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血浆中性粒细胞明胶酶相关脂质运载蛋白水平与冠心病的存在和严重程度相关。

Plasma neutrophil gelatinase-associated lipocalin levels are associated with the presence and severity of coronary heart disease.

机构信息

The First Clinical College of Lanzhou University, Lanzhou, Gansu, China.

Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.

出版信息

PLoS One. 2019 Aug 6;14(8):e0220841. doi: 10.1371/journal.pone.0220841. eCollection 2019.

Abstract

OBJECTIVE

This study aimed to compare the levels of plasma neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL)-1β across different clinical presentations of coronary artery disease and to evaluate the relationship between those biomarkers and the severity of coronary artery lesions in patients without kidney disease.

METHODS

We examined 365 eligible patients who underwent coronary angiography. A total of 124 ST-segment elevation myocardial infarction (STEMI) patients, 117 stable angina pectoris (SAP) patients and 124 patients without atherosclerotic plaques were enrolled in the study. Plasma NGAL, MMP-9, hs-CRP, and IL-1β were measured in all patients using the enzyme-linked immunosorbent assay (ELISA) method. According to the SYNTAX score, the STEMI patients and SAP patients were divided into another set of 2 groups: a high score group (≥ 33, n = 29) and a low score group (<33, n = 212). The relationship between those biomarkers and the severity of coronary stenosis was examined by Spearman correlation analysis; the ability for NGAL to discriminate severe coronary stenosis was examined by receiver operating characteristic (ROC) curve; the influencing factors for the SYNTAX score were determined by logistic regression analysis.

RESULTS

Plasma NGAL, MMP-9, and hs-CRP levels in STEMI patients were higher than in the SAP patients and control subjects (P<0.05, respectively), and plasma NGAL and hs-CRP levels were significantly higher in the SAP patients than in control subjects (P<0.05, respectively), while plasma IL-1β was similar among the 3 groups (P>0.05, respectively). The SYNTAX score was positively related to NGAL (r = 0.363, P<0.001), MMP-9 (r = 0.377, P<0.001), and hs-CRP (r = 0.163, P<0.011); the SYNTAX score was not related to IL-1β (r = -0.043, P = 0.510). Plasma NGAL was positively related to MMP-9 (r = 0.601, P<0.001) and IL-1β (r = 0.159, P = 0.014). The area under the ROC curve for NGAL discriminating severe coronary stenosis was 0.838 (95% CI: 0.752-0.923, P<0.001), which was greater than that for MMP-9 [0.818, (95% CI: 0.724-0.912, P<0.001)], IL-1β [0.485, (95% CI: 0.369-0.601, P = 0.791)], and hs-CRP [0.607, (95% CI: 0.492-0.722, P = 0.061)]. Multivariate regression analysis showed that plasma NGAL levels were independently related to high SYNTAX scores [OR = 1.109, (95% CI: 1.104-1.114), P<0.001].

CONCLUSION

Plasma NGAL, MMP-9, and hs-CRP levels in STEMI patients were higher than those in the SAP patients and control subjects. NGAL had a better ability to discriminate severe coronary stenosis than MMP-9, IL-1β, and hs-CRP. NGAL may be a novel biomarker to aid in risk stratification in coronary heart disease patients.

摘要

目的

本研究旨在比较不同冠状动脉疾病临床表型患者的血浆中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、基质金属蛋白酶(MMP)-9、高敏 C 反应蛋白(hs-CRP)和白细胞介素(IL)-1β水平,并评估这些生物标志物与无肾病患者冠状动脉病变严重程度之间的关系。

方法

我们检查了 365 名接受冠状动脉造影的合格患者。共纳入 124 例 ST 段抬高型心肌梗死(STEMI)患者、117 例稳定型心绞痛(SAP)患者和 124 例无动脉粥样硬化斑块患者。采用酶联免疫吸附试验(ELISA)法检测所有患者的血浆 NGAL、MMP-9、hs-CRP 和 IL-1β。根据 SYNTAX 评分,将 STEMI 患者和 SAP 患者分为另一组:高分组(≥33,n=29)和低分组(<33,n=212)。通过 Spearman 相关分析检查这些生物标志物与冠状动脉狭窄严重程度之间的关系;通过接收者操作特征(ROC)曲线检查 NGAL 区分严重冠状动脉狭窄的能力;通过逻辑回归分析确定 SYNTAX 评分的影响因素。

结果

STEMI 患者的血浆 NGAL、MMP-9 和 hs-CRP 水平高于 SAP 患者和对照组(分别为 P<0.05),而 SAP 患者的血浆 NGAL 和 hs-CRP 水平明显高于对照组(分别为 P<0.05),而三组间的血浆 IL-1β水平无差异(分别为 P>0.05)。SYNTAX 评分与 NGAL(r=0.363,P<0.001)、MMP-9(r=0.377,P<0.001)和 hs-CRP(r=0.163,P<0.011)呈正相关;SYNTAX 评分与 IL-1β无相关性(r=-0.043,P=0.510)。血浆 NGAL 与 MMP-9(r=0.601,P<0.001)和 IL-1β(r=0.159,P=0.014)呈正相关。NGAL 区分严重冠状动脉狭窄的 ROC 曲线下面积为 0.838(95%CI:0.752-0.923,P<0.001),大于 MMP-9 [0.818,(95%CI:0.724-0.912,P<0.001)]、IL-1β [0.485,(95%CI:0.369-0.601,P=0.791)]和 hs-CRP [0.607,(95%CI:0.492-0.722,P=0.061)]。多变量回归分析显示,血浆 NGAL 水平与高 SYNTAX 评分独立相关[OR=1.109,(95%CI:1.104-1.114),P<0.001]。

结论

STEMI 患者的血浆 NGAL、MMP-9 和 hs-CRP 水平高于 SAP 患者和对照组。NGAL 区分严重冠状动脉狭窄的能力优于 MMP-9、IL-1β 和 hs-CRP。NGAL 可能是一种新型的冠心病患者危险分层的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e29b/6684288/0f33c88b4f75/pone.0220841.g001.jpg

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