氧化磷脂对载脂蛋白B100的影响，血小板活化和反应性，以及长期心血管预后。

IF 7.4 1区医学 Q1 HEMATOLOGY

Arteriosclerosis, Thrombosis, and Vascular Biology Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI:10.1161/ATVBAHA.125.322347

Sotirios Tsimikas, Alexander Kille, Klaus Kaier, Thomas Nührenberg, Kilian Franke, Christian M Valina, Xiaohong Yang, Gregor Leibundgut, Franz-Josef Neumann, Dirk Westermann, Willibald Hochholzer

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引用次数: 0

摘要

背景：OxPL- apob（载脂蛋白B100上的氧化磷脂[OxPL]），包括脂蛋白（脂蛋白[a]）上的OxPL，与较高的心血管风险相关。实验研究表明，OxPL可能影响血小板功能。方法：本观察性研究评估了EXCELSIOR试验（择期支架植入期间氯吡格雷诱导的血小板抑制程度对临床事件发生率的影响）中2040例接受冠状动脉造影或不经皮冠状动脉介入治疗的患者中OxPL-apoB与内在和非氯吡格雷血小板反应性和长期心血管事件的关系。测定OxPL-apoB与CD62P、CD41或PAC-1水平的表达以及血小板对胶原和ADP的内在和非氯吡格雷反应性的关系。使用Cox回归模型评估OxPL-apoB和Lp(a)与中位7年无心肌梗死生存率和全因死亡率的关系。结果：OxPL-apoB水平升高与冠状动脉阻塞的严重程度、既往心肌梗死、经皮冠状动脉介入治疗和冠状动脉搭桥手术的发生率升高有关。OxPL-apoB与固有或非氯吡格雷血小板反应性或血小板受体活化之间没有显著关联。在单独的多变量模型中单独分析，OxPL-apoB(风险比，1.022 [95% CI, 1.005-1.040]；P=0.010)和Lp(a)(风险比1.002 [95% CI, 1.000-1.005]；P=0.032)与较差的无心肌梗死生存相关。然而，在联合多变量模型中，OxPL-apoB和Lp(a)均不显著。OxPL-apoB无心肌梗死生存的最佳切割点为8 nmol/L(风险比，1.391 [95% CI, 1.086-1.780]；P=0.009), Lp(a)为30 mg/dL(风险比，1.261 [95% CI, 1.012-1.570]；P = 0.038)。结论：在接受冠状动脉造影或不经皮冠状动脉介入治疗的患者中，OxPL-apoB与胶原或ADP介导的内在和非氯吡格雷血小板反应性无关。OxPL-载脂蛋白ob与Lp(a)的关联表明，OxPL在Lp(a)上的积累可能是长期心血管结局的关键决定因素。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT00457236。

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Oxidized Phospholipids on ApoB-100, Platelet Activation and Reactivity, and Long-Term Cardiovascular Outcomes.

Background: OxPL-apoB (oxidized phospholipids [OxPL] on apoB-100), which include OxPL present on Lp(a) (lipoprotein[a]), are associated with higher cardiovascular risk. Experimental studies suggest that OxPL may influence platelet function.

Methods: This observational study assessed the association of OxPL-apoB with intrinsic and on‑clopidogrel platelet reactivity and long-term cardiovascular events in patients undergoing coronary angiography with or without percutaneous coronary intervention in 2040 patients in the EXCELSIOR trial (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate). The association of OxPL-apoB to expression of CD62P, CD41, or PAC-1 levels and intrinsic and on-clopidogrel platelet reactivity to collagen and ADP was determined. The relationship of OxPL-apoB and Lp(a) to myocardial infarction-free survival and all-cause mortality at a median of 7 years was assessed using Cox regression models.

Results: Elevated levels of OxPL-apoB were associated with the severity of coronary obstruction, and higher prevalence of prior myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft surgery. No significant associations were present between OxPL-apoB and intrinsic or on-clopidogrel platelet reactivity or activation of platelet receptors. Analyzed individually in separate multivariable models, both OxPL-apoB (hazard ratio, 1.022 [95% CI, 1.005-1.040]; P=0.010) and Lp(a) (hazard ratio, 1.002 [95% CI, 1.000-1.005]; P=0.032) were associated with worse myocardial infarction-free survival. However, in a joint multivariable model analyzed together, neither OxPL-apoB nor Lp(a) was significant. The optimal cut point for myocardial infarction-free survival for OxPL-apoB was 8 nmol/L (hazard ratio, 1.391 [95% CI, 1.086-1.780]; P=0.009) and for Lp(a) 30 mg/dL (hazard ratio, 1.261 [95% CI, 1.012-1.570]; P=0.038).

Conclusions: In patients undergoing coronary angiography with or without percutaneous coronary intervention, OxPL-apoB was not associated with intrinsic and on-clopidogrel platelet reactivity mediated by collagen or ADP. The association of OxPL-apoB and Lp(a) suggests that the accumulation of OxPL on Lp(a) may be a key determinant of long-term cardiovascular outcomes.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00457236.

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来源期刊

Arteriosclerosis, Thrombosis, and Vascular Biology 医学-外周血管病

CiteScore

15.60

自引率

2.30%

发文量

337

审稿时长

2-4 weeks

期刊介绍： The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.