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
