E-选择素和 sICAM-1，内皮功能的生物标志物，可预测静脉血栓栓塞复发。

E-selectin and sICAM-1, biomarkers of endothelial function, predict recurrence of venous thromboembolism.

机构信息

The Medical University of Warsaw, Department of Internal Medicine & Cardiology, Poland.

出版信息

Thromb Res. 2017 Sep;157:173-180. doi: 10.1016/j.thromres.2017.07.027. Epub 2017 Jul 26.

DOI:10.1016/j.thromres.2017.07.027

PMID:28780342

Abstract

BACKGROUND

Risk factors for atherosclerosis and venous thromboembolism (VTE) overlap and are mostly associated with endothelial dysfunction (ED). We hypothesized that ED is present in patients after the first episode of acute pulmonary embolism (APE) and predicts the risk of VTE recurrence.

DESIGN AND METHODS

Patients, at least 6months after the first episode of symptomatic, confirmed APE were included in this case-control study. The exclusion criteria were risk factors for cardiovascular diseases and other conditions associated with endothelial dysfunction. Eighty two patients (aged 38±11years; 44 M; 38 F) were enrolled in the study, 39 after provoked APE, 43 after unprovoked APE, and 30 controls (C) (aged 38±12years; 15 M, 15 F). In order to evaluate the endothelial function in patients with a history of APE flow-mediated dilation (FMD) of the brachial artery and biomarkers of endothelial dysfunction (sVCAM-1, sICAM-1, ADMA, E-selectin) were measured. Subsequently all patients were followed up in an outpatient clinic for VTE recurrence.

RESULTS

FMD was more often impaired in APE patients than in controls (5.3% (0.8-20.3) vs. 13.8% (4.1-24.3); p<0.0001). Biomarker levels differed between APE and C groups: sVCAM-1 (631ng/ml (105-2382) vs. 495ng/ml (348-934); p=0.04) and sICAM-1 (679ng/ml (279-1006) vs. 600ng/ml (394-766); p=0.002). There were 19 recurrences of VTE during the at least 12-month follow-up (15 with history of unprovoked-APE and 4 after provoked-APE). E-selectin ≥39ng/ml and sICAM-1≤655ng/ml indicated the group without recurrence of VTE. In a group of 43 unprovoked APE patients both E-selectin<39ng/ml and sICAM-1>655ng/ml were found in 17 subjects. Eleven of them (65%) were diagnosed with recurrent VTE.

CONCLUSIONS

Endothelial function is significantly impaired in patients after an episode of APE as indicated by FMD assessment and biomarker levels. Low concentrations of E-selectin and high levels of sICAM-1 are associated with a high risk of recurrent thromboembolism.

摘要

背景

动脉粥样硬化和静脉血栓栓塞症（VTE）的风险因素重叠，并且主要与内皮功能障碍（ED）有关。我们假设 ED 存在于首次急性肺栓塞（APE）发作后的患者中，并预测 VTE 复发的风险。

设计和方法

本病例对照研究纳入了至少在首次有症状、确诊的 APE 发作后 6 个月的患者。排除标准为心血管疾病的风险因素和其他与内皮功能障碍相关的疾病。82 名患者（年龄 38±11 岁；44 名男性；38 名女性）纳入研究，39 名因诱因引起的 APE，43 名无诱因引起的 APE，30 名对照组（C）（年龄 38±12 岁；15 名男性，15 名女性）。为了评估 APE 病史患者的内皮功能，测量了肱动脉血流介导的扩张（FMD）和内皮功能障碍的生物标志物（sVCAM-1、sICAM-1、ADMA、E-选择素）。随后，所有患者在门诊接受 VTE 复发的随访。

结果

APE 患者的 FMD 较对照组更常受损（5.3%（0.8-20.3）比 13.8%（4.1-24.3）；p<0.0001）。APE 组与 C 组的生物标志物水平不同：sVCAM-1（631ng/ml（105-2382）比 495ng/ml（348-934）；p=0.04）和 sICAM-1（679ng/ml（279-1006）比 600ng/ml（394-766）；p=0.002）。在至少 12 个月的随访期间，有 19 例 VTE 复发（15 例有非诱因性 APE 病史，4 例有诱因性 APE 病史）。E-选择素≥39ng/ml 和 sICAM-1≤655ng/ml 提示 VTE 无复发。在 43 例非诱因性 APE 患者中，有 17 例患者同时出现 E-选择素<39ng/ml 和 sICAM-1>655ng/ml。其中 11 例（65%）被诊断为 VTE 复发。