Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands.
Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Eur J Vasc Endovasc Surg. 2023 Feb;65(2):282-290. doi: 10.1016/j.ejvs.2022.10.045. Epub 2022 Nov 2.
Plasma extracellular vesicles (EV) are an emerging source of biomarkers for diagnosis and prognosis of cardiovascular disease (CVD). Risk stratification for common adverse events such as major adverse limb events (MALE) and major adverse cardiovascular events (MACE) by an EV blood sample could improve healthcare management by individualising drug therapy or improving informed decision making regarding revascularisations in patients with peripheral artery disease (PAD). As such, this study investigated the associations between plasma EV proteins and prospectively registered MALE and MACE in consecutive patients undergoing femoral endarterectomy.
Using the Athero-Express biobank study, four EV proteins (Cystatin C, CD14, Serpin C1, and Serpin G1) were measured in the high density lipoprotein subfraction isolated from plasma of 317 PAD patients undergoing arterial revascularisation. Multivariable Cox proportional hazard regression was used to investigate the association between plasma EV protein levels and MACE and MALE in the three year post-operative period.
Most patients were treated for claudication (Fontaine II, 52.8%), although rest pain (Fontaine III, 30.1%) and ischaemic wounds (Fontaine IV, 17.1%) were common in this cohort. Within three years 51 patients died, amongst whom 25 deaths were due to CVD, 39 patients experienced a MACE, and 125 patients experienced a MALE. Multivariable regression models, based on statistically proven covariables and literature, showed a significant association of Serpin G1 (HR 1.49; 95% CI 1.08 - 2.06; p = .016) and CD14 (HR 1.40; 1.03 - 1.90; p = .029) with MACE, and of Serpin G1 (HR 1.29; 1.07 - 1.57; p = .009) with MALE.
Serpin G1 and CD14 plasma EV protein levels are associated with future MACE and MALE in patients with severe PAD.
血浆细胞外囊泡（EV）是诊断和预测心血管疾病（CVD）的新兴生物标志物来源。通过 EV 血样对常见不良事件（如主要不良肢体事件[MALE]和主要不良心血管事件[MACE]）进行风险分层，可通过个体化药物治疗或改善对周围动脉疾病（PAD）患者血运重建的知情决策，改善医疗保健管理。因此，本研究调查了连续接受股动脉内膜切除术的患者血浆 EV 蛋白与前瞻性登记的 MALE 和 MACE 之间的相关性。
使用 Athero-Express 生物库研究，对 317 名接受动脉血运重建的 PAD 患者的高密度脂蛋白亚组分中四种 EV 蛋白（胱抑素 C、CD14、丝氨酸蛋白酶抑制剂 C1 和丝氨酸蛋白酶抑制剂 G1）进行了测量。使用多变量 Cox 比例风险回归分析，研究术后三年内血浆 EV 蛋白水平与 MACE 和 MALE 的关系。
大多数患者因跛行（Fontaine II，52.8%）接受治疗，尽管该队列中常见静息痛（Fontaine III，30.1%）和缺血性溃疡（Fontaine IV，17.1%）。三年内有 51 名患者死亡，其中 25 例死亡归因于 CVD，39 例发生 MACE，125 例发生 MALE。基于统计学上证明的协变量和文献的多变量回归模型显示，丝氨酸蛋白酶抑制剂 G1（HR 1.49；95%CI 1.08-2.06；p=0.016）和 CD14（HR 1.40；1.03-1.90；p=0.029）与 MACE 显著相关，丝氨酸蛋白酶抑制剂 G1（HR 1.29；1.07-1.57；p=0.009）与 MALE 显著相关。
严重 PAD 患者的血浆 EV 蛋白丝氨酸蛋白酶抑制剂 G1 和 CD14 水平与未来的 MACE 和 MALE 相关。
