CC BY-NC-ND 4.0 · Thromb Haemost 2019; 119(05): 807-820
DOI: 10.1055/s-0039-1679939
New Technologies, Diagnostic Tools and Drugs
Georg Thieme Verlag KG Stuttgart · New York

A Novel Diagnostic and Prognostic Score for Abdominal Aortic Aneurysms Based on D-Dimer and a Comprehensive Analysis of Myeloid Cell Parameters

Branislav Zagrapan
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Wolf Eilenberg
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Suriya Prausmueller
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Paimann Nawrozi
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Katharina Muench
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Sarah Hetzer
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Vanessa Elleder
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Renata Rajic
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Felix Juster
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Luca Martelanz
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Hubert Hayden
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Johannes Klopf
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Cansu Inan
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Peter Teubenbacher
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Markus P. Weigl
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Patrick Kirchweger
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Dietrich Beitzke
2  Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Bernd Jilma
3  Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Johann Wojta
4  Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Marc A. Bailey
5  Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
6  Leeds Vascular Institute, Leeds General Infirmary, Leeds, United Kingdom
,
D. Julian A. Scott
6  Leeds Vascular Institute, Leeds General Infirmary, Leeds, United Kingdom
5  Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
,
Ihor Huk
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
Christoph Neumayer
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
,
1  Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
› Author Affiliations
Funding This work was primarily supported by the Austrian Science Fund (SFB project F 5409-B21) as well as the Medical Scientific Fund of the Mayor of the City of Vienna (project 15012) and The Garfield Weston Foundation (for the Leeds Aneurysm Development Study). Marc Bailey is supported by the British Heart Foundation. The sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the article for publication.
Further Information

Publication History

27 October 2018

12 January 2019

Publication Date:
01 March 2019 (eFirst)

  

Abstract

The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors of myeloid cell activation and recruitment. To establish their marker potential, neutrophil and monocyte sub-sets were measured by flow cytometry in peripheral blood samples of 41 AAA patients and 38 healthy controls matched for age, sex, body mass index and smoking habit. Comparably, circulating factors reflecting neutrophil and monocyte activation and recruitment were assayed in plasma. Significantly elevated levels of CD16+ monocytes, activated neutrophils and newly released neutrophils were recorded for AAA patients compared with controls. In line, the monocyte chemoattractant C-C chemokine ligand 2 and myeloperoxidase were significantly increased in patients' plasma. The diagnostic value was highest for myeloperoxidase, a mediator which is released by activated neutrophils as well as CD16+ monocytes. Multivariable regression models using myeloid activation markers and routine laboratory parameters identified myeloperoxidase and D-dimer as strong independent correlates of AAA. These two biomarkers were combined to yield a diagnostic score which was subsequently challenged for confounders and confirmed in a validation cohort matched for cardiovascular disease. Importantly, the score was also found suited to predict rapid disease progression. In conclusion, D-dimer and myeloperoxidase represent two sensitive biomarkers of AAA which reflect distinct hallmarks (thrombus formation and inflammation) of the pathomechanism and, when combined, may serve as diagnostic and prognostic AAA score warranting further evaluation.

Supplementary Material