE, defined as recurrent myocardial infarction, rehospitalization due to heart failure, or all-cause death.Results: NLRP3 and IL-1β were identified as independent predictors of unstable plaques in CHD (OR=1.002 and 1.030, respectively), demonstrating high predictive value for plaque rupture and erosion (AUCs: 0.817 and 0.727 for rupture; 0.760 and 0.758 for erosion). Furthermore, elevated levels of these biomarkers were independently associated with an increased risk of MACE (HR=1.006 for NLRP3; HR=1.056 for IL-1β). Kaplan-Meier analysis confirmed that patients with high biomarker levels experienced a significantly higher incidence of MACE (log-rank P < 0.001). The high predictive accuracy of both biomarkers for MACE was further substantiated by AUC values of 0.874 (NLRP3) and 0.870 (IL-1β).Conclusion: NLRP3 inflammasome activation is a key predictor of unstable plaques (including rupture and erosion) and subsequent MACE in CHD patients, highlighting its strong promise as a clinical biomarker for refining risk stratification and guiding future therapies. Keywords: coronary heart disease, unstable plaques, NLRP3 inflammasome, IL-1β, major adverse cardiovascular events