解析非靶病变的快速进展：PCI 后患者 PCSK9 抑制剂的风险因素和治疗潜力。

Unraveling the rapid progression of non-target lesions: risk factors and the therapeutic potential of PCSK9 inhibitors in post-PCI patients.

机构信息

Department of Cardiology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.

International Medical Department, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.

出版信息

BMC Cardiovasc Disord. 2024 Sep 18;24(1):499. doi: 10.1186/s12872-024-04186-2.

DOI:10.1186/s12872-024-04186-2

PMID:39294556

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11409538/

Abstract

BACKGROUND

Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms.

METHODS

This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1β, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI.

RESULTS

There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI).

CONCLUSIONS

LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque.

TRIAL REGISTRATION

ChiCTR2200058529; Date of registration: 2022-04-10.

摘要

背景

非靶病变（NTL）的快速进展导致 PCI 后 NTL 相关心脏事件的发生率很高，占复发性心脏事件的一半。识别危险因素并建立准确的 PCI 后 NTL 快速进展的临床预测模型非常重要。PCSK9 抑制剂可显著降低 LDL-c 水平，还具有抗炎作用，可能具有降低 PCI 后 NTL 快速进展的潜力。我们试图验证这一假设并探讨其潜在机制。

方法

本回顾性研究纳入了 1250 例首次接受 PCI 治疗且在 24 个月内因胸痛复发而行重复冠状动脉造影的患者。收集一般特征、实验室检查和炎症因子（IL-10、IL-6、IL-8、IL-1β、sIL-2R 和 TNF-α）。主要采用机器学习（LASSO 回归）来筛选 PCI 后 NTL 快速进展的重要特征风险因素，并构建预测模型。最后，采用中介分析探讨 PCSK9 抑制剂降低 PCI 后 NTL 快速进展的潜在机制。

结果

NTL 进展组的糖尿病、β受体阻滞剂和 PCSK9 抑制剂的应用较少，HbA1c、LDL-c、ApoB、TG、TC、尿酸、hs-CRP、TNF-α、IL-6、IL-8 和 sIL-2R 较高。LDL-c、hs-CRP、IL-8 和 sIL-2R 是 PCI 后 NTL 快速进展的特征风险因素，结合 LDL-c、hs-CRP、IL-8 和 sIL-2R 可构建预测 PCI 后 NTL 快速进展的最佳模型（AUC=0.632）。LDL-c 在 PCSK9 抑制剂降低 NTL 进展中具有明确且不完全的中介作用（95%CI，中介效应：51.56%），IL-8（90%CI）和 sIL-2R（90%CI）可能具有潜在的中介作用。

结论

LDL-c、hs-CRP、IL-8 和 sIL-2R 可能是 PCI 后 NTL 快速进展的关键特征风险因素，结合这些参数可能预测 NTL 快速进展。PCSK9 抑制剂的应用与 NTL 的快速进展呈负相关。除了显著降低 LDL-c 外，PCSK9 抑制剂还可能通过降低斑块局部炎症来降低 NTL 的快速进展。