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

Chung, Darda; Lee, Kee Ook; Choi, Jia; Kim, Nam Keun; Kim, Ok-Su; Kim, Sang-Heum; Oh, Seung-Hun; Kim, Won Chan

doi:10.3389/fneur.2020.01022

Cited by 22 publications

(12 citation statements)

References 48 publications

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“…Neutrophil-to-lymphocyte ratio, a biomarker indicating systemic inflammatory status, has been shown to be related to intracranial atherosclerosis. A study by Chung et al (29) revealed that high NLR was correlated with intracranial atherosclerosis (OR= 1.87; 95% CI, 1.15-3.06; P = 0.01) in healthy individuals, consistent with another study by Nam et al (15) indicating that NLR could be a predictor for the prevalence and burdens of ICAS. However, few studies revealed the independent predictive values of NLR in the prognosis of sICAS.…”

Section: Discussionsupporting

confidence: 76%

Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis

Ying

Feng

et al. 2021

Front. Neurol.

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Background: Neutrophil-to-lymphocyte ratio (NLR) is an indicator of poor prognosis in acute ischemic stroke (AIS), but associations between NLR with stroke severity and prognosis of intracranial atherosclerotic stenosis (ICAS)-related ischemic events have not been well-elucidated; therefore, we aimed to evaluate whether admission NLR levels correlate with the early stroke severity and short-term functional prognosis in patients with symptomatic intracranial atherosclerotic stenosis (sICAS).Methods: This retrospective study enrolled 899 consecutive patients with AIS attributed to ICAS at Xiangya Hospital stroke center between May 2016 and September 2020. The initial stroke severity was rated by the admission National Institutes of Health Stroke Scale (NIHSS) scores, and the short-term prognosis was evaluated using the 14-day modified Rankin Scale (mRS) scores after stroke onset. A severe stroke was defined as NIHSS >8; an unfavorable functional outcome was defined as mRS scores of 3–6. Admission NLR was determined based on circulating neutrophil and lymphocyte counts.Results: The median admission NLR of all patients was 2.80 [interquartile range (IQR), 2.00–4.00]. In univariate analysis, admission NLR was significantly elevated in patients with severe stroke and poor short-term prognosis. After multivariate adjustment, admission NLR levels were significantly correlated with severe stroke [odds ratio (OR), 1.132; 95% confidence interval (95% CI), 1.038–1.234; P = 0.005] and unfavorable short-term prognosis (OR, 1.102; 95% CI, 1.017–1.195; P = 0.018) in Model 1. In Model 2, the highest NLR tertile (≥3.533) remained an independent predictor of severe stroke (OR, 2.736; 95% CI, 1.590–4.708; P < 0.001) and unfavorable functional outcome (OR, 2.165; 95% CI, 1.416–3.311; P < 0.001) compared with the lowest NLR tertile (<2.231). The receiver operating characteristic (ROC) curves showed the predictability of NLR regarding the stroke severity [area under the curve (AUC), 0.659; 95% CI, 0.615–0.703; P < 0.001] and short-term prognosis (AUC, 0.613; 95% CI, 0.575–0.650; P < 0.001). The nomograms were constructed to create the predictive models of the severity and short-term outcome of sICAS.Conclusions: Elevated admission NLR levels were independently associated with the initial stroke severity and could be an early predictor of severity and poor short-term prognosis in AIS patients with ICAS, which might help us identify a target group timely for preventive therapies.

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Section: Discussionsupporting

confidence: 76%

Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis

Ying

Feng

et al. 2021

Front. Neurol.

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“…Moreover, Ying et al concluded that elevated admission NLR level was an independent factor associated with stroke severity and prognosis in symptomatic intracranial atherosclerosis patients ( 6 ). The relationship between extracranial large-artery stenosis and elevated NLR level was also reported by Chung et al in line with our results ( 35 ).…”

Section: Discussionsupporting

confidence: 93%

“…Our finding of high NLR level in intracranial stenosis is in accordance with previous studies. Chung et al have revealed that high NLR was correlated with intracranial large-artery atherosclerosis in individuals without neurological diseases ( 35 ). Nam et al also reported that NLR was associated with both prevalence and burdens of intracranial atherosclerosis in a healthy population ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Associations of neutrophil-to-lymphocyte ratio with intracranial and extracranial atherosclerotic stenosis

Xie

Liu²,

Dan³

et al. 2022

Front. Neurol.

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BackgroundNeutrophil-to-lymphocyte ratio (NLR) has been shown to be an important inflammatory maker. This study aims to investigate the association of NLR with intracranial and extracranial atherosclerotic stenosis.MethodsWe retrospectively recruited patients who underwent digital subtraction angiography (DSA) for evaluating intracranial/extracranial stenosis in the Zhongnan Hospital of Wuhan University from January 2017 to October 2021. Clinical characteristics, DSA data, blood routine, and lipid profile were recorded. Logistic regression was used to evaluate the association of NLR and intercranial/extracranial atherosclerotic stenosis in three aspects: distribution of stenosis, whether the stenosis is symptomatic, and degree of stenosis.ResultsA total of 1,129 patients were included in our analysis, with a median age of 62 y (interquartile range 55–68), and a median admission NLR of 2.39 (interquartile range 1.84–3.42). A total of 986 patients presented intracranial and/or extracranial atherosclerotic stenosis. Increased NLR were associated with intracranial stenosis [odds ratio (OR), 1.54; 95% CI, 1.27–1.85; p < 0.001], extracranial stenosis (OR, 1.56; 95% CI, 1.25–1.96; p < 0.001), and combined intracranial/extracranial stenosis (OR, 1.61; 95% CI, 1.28–2.03; p < 0.001). After adjustment of potential factors, higher NLR were independently associated with symptomatic stenosis (OR, 1.16; 95% CI, 1.05–1.27; p = 0.003) and degree of stenosis (OR, 1.32; 95% CI, 1.17–1.49; p < 0.001). Compared with the first quartile NLR, the second, third, and fourth quartiles NLR were independent risk factors for symptomatic stenosis and stenosis degree (both p for trend <0.001).ConclusionIncreased NLR is an important factor associated with both intracranial and extracranial atherosclerotic stenosis. Patients with symptomatic intracranial/extracranial atherosclerotic stenosis or a more severe degree of stenosis presented elevated NLR levels.

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“…Leukocytosis, including monocytosis, is a known risk factor for atherogenesis that can contribute to the imbalance of lesional leukocytes. 26 Upon WTD feeding, the ratio of blood neutrophils to lymphocytes was increased, suggesting WTD-induced systemic inflammation 27,28 that was not impacted by mouse genotype, sex, or models. Despite the difference in plasma cholesterol levels, cholesterol contents of resident peritoneal macrophages from male and female mice were similar between genotypes (Figure S6).…”

Section: Ilrun Deficiency Promotes In Situ Efferocytosis and Reduces ...mentioning

confidence: 99%

ILRUN Promotes Atherosclerosis Through Lipid-Dependent and Lipid-Independent Factors

Stankov

Lee

et al. 2022

ATVB

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BACKGROUND: Common genetic variation in close proximity to the ILRUN gene are significantly associated with coronary artery disease as well as with plasma lipid traits. We recently demonstrated that hepatic inflammation and lipid regulator with ubiquitin-associated domain-like and NBR1-like domain (ILRUN) regulates lipoprotein metabolism in vivo in mice. However, whether ILRUN, which is expressed in vascular cells, directly impacts atherogenesis remains unclear. We sought to determine the role of ILRUN in atherosclerosis development in mice. METHODS: For our study, we generated global Ilrun deficient ( Ilrun KO) male and female mice on 2 hyperlipidemic backgrounds: low density lipoprotein receptor knockout ( Ldlr KO) and apolipoprotein E knockout ( Apoe KO; double knockout [DKO]). RESULTS: Compared with littermate control mice (single Ldlr KO or Apoe KO), deletion of Ilrun in DKO mice resulted in significantly attenuated both early and advanced atherosclerotic lesion development, as well as reduced necrotic area. DKO mice also had significantly decreased plasma cholesterol levels, primarily attributable to non-HDL (high-density lipoprotein) cholesterol. Hepatic-specific reconstitution of ILRUN in DKO mice on the Apoe KO background normalized plasma lipids, but atherosclerotic lesion area and necrotic area remained reduced in DKO mice. Further analysis showed that loss of Ilrun increased efferocytosis receptor MerTK expression in macrophages, enhanced in vitro efferocytosis, and significantly improved in situ efferocytosis in advanced lesions. CONCLUSIONS: Our results support ILRUN as an important novel regulator of atherogenesis that promotes lesion progression and necrosis. It influences atherosclerosis through both plasma lipid-dependent and lipid-independent mechanisms. These findings support ILRUN as the likely causal gene responsible for genetic association of variants with coronary artery disease at this locus and suggest that suppression of ILRUN activity might be expected to reduce atherosclerosis.

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

Cited by 22 publications

References 48 publications

Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis

Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis

Associations of neutrophil-to-lymphocyte ratio with intracranial and extracranial atherosclerotic stenosis

ILRUN Promotes Atherosclerosis Through Lipid-Dependent and Lipid-Independent Factors

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