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Thromb Haemost 2018; 118(04): 791-797
DOI: 10.1055/s-0038-1636543
Atherosclerosis and Ischaemic Disease
Schattauer GmbH Stuttgart

Angiopoietin-2 and Survival in Peripheral Artery Disease Patients

Clemens Höbaus
1   Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Gerfried Pesau
1   Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Carsten Thilo Herz
1   Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
2   Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
,
Thomas Wrba
3   IT4Science, IT-Systems and Communications, Medical University of Vienna, Vienna, Austria
,
Renate Koppensteiner
1   Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Gerit-Holger Schernthaner
1   Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
› Author Affiliations Funding Funding was provided by Medical University Vienna, Vienna, Austria.
Further Information

Publication History

18 October 2017

15 January 2018

Publication Date:
04 April 2018 (online)

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Abstract

Survival of peripheral arterial disease (PAD) patients increased over the last decade due to increased use of secondary preventive medication and rapid revascularization of PAD patients. Angiogenetic markers such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and its receptor Tie-2 might be useful markers to assess the residual risk for mortality in PAD patients. The aim of this study was to evaluate angiogenetic markers for the prediction of mortality in a PAD cohort. For this purpose, 366 patients (mean age: 69 ± 10 years) with PAD Fontaine stage I or II were included and followed up over a 5-year study period. Serum Ang-2, Tie-2 and VEGF levels were measured by bead-based multiplex assay. All-cause mortality and major cardiovascular events (MACE) including all-cause death, non-fatal stroke and non-fatal myocardial infarction were analysed by Kaplan–Meier and Cox regression analyses after 5 years. Ang-2 was associated with Tie-2 (R = 0.151, p = 0.006) and VEGF levels (R = 0.160, p = 0.002). However, only Ang-2 was linked to all all-cause mortality in PAD patients (hazard ratio [HR]: 1.55 [1.23–2.15], p = 0.008) even after adjustment for age and gender, haemoglobin A1c, low-density lipoprotein cholesterol, systolic blood pressure and glomerular filtration rate (HR: 1.44 [1.03–2.00], p = 0.032). Furthermore, an association of Ang-2 and MACE in PAD patients (HR: 1.36 (1.03–1.78), p = 0.028) was found. This result implies that Ang-2 might be used as an additional marker to stratify PAD patients to predict poor mid-term life expectancy.

Keywords

angiopoietin-2 - Tie-2 - vascular endothelial growth factor - mortality - peripheral arterial disease - atherosclerosis

Authors' Contributions

C.H. performed the literature search; designed the study; performed the Ang-2, Tie-2 and VEGF measurements; conducted the statistical analyses and interpretation of the results; and drafted the manuscript. G.P. contributed to the data collection of the VMC cohort and measurement of Ang-2, Tie-2 and VEGF. C.T.H. revised the statistical analyses, performed interpretation of the results and contributed to the drafting of the manuscript. T.W. contributed to the data collection, data coordination and data management. R.K. participated in the interpretation of the results and revised the manuscript. G.H.S. designed the VMC study cohort, directed and performed the statistical analyses, interpretation of the results and revised the manuscript. All authors read and approved the final manuscript.