Abstract

Abstract Background/Introduction Neutrophil degranulation and neutrophil extracellular traps (NETs) are suggested to play a role in cardiovascular (CV) disease development [1]. Human studies showed that markers of NETs, are increased in patients with severe coronary atherosclerosis and predict risk of cardiac events [2]. The role of NETs in peripheral artery disease (PAD) has not been investigated. Purpose To measure circulating markers of neutrophil activity in patients with symptomatic PAD compared with matched healthy controls, evaluate their association with disease severity, and assess their prognostic value. Methods Multicenter, prospective case-control study. Circulating levels of polymorphonuclear neutrophil (PMN)-elastase, neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), and NETs-associated MPO-DNA complexes were measured in patients with symptomatic PAD and heathy controls. The former underwent comprehensive vascular evaluation including ankle-brachial index (ABI) calculation, transcutaneous oximetry measurement, constant-load treadmill test, 6-minute walking test, pulse wave velocity, and flow-mediated dilatation of the brachial artery. Six-month outcomes were: occurrence of major adverse CV (MACE) and limb events (MALE), ABI reduction ≥0.15, and 6-minute walking distance reduction ≥20 m. Results Overall, 110 participants were included, 66 had symptomatic PAD. Levels of all but one biomarker (MPO-DNA) were significantly higher in patients with PAD compared with healthy controls (Fig. 1). No significant correlation was found between biomarkers and vascular tests in patients with PAD. Baseline 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 MACE and/or MALE at 6-month follow-up in patients with symptomatic PAD (Table 1). Conclusions Present data show enhanced neutrophil activity, but not NETs levels, in patients with symptomatic PAD compared to controls. Baseline PMN-elastase and MPO levels were associated with worst CV outcome in patients with chronic PAD. These data suggest a role of neutrophils in PAD development and severity that needs to be further elucidated. Funding Acknowledgement Type of funding sources: None.

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