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载脂蛋白酶 1(PON1)和髓过氧化物酶(MPO)作为两种与高密度脂蛋白相关的重要酶在冠心病中的联合效用:哪一种具有更强的预测作用?

The combined utility of myeloperoxidase (MPO) and paraoxonase 1 (PON1) as two important HDL-associated enzymes in coronary artery disease: Which has a stronger predictive role?

机构信息

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Atherosclerosis. 2019 Jan;280:7-13. doi: 10.1016/j.atherosclerosis.2018.11.004. Epub 2018 Nov 8.

Abstract

BACKGROUND AND AIMS

Serum paraoxonase 1 (PON1) and myeloperoxidase (MPO) are HDL-associated enzymes that contribute significantly to the formation of dysfunctional HDL. The present study thus seeks to comparatively analyze the predictive role of PON1, MPO and the MPO/PON1 ratio and to also evaluate which one has a stronger predictive role in their combined utility as an MPO/PON1 ratio in coronary artery disease (CAD).

METHODS

PON1 activity and MPO concentrations were determined in patients with established CAD and those without significant CAD. Receiver operating characteristic (ROC) curves were drawn by plotting true positivity versus false positivity.

RESULTS

The ROC curve analyses showed that PON1 (AUC = 61%, p = 0.003) and MPO/PON1 (AUC = 60%, p = 0.01) have a better diagnostic performance than MPO (AUC = 50%, p = 0.42) in detecting patients with CAD. PON1 and MPO/PON1 were found to have a significantly stronger discriminatory power for the age range ≥52 and < 60 years (AUC = 69%, p = 0.008 for PON1; AUC = 66%, p = 0.022 for MPO/PON1). The multivariate analysis revealed PON1 as an independent variable that was significantly associated with the multi-vessel disease [odds ratio (OR) = 0.98; p = 0.017]. At the cutoff point of 30 μmol/mL/min for PON1 and 1.85 for MPO/PON1, specificities were 97% and 73% and sensitivities 30% and 54% for discriminating patients with single-vessel disease from non-CAD subjects.

CONCLUSIONS

The diagnostic performance of PON1 alone was comparable to that of the MPO/PON1 ratio for CAD risk assessment; however, MPO may increase the true positive rate. A larger number of blocked vessels seems to be associated with an increased predictive power for both PON1 and MPO/PON1. Recent data support the fact that PON1 and MPO may potentially be appropriate therapeutic targets for preventing CAD.

摘要

背景和目的

血清对氧磷酶 1(PON1)和髓过氧化物酶(MPO)是与高密度脂蛋白(HDL)相关的酶,它们对形成功能失调的 HDL 有重要贡献。因此,本研究旨在比较分析 PON1、MPO 和 MPO/PON1 比值的预测作用,并评估在联合使用 MPO/PON1 比值作为冠心病(CAD)的预测因子时,哪一个具有更强的预测作用。

方法

测定了确诊 CAD 患者和无明显 CAD 患者的 PON1 活性和 MPO 浓度。通过绘制真阳性与假阳性率绘制受试者工作特征(ROC)曲线。

结果

ROC 曲线分析表明,与 MPO(AUC=50%,p=0.42)相比,PON1(AUC=61%,p=0.003)和 MPO/PON1(AUC=60%,p=0.01)在检测 CAD 患者方面具有更好的诊断性能。PON1 和 MPO/PON1 对年龄范围≥52 岁和<60 岁的患者具有更强的区分能力(PON1 的 AUC=69%,p=0.008;MPO/PON1 的 AUC=66%,p=0.022)。多变量分析显示 PON1 是与多血管疾病显著相关的独立变量[比值比(OR)=0.98;p=0.017]。当 PON1 的截断值为 30μmol/ml/min,MPO/PON1 的截断值为 1.85 时,用于区分单支血管病变患者和非 CAD 患者的特异性分别为 97%和 73%,敏感性分别为 30%和 54%。

结论

PON1 单独用于 CAD 风险评估的诊断性能与 MPO/PON1 比值相当,但 MPO 可能会提高真阳性率。更多的阻塞血管似乎与 PON1 和 MPO/PON1 两者的预测能力增加相关。最近的数据支持 PON1 和 MPO 可能是预防 CAD 的潜在合适治疗靶点这一事实。

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