Is Elevated Neutrophil-to-Lymphocyte Ratio a Predictor of Stroke in Patients with Intermediate Carotid Artery Stenosis?

https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.10.031Get rights and content

Objective

An increased neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical prognosis in patients with cardiovascular disease. In this study, we aimed to investigate if there was a correlation between NLR and the risk of stroke in patients with intermediate carotid artery stenosis.

Methods

A total of 254 patients with a 50%-70% stenosis in the carotid artery, 115 of whom were symptomatic and 139 of whom were asymptomatic, were included in the study. Patients with a history of ischemic cerebrovascular event with or without sequelae, transient ischemic attack, and amaurosis fugax in the last 1-6 months were included in the symptomatic group of the study. The symptomatic and asymptomatic groups were compared in terms of total neutrophil count, lymphocyte count, and NLR.

Results

The total white blood cell count (WBC), neutrophil count, and NLR were found to be higher and the lymphocyte count was found to be lower in the symptomatic patients than those in the asymptomatic patients (symptomatic/asymptomatic, respectively, WBC [103/mm3]: 9.0/8.2, neutrophil count [103/mm3]: 6.1/5.0, NLR: 3.08/2.2, lymphocyte count [103/mm3]: 1.9/2.2) (P < .001). The cutoff value for NLR was found to be 2.6 or higher. In the multivariate regression analysis, an NLR value of 2.6 or higher was shown to be an independent variable for carotid artery stenosis to become symptomatic.

Conclusions

NLR is increased in symptomatic intermediate carotid artery stenosis. An increased NLR value is an independent variable for carotid artery plaques to become symptomatic.

Introduction

Atherosclerotic lesions are an important cause of ischemic stroke worldwide,1 accounting for approximately 10% of ischemic stroke cases in the United States and as much as 30%-40% of all incidents of ischemic stroke in Asia. Inflammation plays a role in all stages, from the onset of atherosclerosis to progression and subsequent rupture of the atherosclerotic plaque.2, 3 The main events in the physiopathology of atherogenesis are smooth muscle cell proliferation and lipid deposition in response to endothelial damage.4 Until recently, T lymphocytes and monocytes were considered to play prominent roles in atherogenesis as inflammatory cells. The significance of neutrophils was later demonstrated through observation of neutrophils in the atherosclerotic plaques of carotid arteries.5 Detection of early neutrophil infiltration in the atherosclerotic plaques allows prediction of the risk of plaque rupture.6, 7 Neutrophil predominance was demonstrated in rupture-prone lesions (larger lipid core, heavy macrophage influx, minor collagen, and smooth muscle cells) and neutrophils were shown to play a significant role in plaque destabilization.8, 9 A high rate of neutrophil elastase activity was also reported in histological investigations of the late-stage plaques formed in cerebral arteries.10

Neutrophils also affect platelets and increase aggregation.11 Activated neutrophils lead to plaque rupture through the effects of various proteolytic enzymes and myeloperoxidase-like oxidants.12, 13 In addition, neutrophils stimulate thrombogenesis by releasing tissue factors or inducing other cells to release tissue factors.14, 15 Currently, neutrophil-to-lymphocyte ratio (NLR) is considered to be a good marker that simultaneously shows the negative effects of neutrophil elevation as an indicator of acute inflammation and lymphocyte depletion as an indicator of physiological stress, as well as aids in the prediction of mortality and prognosis in stroke patients.16, 17

Severity of a carotid artery lesion is an important parameter that affects the risk of stroke. The risk of stroke increases with the severity of carotid artery lesion.18 To perform carotid artery intervention, the level of stenosis should angiographically be at least 50% in symptomatic patients and at least 70% in asymptomatic patients.19 In symptomatic patients, plaques that cause up to 50% stenosis in the carotid artery may pose a risk of recurrent stroke and requires surgical intervention or placement of a stent. We believe that a part of the plaques that cause asymptomatic intermediate carotid artery stenosis (50%-70%) may be associated with a higher risk of stroke. In this study, symptomatic and asymptomatic patients with intermediate carotid artery stenosis were compared in terms of total neutrophil count, lymphocyte count, and NLR.

Section snippets

Study Population

A total number of 312 patients were evaluated between December 2010 and January 2015 for enrollment in this prospective study. Fifty-eight patients were excluded from the study due to different causes and analyses were performed on the data obtained from 254 patients. The patients were divided into 2 groups as symptomatic (115 patients) and asymptomatic (139 patients) patients. The study was approved by the ethics committee of our institution. Patients who had 50%-70% stenosis in the carotid

Results

The demographic and clinical characteristics, in addition to the laboratory results of 254 patients (115 symptomatic and 139 asymptomatic) included in the study, are summarized in Table 1. The high-density lipoprotein level was found to be higher in the asymptomatic group than that in the symptomatic group. No difference was noted between the 2 groups with respect to the other parameters.

Comparison of hematological data between the 2 groups is shown in Table 2. Hemoglobin level and platelet

Discussion

This is the first study evaluating the value of inflammatory markers in predicting the risk of stroke associated with plaques that cause intermediate carotid artery stenosis. In the present study, the degree of stenosis in the carotid artery was evaluated by CDUS and CTA, and symptomatic and asymptomatic plaques were compared in terms of total neutrophil count, lymphocyte count, and the NLR. Our findings showed that the total neutrophil count and NLR were significantly higher and the total

Conclusion

NLR is increased in the presence of symptomatic intermediate carotid artery stenosis. NLR, which is an inexpensive and convenient marker, can be used as a predictor of stroke risk associated with carotid artery plaques causing intermediate stenosis.

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