鉴定用于诊断和预测腹主动脉瘤的新型生物标志物。

Identification of novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.

机构信息

Center for Primary Health Care Research, Lund University, Sweden.

Department of Vascular Diseases, Skåne University Hospital, Sweden.

出版信息

Eur J Prev Cardiol. 2020 Jan;27(2):132-142. doi: 10.1177/2047487319873062. Epub 2019 Aug 29.

DOI:10.1177/2047487319873062

PMID:31466471

Abstract

AIMS

Abdominal aortic aneurysm is a life-threatening condition due to the risk of aneurysm growth and rupture. There are no approved diagnostic or prognostic biomarkers for abdominal aortic aneurysm. We aimed to identify diagnostic and prognostic biomarkers for abdominal aortic aneurysm and to investigate their relationship with abdominal aortic aneurysm diameter and growth.

METHODS

In this case-control study, patients were included from an abdominal aortic aneurysm screening study on men aged ≥65 years. Of 24,589 examined men, 415 had abdominal aortic aneurysm, out of whom 134 consented to participate in the present study. One hundred and thirty-six screened men with aortic diameter <30 mm, matched for comorbidities and time of sampling were included as non-abdominal aortic aneurysm patients. Ninety-one cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III panel.

RESULTS

After Bonferroni correction, plasma levels of 21 proteins associated with proteolysis, oxidative-stress, lipid metabolism, and inflammation were significantly increased, whereas levels of paraoxonase 3, associated with high-density lipoprotein metabolism, were decreased in abdominal aortic aneurysm patients. Combination of growth/differentiation factor 15 and cystatin B had the best ability to discriminate abdominal aortic aneurysm from non-abdominal aortic aneurysm (area under the curve, 0.76; sensitivity, 80% and specificity, 52%). Myeloperoxidase showed the best prognostic value (area under the curve, 0.71; sensitivity, 80% and specificity, 59%) and higher baseline levels of myeloperoxidase were significantly associated with faster abdominal aortic aneurysm growth compared with lower levels, independent of baseline diameter.

CONCLUSIONS

We have identified multiple proteins associated with abdominal aortic aneurysm diameter and growth with a potential to become novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.

摘要

目的

腹主动脉瘤是一种危及生命的疾病，因为其存在动脉瘤生长和破裂的风险。目前尚无批准用于诊断或预测腹主动脉瘤的生物标志物。本研究旨在确定腹主动脉瘤的诊断和预后生物标志物，并研究其与腹主动脉瘤直径和生长的关系。

方法

在这项病例对照研究中，纳入了一项针对年龄≥65 岁男性的腹主动脉瘤筛查研究中的患者。在 24589 名接受检查的男性中，有 415 名患有腹主动脉瘤，其中 134 名同意参加本研究。134 名腹主动脉瘤患者的腹主动脉直径<30mm，匹配了合并症和取样时间，作为非腹主动脉瘤患者。通过 Proseek 多重 CVD III 面板检测了血浆样本中的 91 种心血管特定蛋白。

结果

经 Bonferroni 校正后，与蛋白酶解、氧化应激、脂质代谢和炎症相关的 21 种蛋白的血浆水平显著升高，而与高密度脂蛋白代谢相关的对氧磷酶 3 水平降低。生长/分化因子 15 和胱抑素 B 的联合具有区分腹主动脉瘤和非腹主动脉瘤的最佳能力（曲线下面积为 0.76；敏感性为 80%，特异性为 52%）。髓过氧化物酶显示出最佳的预后价值（曲线下面积为 0.71；敏感性为 80%，特异性为 59%），较高的髓过氧化物酶基线水平与较低的水平相比，与更快的腹主动脉瘤生长显著相关，独立于基线直径。