Tsimikas Sotirios, Kille Alexander, Kaier Klaus, Nührenberg Thomas, Franke Kilian, Valina Christian M, Yang Xiaohong, Leibundgut Gregor, Neumann Franz-Josef, Westermann Dirk, Hochholzer Willibald
Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California San Diego (S.T., X.Y.).
Department of Cardiology and Angiology II, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg, Germany. (A.K., T.N., K.F., C.M.V., F.-J.N., D.W., W.H.).
Arterioscler Thromb Vasc Biol. 2025 Aug 14. doi: 10.1161/ATVBAHA.125.322347.
OxPL-apoB (oxidized phospholipids [OxPL] on apo B), which include OxPL present on Lp(a) (lipoprotein [a]), are associated with higher cardiovascular risk. Experimental studies suggest that OxPL may influence platelet function.
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.
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]; =0.010) and Lp(a) (hazard ratio, 1.002 [95% CI, 1.000-1.005]; =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]; =0.009) and for Lp(a) 30 mg/dL (hazard ratio, 1.261 [95% CI, 1.012-1.570]; =0.038).
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.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00457236.
氧化型载脂蛋白B（OxPL-apoB，即载脂蛋白B上的氧化磷脂[OxPL]，包括存在于脂蛋白[a][Lp(a)]上的OxPL）与较高的心血管疾病风险相关。实验研究表明，OxPL可能影响血小板功能。
在EXCELSIOR试验（择期支架植入术中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）的2040例接受或未接受经皮冠状动脉介入治疗的冠状动脉造影患者中，这项观察性研究评估了OxPL-apoB与内在及氯吡格雷治疗后的血小板反应性以及长期心血管事件之间的关联。确定了OxPL-apoB与CD62P、CD41或PAC-1水平的表达以及内在及氯吡格雷治疗后的血小板对胶原蛋白和二磷酸腺苷（ADP）的反应性之间的关联。使用Cox回归模型评估了OxPL-apoB和Lp(a)与中位7年无心肌梗死生存期和全因死亡率之间的关系。
OxPL-apoB水平升高与冠状动脉阻塞的严重程度相关，以及既往心肌梗死、经皮冠状动脉介入治疗和冠状动脉搭桥手术的较高患病率相关。OxPL-apoB与内在或氯吡格雷治疗后的血小板反应性或血小板受体激活之间无显著关联。在单独的多变量模型中分别分析时，OxPL-apoB（风险比，1.022[95%置信区间，1.005 - 1.040]；P = 0.010）和Lp(a)（风险比，1.002[95%置信区间，1.000 - 1.005]；P = 0.032）均与较差的无心肌梗死生存期相关。然而，在共同分析的联合多变量模型中，OxPL-apoB和Lp(a)均无显著性。OxPL-apoB无心肌梗死生存期的最佳切点为8 nmol/L（风险比，1.391[95%置信区间，1.086 - 1.780]；P = 0.009），Lp(a)的最佳切点为30 mg/dL（风险比，1.261[95%置信区间，1.012 - 1.570]；P = 0.038）。
在接受或未接受经皮冠状动脉介入治疗的冠状动脉造影患者中，OxPL-apoB与胶原蛋白或ADP介导的内在及氯吡格雷治疗后的血小板反应性无关。OxPL-apoB和Lp(a)之间的关联表明，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。
