The Relationship Between Neutrophil–Lymphocyte Ratio and In-Stent Restenosis

The neutrophil–lymphocyte ratio (NLR) has been proposed as a prognostic marker in patients with peripheral arterial disease, and a high NLR has predictive value for future vascular events. ¹ Chang et al ² in their paper entitled “The Relationship Between the Neutrophil-Lymphocyte Ratio and In-Stent Restenosis in Patients With Femoropopliteal Chronic Total Occlusions” reported that the NLR is independently associated with early in-stent restenosis (ISR) in patients with femoropopliteal chronic total occlusions (CTO). We would like to comment on confounding factors.

First, inflammation is considered to play a key role in the pathophysiological process for many chronic diseases. ³ So, the investigators ² should consider that many inflammation-related diseases, like chronic obstructive pulmonary disease, ⁴ renal or hepatic dysfunction, and local or systemic infection, may influence the inflammatory state. ⁵ Therefore, these inflammatory diseases should be identified by appropriate diagnostic methods.

Second, many easily available inflammatory biomarkers including serum bilirubin, albumin, and resting heart rate may be independent risk factors for ISR and cardiovascular events. ^{6 –8} However, there were no data regarding those biological parameters in the study by Chang et al. ²

Third, the authors demonstrated that the higher baseline NLR was independently and positively associated with a higher risk of early ISR. ² In addition, the percentage of patients with diabetes mellitus (DM) in the early ISR group was significantly higher than that both in the non-ISR and late ISR groups, and the difference between early ISR and non-ISR groups was significant. Should DM have been considered as an independent risk factor for the occurrence of ISR? Diabetes mellitus is a vital factor in poor prognosis in patients who received cardiovascular interventional therapy. ⁹ Furthermore, DM was connected with restenosis in small femoropopliteal lesions. ¹⁰ Thus, DM should be considered to have an independent relationship with ISR in patients with femoropopliteal CTO.

In conclusion, NLR may have association with early ISR after stenting treatment in patients with femoropopliteal CTO. However, to identify factors associated with ISR after intervention, the comorbidities and health status of patients should be taken into consideration, particularly the effect of DM on ISR after stenting. Also, the combination of multiple inflammatory biomarkers may be helpful to assess the risk of ISR in patients who underwent stenting treatment for femoropopliteal CTO.