Combined Effects of Biomarkers in NLRP3 Inflammasome Axis and Cardiovascular Outcomes in Multivessels Disease.
Inflammation plays a crucial role in adverse outcomes of coronary artery disease. NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activates 2 classical pathways: interleukin-1β (IL-1β)/IL-6/high-sensitivity C-reactive protein (hsCRP) and IL-18/IL-6/hsCRP. However, the predictive value of pathway-related biomarkers, particularly their combinations, remains to be systematically evaluated.
The authors aimed to explore the predictive value of individual and combined biomarkers from 2 pathways for long-term cardiovascular risk in patients with multivessel disease (MVD).
From a prospective, multicenter cohort, 1,058 consecutive patients with MVD were enrolled. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE-4P), a composite of all-cause death, myocardial infarction, revascularization, and stroke.
During a median 2-year follow-up (IQR: 2.0-2.1 years), 130/1,058 (12.3%) MACCE-4P occurred. After multivariable adjustment, higher levels of IL-1β (HR: 1.63; 95% CI: 1.15-2.32), IL-6 (1.72, 1.20-2.46), and hsCRP (1.59, 1.09-2.30) were associated with increased MACCE-4P risk, whereas IL-18 was not. For combined analysis, any 2-biomarker combination from either the IL-1β/IL-6/hsCRP or IL-18/IL-6/hsCRP pathway significantly predicted higher MACCE-4P risk (HR range: 1.84-2.19), with further risk elevation observed for the 3-biomarker combinations (HR: 3.09; 95% CI: 1.80-5.31 for IL-1β pathway; HR: 2.26; 95% CI: 1.24-4.14 for IL-18 pathway). The 4-biomarker combination (IL-1β+IL-6+IL-18+hsCRP) also predicted significantly higher MACCE-4P risk (HR: 2.64; 95% CI: 1.36-5.14). Notably, 3-/4-combined biomarkers demonstrated significant incremental predictive value over single biomarkers.
In patients with MVD, combined assessment of NLRP3-associated inflammatory biomarkers offers significant incremental predictive value beyond individual biomarkers. These findings highlight the importance of integrating multiple inflammatory biomarkers to better identify patients with residual inflammatory risk.
The authors aimed to explore the predictive value of individual and combined biomarkers from 2 pathways for long-term cardiovascular risk in patients with multivessel disease (MVD).
From a prospective, multicenter cohort, 1,058 consecutive patients with MVD were enrolled. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE-4P), a composite of all-cause death, myocardial infarction, revascularization, and stroke.
During a median 2-year follow-up (IQR: 2.0-2.1 years), 130/1,058 (12.3%) MACCE-4P occurred. After multivariable adjustment, higher levels of IL-1β (HR: 1.63; 95% CI: 1.15-2.32), IL-6 (1.72, 1.20-2.46), and hsCRP (1.59, 1.09-2.30) were associated with increased MACCE-4P risk, whereas IL-18 was not. For combined analysis, any 2-biomarker combination from either the IL-1β/IL-6/hsCRP or IL-18/IL-6/hsCRP pathway significantly predicted higher MACCE-4P risk (HR range: 1.84-2.19), with further risk elevation observed for the 3-biomarker combinations (HR: 3.09; 95% CI: 1.80-5.31 for IL-1β pathway; HR: 2.26; 95% CI: 1.24-4.14 for IL-18 pathway). The 4-biomarker combination (IL-1β+IL-6+IL-18+hsCRP) also predicted significantly higher MACCE-4P risk (HR: 2.64; 95% CI: 1.36-5.14). Notably, 3-/4-combined biomarkers demonstrated significant incremental predictive value over single biomarkers.
In patients with MVD, combined assessment of NLRP3-associated inflammatory biomarkers offers significant incremental predictive value beyond individual biomarkers. These findings highlight the importance of integrating multiple inflammatory biomarkers to better identify patients with residual inflammatory risk.
Authors
Li Li, Wang Wang, Liu Liu, Zhang Zhang, Zhang Zhang, Wang Wang, Feng Feng, Wang Wang, Guo Guo, Tang Tang, Xu Xu, Song Song, Chen Chen, Xu Xu, Yao Yao, Liu Liu, Zhu Zhu, Zhong Zhong, Ou Ou, Liu Liu, Han Han, Yuan Yuan, Zhao Zhao
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