Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis.
Ying Yuanlin,Yu Fang,Luo Yunfang,Feng Xianjing,Liao Di,Wei Minping,Li Xi,Huang Qin,Liu Zeyu,Zhang Lin,Zhao Tingting,Tu Ruxin,Xia Jian
Frontiers in neurology
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). 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. 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; = 0.005] and unfavorable short-term prognosis (OR, 1.102; 95% CI, 1.017-1.195; = 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; < 0.001) and unfavorable functional outcome (OR, 2.165; 95% CI, 1.416-3.311; < 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; < 0.001] and short-term prognosis (AUC, 0.613; 95% CI, 0.575-0.650; < 0.001). The nomograms were constructed to create the predictive models of the severity and short-term outcome of sICAS. 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.
10.3389/fneur.2021.705949
Increase in neutrophils after recombinant tissue plasminogen activator thrombolysis predicts poor functional outcome of ischaemic stroke: a longitudinal study.
Shi J,Peng H,You S,Liu Y,Xu J,Xu Y,Liu H,Shi R,Cao Y,Liu C-F
European journal of neurology
BACKGROUND AND PURPOSE:Neutrophils, a pivotal immune responder to ischaemic brain insult, have been involved in neuroplasticity and increase after stroke. Recombinant tissue plasminogen activator (r-tPA), a promising treatment improving neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile of neutrophils after r-tPA treatment and their effect on neurological recovery after stroke are not well studied. METHODS:Cell counts of neutrophils, lymphocytes and their ratio (NLR) were measured on admission and 24 h after r-tPA infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age 64 years). Death or major disability at 3 months after stroke was diagnosed based on the modified Rankin Scale (mRS ≥ 3) obtained by neurologists who were blinded to any hospital records. The longitudinal associations of percentage increase in neutrophils, lymphocytes and the NLR with death or major disability were examined by logistic regression adjusting for covariates including neurological deficits at baseline. RESULTS:Neutrophils exhibited a steeper increase after r-tPA infusion in patients with death or major disability than in those without (P < 0.001). A 10% increase in neutrophils after r-tPA infusion was associated with an 83% increased risk for death or major disability within 3 months after stroke onset [odds ratio (OR) 1.99, P = 0.009]. Increased neutrophils at 24 h after r-tPA (OR 6.30, P < 0.001 after log transformation) but not on admission significantly predicted increased risks for death or major disability within 3 months after stroke onset. A similar phenomenon was also observed for the NLR. CONCLUSIONS:A dynamic increase in neutrophils after stroke significantly predicts 3-month death or major disability in acute ischaemic stroke patients receiving r-tPA treatment.
10.1111/ene.13575
Prognostic value of the neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis.
Wang Chengbing,Zhang Qian,Ji Mingwei,Mang Jing,Xu Zhongxin
BMC neurology
BACKGROUND:The relationship between the neutrophil-to-lymphocyte ratio (NLR) and poor prognostics in acute ischemic stroke (AIS) patients who receive intravenous thrombolysis (IVT) remains controversial. The purpose of this systematic review and meta-analysis was to evaluate the association between the NLR and poor prognosis after IVT. Furthermore, we aimed to determine whether the NLR at admission or post-IVT plays a role in AIS patients who received IVT. METHODS:The PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases were searched for relevant articles until October 7, 2020. Cohort and case-control studies were included if they were related to the NLR in AIS patients treated with IVT. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were pooled to estimate the relationship between NLR and poor prognosis after IVT. A random effects model was used to calculate the pooled data. RESULTS:Twelve studies, including 3641 patients, met the predefined inclusion criteria. Higher NLRs were associated with an increased risk of hemorrhagic transformation (HT) (OR = 1.33, 95 % CI = 1.14-1.56, P < 0.001) and a poor 3-month functional outcome (OR = 1.64, 95 % CI = 1.38-1.94, P < 0.001) in AIS patients who received IVT. Subgroup analysis suggested that the NLR at admission rather than post-IVT was associated with a higher risk of HT (OR = 1.33, 95 % CI = 1.01-1.75, P = 0.039). There was no statistically significant difference between higher NLRs and 3-month mortality (OR = 1.14, 95 % CI = 0.97-1.35, P = 0.120). CONCLUSIONS:A high NLR can predict HT and poor 3-month functional outcomes in AIS patients who receive IVT. The NLR at admission rather than the post-IVT NLR was an independent risk factor for an increased risk of HT after IVT.
10.1186/s12883-021-02222-8
Atrial Fibrillation is Strongly Associated With the Neutrophil to Lymphocyte Ratio in Acute Ischemic Stroke Patients: A Retrospective Study.
Journal of clinical laboratory analysis
BACKGROUND:No study has investigated the relationship between hospital-admission neutrophil and lymphocyte ratio (NLR) and various stroke risk factors. We sought to determine which stroke risk factor could be the most appropriate predictor of NLR in acute ischemic stroke. METHODS:We collected data on various stroke risk factors and National Institutes of Health Stroke Scale (NIHSS) score in 1,053 acute ischemic stroke patients. The regression analysis was adjusted for confounding factors such as stroke risk factors. RESULTS:There was a trend of increased NLR with a rise in alcohol consumption, the prevalence of hypertension, cardioembolism (CE) etiology, the NIHSS scores in men and the prevalence of atrial fibrillation, other heart diseases, CE and small vessel occlusion etiology and the NIHSS scores in women. Multiple linear regression analyses, adjusted for confounding factors, showed that the atrial fibrillation and NIHSS scores in men and atrial fibrillation, diabetes mellitus as well as NIHSS scores in women had a significant positive association with NLR. However, a negative association was showed for body mass index (BMI). CONCLUSION:We confirmed that the atrial fibrillation can be a predictor of high NLR in acute stroke patients, and diabetes mellitus as well as low BMI could be a predictor of high NLR in female acute ischemic stroke patients.
10.1002/jcla.22041
The Relationship between Neutrophil-to-Lymphocyte Ratio and Intracerebral Hemorrhage in Type 2 Diabetes Mellitus.
Luo Peng,Li Rui,Yu Siyuan,Xu Tingting,Yue Shufan,Ji Yongli,Chen Xin,Xie Haiting
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
INTRODUCTION:Chronic systematic inflammation has been suggested to be associated with the occurrence and development of cardiovascular events. Low-grade systematic inflammation persists in type 2 diabetes mellitus (T2DM) patients. In addition, the risk of cerebral hemorrhage in these patients is increased compared with non-diabetic patients. Neutrophil-to-lymphocyte ratio (NLR) is the ratio derived by dividing the neutrophil count with the lymphocyte count from a peripheral blood sample. This study aimed to explore the relation between NLR and cerebral hemorrhage, and to prove that NLR is an independent risk factor of cerebral hemorrhage in T2DM patients. METHODS:In total, 429 cases of T2DM patients were included. The patients were divided into two groups depending on the presence of cerebral hemorrhage: the cerebral hemorrhage group (n = 87) and the control group (n = 342). Based on clinical and laboratory data of diabetes diagnosis, this article investigates the relationship between NLR and the risk of cerebral hemorrhage. RESULTS:Increase in NLR was positively correlated with the incidence of cerebral hemorrhage in T2DM patients and might serve as an independent risk factor of cerebral hemorrhage in T2DM patients (OR: 4.451, 95% CI: 2.582-7.672). NLR >2.58 might be useful in predicting the threshold value of cerebral hemorrhage risk in newly diagnosed T2DM patients (area under the curve: .72, 95% CI: .659-.780, P < .001) CONCLUSION: As an indicator of the degree of systematic inflammation, NLR is an independent risk factor of cerebral hemorrhage in T2DM patients.
10.1016/j.jstrokecerebrovasdis.2016.10.041
Neutrophil to lymphocyte ratio as an indicative of diabetic control level in type 2 diabetes mellitus.
African health sciences
BACKGROUND:Type 2 diabetes mellitus is associated with chronic low grade inflammation. One of the novel inflammatory markers is hemogram derived neutrophil to lymphocyte ratio (NLR). OBJECTIVE:We aimed to compare NLR levels of diabetic subjects and healthy controls and to observe possible correlation between NLR and HbA1c. METHODS:Medical data of type 2 diabetic subjects admitted to out-patient clinics of our institution between April to July in 2017 were obtained from database and retrospectively analyzed. Control group was chosen from healthy subjects who visited our institution for a routine check-up. Anthropometric measures, laboratory data, including, HbA1c, NLR were recorded. RESULTS:Median NLR of the type 2 DM group 2.44 (1.9) was significantly elevated when compared to healthy controls (1.5 (0.9), (p<0.001). In addition, a Pearson's correlation test revealed that NLR was strongly correlated with age (r=0.26, p=0.008), fasting plasma glucose (r=0.38, p<0.001), and HbA1c (r=0.49, p<0.001). CONCLUSION:Elevated NLR in otherwise healthy subjects may be indicative of underlying impaired glucose metabolism and moreover, NLR should be used as a marker of diabetic control level in addition to HbA1c in type 2 diabetic subjects.
10.4314/ahs.v19i1.35
Neutrophil to lymphocyte ratio and risk of a first episode of stroke in patients with atrial fibrillation: a cohort study.
Journal of thrombosis and haemostasis : JTH
BACKGROUND:The neutrophil to lymphocyte ratio (NLR) is associated with increased risk of cardiovascular morbidity and mortality. We aimed to assess the association between NLR and first episode of stroke in patients with atrial fibrillation. METHODS:Using the computerized database of the largest HMO in Israel, we identified a cohort of adults, aged 20 years or older, with atrial fibrillation diagnosed before 1 January 2012. Eligible subjects had no prior stroke or TIA, were not on anticoagulants at baseline, and had at least one blood cell count performed in 2011. The cohort (32,912 subjects) was followed for the first event of stroke or TIA until 31 December 2012. RESULTS:Overall 981 subjects developed stroke during a follow-up of 30,961 person-years (stroke rate, 3.17 per 100 person-years). The incidence rate of stroke increased across NLR quartiles: 2.27, 2.72, 3.26 and 4.54 per 100 person-years, respectively. Cox proportional hazard regression analysis adjusting for the individual CHA2 DS2 -VASc score risk factors showed that, compared with the lowest NLR quartile, the HR for stroke was 1.11 (95% CI, 0.91-1.35), 1.25 (1.03-1.51) and 1.56 (1.29-1.88) for the second, third and highest quartile, respectively. On stratified analysis, NLR refined the risk of stroke across all CHA2 DS2 -VASc score strata. Adding NLR to the CHA2 DS2 -VASc score increased the AUC from 0.627 (95% CI, 0.612-0.643) to 0.635 (0.619-0.651) (P = 0.037). CONCLUSIONS:The neutrophil to lymphocyte ratio is directly associated with the risk of stroke in patients with atrial fibrillation. Future studies are needed to replicate these findings.
10.1111/jth.13006
Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury.
Povroznik Jessica M,Engler-Chiurazzi Elizabeth B,Nanavati Tania,Pergami Paola
SAGE open medicine
OBJECTIVES:This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. METHODS:A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke (n = 15), and transient tachypnea of the newborn (n = 48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0-12, 12-36, and 36-60 h after birth) were collected, and neutrophil-to-lymphocyte ratio was calculated. RESULTS:Hypoxic-ischemic encephalopathy + total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy + total-body cooling) revealed that absolute lymphocyte count changes occurring at 0-12 h are likely due to disease progression, rather than total-body cooling treatment. CONCLUSION:These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxic-ischemic encephalopathy in neonates is warranted.
10.1177/2050312117752613
Augmented Brain Infiltration and Activation of Leukocytes After Cerebral Ischemia in Type 2 Diabetic Mice.
Frontiers in immunology
Stroke patients with diabetes suffer from higher mortality rate and worsened neurological outcome. However, the responses of immune system to cerebral ischemia in the setting of diabetes remain poorly understood. In this study, we investigated the temporal profile of leukocyte mobilization and brain infiltration following distal middle cerebral artery occlusion (dMCAO) in db/db mouse model of type 2 diabetes (T2D) and its db/+ normoglycemic controls. We found a significant increase of brain-infiltrating CD4 T cell at day 3 after dMCAO, and a delayed and dramatic increase of brain-infiltrating neutrophils, CD4 T cells, CD8 T cells, and B cells at day 7 after dMCAO in db/db mice vs. db/+ controls. Leukocyte subsets in the circulation and spleen were also measured, however, there is no significant difference between non-diabetic and diabetic groups. Furthermore, we identified an increased expression of activation marker CD69 in brain-infiltrating neutrophils, CD4 T and CD8 T cells, and IFN-γ in brain-infiltrating CD4 T cells in db/db mice at day 7 after dMCAO. These findings for the first time demonstrate that cerebral ischemia induces a delayed and sustained augmentation of brain infiltration and activation of neutrophils and lymphocytes in type 2 diabetic mice and these altered immune responses might contribute to the severer brain tissue damage and worse neurological outcomes of diabetes stroke, which warrants further investigation.
10.3389/fimmu.2019.02392
Neutrophil-to-Lymphocyte Ratio Is a Prognostic Marker in Acute Ischemic Stroke.
Xue Jie,Huang Wensi,Chen Xiaoli,Li Qian,Cai Zhengyi,Yu Tieer,Shao Bei
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:Neutrophil-to-lymphocyte ratio is an independent predictor of mortality in patients with acute ischemic stroke. However, it is uncertain whether neutrophil-to-lymphocyte ratio is related with functional outcome and recurrent ischemic stroke. In this study, we aimed to investigate the relationship of neutrophil-to-lymphocyte ratio with stroke severity, functional outcome, and recurrent ischemic stroke after acute ischemic stroke. METHODS:A total of 280 patients with acute ischemic stroke were included in the study. Patients were divided into 3 groups according to the neutrophil-to-lymphocyte ratio value (<2, 2-3, >3). Demographic, clinical, and laboratory data were collected for all patients. We evaluated the association between neutrophil-to-lymphocyte ratio and (1) stroke severity on admission, (2) functional outcome at 3 months, and (3) recurrent ischemic stroke. Regression analyses were performed, adjusting for confounders. RESULTS:After adjustment for potential confounders, neutrophil-to-lymphocyte ratio was associated with an increased risk of stroke severity on admission (odds ratio [OR] 1.364, 95% confidence interval [CI] 1.101-1.690, P = .005) and primary unfavorable outcome (OR 1.455, 95% CI 1.083-1.956, P = .013). After a median of 1.13 years (interquartile range.91-1.42) of follow-up, neutrophil-to-lymphocyte ratio was associated with recurrent ischemic stroke after adjustment (hazard ratio 1.499, 95% CI 1.161-1.935, P = .002). CONCLUSIONS:Our study suggests that neutrophil-to-lymphocyte ratio is associated with stroke severity on admission, primary unfavorable functional outcome, and recurrent ischemic stroke in patients with acute ischemic stroke.
10.1016/j.jstrokecerebrovasdis.2016.11.010
Neutrophil-lymphocyte ratio in acute ischemic stroke: Immunopathology, management, and prognosis.
Sharma Divyansh,Spring Kevin J,Bhaskar Sonu Menachem Maimonides
Acta neurologica Scandinavica
There is an ongoing need for accurate prognostic biomarkers in the milieu of acute ischemic stroke (AIS) receiving reperfusion therapy. Neutrophil-lymphocyte ratio (NLR) has been implicated in emergency medicine and acute stroke setting as an important biomarker in the prognosis of patients. However, there are ongoing questions around its accuracy and translation into clinical practice given suboptimal sensitivity and specificity results, as well as varying thresholds and lack of clarity around which NLR time points are most clinically indicative. This article provides a comprehensive overview of the role of NLR in AIS patients receiving reperfusion therapy and perspectives on areas of future research. NLR may be an important biomarker in risk stratifying patients in AIS to identify and select those who are more likely to benefit from reperfusion therapy. Appropriate clinical decision-making tools and models are required to harness the predictive value of NLR, which could be useful in identifying and monitoring high-risk patients to guide early treatment and achieve improved outcomes. Our understanding of the role of NLR in the immunopathogenesis of AIS is also suboptimal, which hinders the ability to translate this into clinical practice.
10.1111/ane.13493