High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms

J Vasc Surg. 2020 Jun;71(6):1921-1929. doi: 10.1016/j.jvs.2019.08.253. Epub 2019 Nov 26.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: High levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.

Keywords: Abdominal aorta aneurysms; Extracellular matrix; Growth rate; MFAP4; Surgical repair.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Aneurysm, Abdominal / blood*
  • Aortic Aneurysm, Abdominal / diagnostic imaging
  • Aortic Aneurysm, Abdominal / surgery*
  • Biomarkers / blood
  • Carrier Proteins / blood*
  • Denmark
  • Disease Progression
  • Extracellular Matrix Proteins / blood*
  • Glycoproteins / blood*
  • Humans
  • Male
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MFAP4 protein, human