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Published on: September 22, 2020
Biomarkers of Neutrophil Activation in Patients with Symptomatic Chronic Peripheral Artery Disease Predict Worse
Giacomo Buso1,2, Elisabetta Faggin3, Alessandro Bressan3
1Angiology Division, Heart and Vessel Department, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
Insights
Neutrophil activation markers like polymorphonuclear neutrophil elastase, NGAL, and MPO are linked to peripheral artery disease (PAD). These markers, particularly MPO, predict major adverse cardiovascular and limb events in PAD patients.
Area of Science:
- Cardiovascular Disease Research
- Immunology and Inflammation
- Vascular Biology
Background:
- Neutrophils are implicated in cardiovascular disease, but their role in peripheral artery disease (PAD) is understudied.
- Limited evidence exists on neutrophil activation biomarkers in PAD patients and their prognostic significance.
Purpose of the Study:
- To measure neutrophil activation biomarkers in symptomatic chronic PAD patients versus controls.
- To assess the association between these biomarkers and PAD severity.
- To evaluate the prognostic value of these biomarkers for adverse cardiovascular and limb events.
Main Methods:
- Circulating markers of neutrophil degranulation (PMN elastase, NGAL, MPO) and neutrophil extracellular traps (MPO-DNA complexes) were measured.
- Patients with PAD underwent vascular tests and were monitored for 6-month major adverse CV (MACE) and limb events (MALE).
- Statistical analyses included logistic and Cox regression, and ROC curve analysis for MPO.
Main Results:
- PMN-elastase, NGAL, and MPO were significantly associated with the presence of PAD after adjusting for risk factors.
- PMN-elastase and MPO predicted 6-month MACE and/or MALE.
- MPO showed prognostic performance (AUC 0.74) for predicting events.
- MPO-DNA complexes showed a weak inverse correlation with foot oxygenation (TcPO2).
Conclusions:
- Enhanced neutrophil activity in symptomatic PAD patients is associated with an increased risk of acute cardiovascular events.
- Biomarkers of neutrophil activation, particularly MPO, hold prognostic value in PAD.
- Further research is required to fully elucidate the role of neutrophils in the natural history of PAD.
Abstract:
Neutrophils play a role in cardiovascular (CV) disease. However, relatively scant evidence exists in the setting of peripheral artery disease (PAD). The aims of this study were to measure biomarkers of neutrophil activation in patients with symptomatic chronic PAD compared with healthy controls, to assess their association with PAD severity, and to evaluate their prognostic value in patients with PAD. The following circulating markers of neutrophil degranulation were tested: polymorphonuclear neutrophil (PMN) elastase, neutrophil gelatinase-associated lipocalin (NGAL), and myeloperoxidase (MPO). Neutrophil extracellular traps (NETs) were quantified by measuring circulating MPO-DNA complexes. Patients with PAD underwent a comprehensive series of vascular tests. The occurrence of 6-month major adverse CV (MACE) and limb events (MALE) was assessed. Overall, 110 participants were included, 66 of which had PAD. After adjustment for conventional CV risk factors, PMN-elastase (adjusted odds ratio [OR]: 1.008; 95% confidence interval [CI]: 1.002-1.015; p = 0.006), NGAL (adjusted OR: 1.045; 95%CI: 1.024-1.066; p < 0.001), and MPO (adjusted OR: 1.013; 95%CI: 1.001-1.024; p = 0.028) were significantly associated with PAD presence. PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95%CI: 1.000-1.020; p = 0.040) and MPO (adjusted HR: 1.027; 95%CI: 1.004-1.051; p = 0.019) were predictive of 6-month MACE and/or MALE. MPO displayed fair prognostic performance on receiver operating characteristic (ROC) curve analyses, with an area under the curve (AUC) of 0.74 (95%CI: 0.56-0.91) and a sensitivity and specificity of 0.80 and 0.65, respectively, for a cut-off of 108.37 ng/mL. MPO-DNA showed a weak inverse correlation with transcutaneous oximetry (TcPO2) on proximal foot (adjusted ρ -0.287; p = 0.032). In conclusion, in patients with symptomatic chronic PAD, enhanced neutrophil activity may be associated with an increased risk of acute CV events, rather than correlate with disease severity. Further research is needed to clarify the role of neutrophils in PAD natural history.
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