Blood Neutrophil/Lymphocyte Ratio Is Associated With Cerebral Large-Artery Atherosclerosis but Not With Cerebral Small-Vessel Disease

Abstract

Background and Objective: The blood neutrophil/lymphocyte ratio (NLR) is a marker of peripheral inflammation, with a high NLR associated with an increased risk of cardiovascular events and poor prognosis in ischemic stroke. However, few data are available on the differential impact of the blood NLR on different silent cerebral vascular pathologies, including cerebral large-artery atherosclerosis (LAA) and cerebral small-vessel disease (CSVD), in neurologically healthy individuals. Methods: We evaluated cardiovascular risk factors, brain magnetic resonance imaging (MRI), and MR angiography of 950 individuals without any neurological diseases. The study participants were divided into three groups according to NLR tertile (low, middle, and high). The presences of extracranial (EC) and intracranial (IC) atherosclerosis were considered to indicate LAA on brain MR angiography. The presences of silent lacunar infarction (SLI) and cerebral white matter hyperintensities (WMHs) were analyzed as indices of CSVD on brain MRI. Results: In univariate analysis, the high NLR tertile group showed a high prevalence of old age, hyperlipidemia, and renal dysfunction and higher fasting glucose. Multivariable logistic regression analysis revealed that indices of LAA (EC atherosclerosis [odds ratio: 1.88; 95% confidence interval: 1.14-3.09; p = 0.01] and IC atherosclerosis [odds ratio: 1.87; 95% confidence interval: 1.15-3.06; p = 0.01]) were more prevalent in the highest NLR tertile group than in the lowest NLR tertile group after adjustment for cardiovascular risk factors. However, no significant differences were found in the prevalence of CSVD indices (SLI and WMHs) among the three NLR tertile groups. Conclusions: A high NLR is associated with the development of cerebral LAA but not CSVD.

Keywords: cardiovascular risk factors; ischemic stroke; large-artery atherosclerosis; neutrophil-lymphocyte ratio; small-vessel disease.

Figure 1

Distributions of extracranial (EC) atherosclerosis, intracranial (IC) atherosclerosis, silent lacunar infarction (SLI), and cerebral white matter hyperintensities (WMHs) by serum neutrophil/lymphocyte ratio (NLR) levels categorized in tertiles. T1, lowest tertile; T2, middle tertile; T3, highest tertile.

Figure 2

Receiver operative characteristic curves and calibration plots of the models for extracranial (EC) atherosclerosis and intracranial (IC) atherosclerosis. (A) Receiver operative characteristic (ROC) curve of univariate logistic regression model for EC atherosclerosis with natural log-transformed serum neutrophil/lymphocyte ratio (logNLR). The black point shows optimal cut-off point of logNLR derived by Youden's method. The numbers in parentheses indicate specificity and sensitivity at the cut-off point (B) Comparison of area under curve (AUC) for EC atherosclerosis in the multivariate models with and without logNLR. Skyblue indicates AUC of the model with logNLR and orange indicates AUC of the model without logNLR. Adjustments were performed for the variables listed in Table 4. (C) Calibration plot for multivariate logistic regression with logNLR for EC atherosclerosis. (D) ROC curve of univariate logistic regression model for IC atherosclerosis with logNLR. (E) Comparison of AUC for IC atherosclerosis in the multivariate models with and without logNLR. (F) Calibration plot of the multivariate logistic regression with logNLR for IC atherosclerosis.