Cardiovascular Research Unit, Viborg Hospital, Viborg, Denmark.
Cancer and Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
J Vasc Surg. 2020 Jun;71(6):1921-1929. doi: 10.1016/j.jvs.2019.08.253. Epub 2019 Nov 26.
Identifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA.
Plasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair.
A significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = -0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair.
High levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.
鉴定腹主动脉瘤(AAA)的生物标志物可能有助于 AAA 的预后,从而选择治疗方法。微纤维相关蛋白 4(MFAP4)是一种在主动脉中高度表达的细胞外基质蛋白。MFAP4 参与多种与组织重塑相关的疾病。我们旨在研究血浆 MFAP4(pMFAP4)作为 AAA 生物标志物的潜在作用。
在 Viborg 血管(VIVA)筛查试验中,获得了 504 名男性 AAA 患者和 188 名对照者的血浆样本和数据。通过 Alphalisa 测量 pMFAP4 水平。使用 Mann-Whitney U 检验评估不同暴露因素存在和不存在时 pMFAP4 水平的差异。通过 Spearman 相关分析研究 pMFAP4 与主动脉生长率之间的相关性。通过免疫组织化学和多元逻辑回归调整潜在混杂因素,评估 pMFAP4 与 AAA 之间的关系。多元线性回归评估 pMFAP4 与主动脉生长率之间的相关性。Cox 回归和竞争风险回归用于研究 pMFAP4 上三分位的 AAA 患者与随后手术修复风险之间的相关性。
Spearman 相关分析显示 pMFAP4 与主动脉生长率之间存在显著负相关(ρ=-0.14;P=0.0074)。然而,当应用多元线性回归时,这一发现并不显著。免疫组织化学显示 AAA 中 pMFAP4 水平降低。调整潜在混杂因素的竞争风险回归表明,pMFAP4 上三分位的患者随后手术修复的风险比为 0.51(P=0.001)。
高水平的 pMFAP4 与 AAA 接受手术修复的可能性降低有关。这一观察结果需要在独立队列中得到证实。