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脑卒中已经成为我国首位致残和死亡的原因,严重影响我国居民的身体健康。缺血性脑卒中是最为常见的脑卒中类型。目前,大量临床研究证实早期使用阿替普酶(rt-PA)进行静脉溶栓治疗能够明显改善急性缺血性脑卒中病人临床症状和临床预后[1]。然而,并非所有病人都能达到较好的临床治疗效果。国内有研究[2]调查发现,采用静脉溶栓后,部分病人预后并不理想。因此,有必要在病人治疗期间采用相关的评判标准对其治疗效果及出院结局进行评估和预判,寻找可能预测溶栓预后效果的指标,为治疗和康复提供参考。本研究对rt-PA溶栓治疗的急性缺血性脑卒中病人临床预后的相关因素进行了研究,发现了中性粒细胞与淋巴细胞比值(NLR)对溶栓治疗效果具有一定的预测作用。现作报道。
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ΔNIHSS评分预后差组的高血压和房颤人数比例均高于ΔNIHSS评分预后较好组(P < 0.01和P < 0.05),ΔNIHSS评分预后差组的白细胞、中性粒细胞、NLR水平均高于ΔNIHSS评分预后较好组(P < 0.01),其余指标2组间差异无统计学意义(P>0.05)(见表 1)。
指标 预后较差组(n=65) 预后较好组(n=122) χ2 P 年龄/岁 68.05±3.12 66.68±5.66 0.77* >0.05 抽烟 24 30 3.04 >0.05 饮酒 15 19 1.25 >0.05 糖尿病 12 36 4.17 >0.05 冠心病 12 22 0.05 >0.05 高血压 50 67 8.76 < 0.01 房颤 15 13 5.13 < 0.05 发病到医院时间/h 111.74±6.98 108.58±5.69 0.38* >0.05 入院到溶栓时间/h 48.61±12.36 46.88±9.63 0.55* >0.05 白细胞/(×109/L) 8.63±1.39 7.32±2.30 2.69* < 0.01 中性粒细胞/(×109/L) 6.15±0.65 4.85±0.69 2.86* < 0.01 淋巴细胞/(×109/L) 1.85±0.14 1.87±0.08 0.12* 0.905 NLR 4.89±0.37 3.19±0.25 2.95* < 0.01 血小板/(×109/L) 210.49±36.52 207.40±35.45 0.37* >0.05 同型半胱氨酸/(μmol/L) 18.70±2.08 18.81±3.57 0.04* >0.05 高密度脂蛋白/(mmol/L) 1.37±0.08 1.33±0.06 0.35* >0.05 低密度脂蛋白/(mmol/L) 2.98±0.85 4.07±1.23 0.62* >0.05 胆固醇/(mmol/L) 4.73±1.21 4.42±1.14 1.69* >0.05 三酰甘油/(mmol/L) 1.73±0.25 2.12±0.13 1.86* >0.05 尿酸/(μmol/L) 341.77±20.58 356.04±22.78 0.08* >0.05 随机血糖/(mmol/L) 8.31±1.25 8.71±1.54 0.61* >0.05 C反应蛋白/(μg/mL) 7.75±0.87 8.39±0.63 0.43* >0.05 D二聚体/(mg/L) 0.68±0.11 0.52±0.06 1.31* >0.05 *示t值 表 1 ΔNIHSS评分预后较差组和预后较好组临床指标的比较(x±s)
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ΔMRS评分预后差组的房颤人数比例高于ΔMRS评分预后较好组(P < 0.05),ΔMRS评分预后差组的白细胞、中性粒细胞、NLR水平均高于ΔMRS评分预后较好组(P < 0.01),其余指标2组间差异无统计学意义(P>0.05)(见表 2)。
指标 预后较差组(n=68) 预后较好组(n=119) χ2 P 年龄/岁 69.74±3.62 67.19±4.32 1.39* >0.05 抽烟 15 41 0.71 >0.05 饮酒 11 24 0.11 >0.05 糖尿病 11 37 2.13 >0.05 冠心病 13 24 0.33 >0.05 高血压 39 87 0.02 >0.05 房颤 16 12 6.14 < 0.05 发病到医院时间/h 113.83±36.24 107.95±38.25 0.70* >0.05 入院到溶栓时间/h 51.28±8.21 45.73±9.25 1.74* >0.05 白细胞/(×109/L) 8.81±4.13 7.41±2.71 2.67* < 0.01 中性粒细胞/(×109/L) 6.45±1.36 4.89±1.54 3.15* < 0.01 淋巴细胞/(×109/L) 1.70±0.14 1.92±0.10 1.35* >0.05 NLR 5.69±1.85 3.30±0.99 3.43* < 0.01 血小板/(×109/L) 196.20±33.24 210.76±35.48 1.67* >0.05 同型半胱氨酸/(μmol/L) 18.12±1.89 18.93±1.56 0.30* >0.05 高密度脂蛋白/(mmol/L) 1.37±0.05 1.35±0.04 0.26* >0.05 低密度脂蛋白/(mmol/L) 2.68±0.17 3.89±0.25 0.50* >0.05 胆固醇/(mmol/L) 4.62±0.16 4.52±0.12 0.52* >0.05 三酰甘油/ mmol/L 1.62±0.11 1.93±0.12 1.69* >0.05 尿酸/(μmol/L) 353.98±55.69 350.49±60.24 0.21* >0.05 随机血糖/(mmol/L) 8.62±3.25 8.55±2.34 0.09* >0.05 C反应蛋白/(μg/mL) 7.69±1.05 8.67±1.37 0.57* >0.05 D二聚体/(mg/L) 0.70±0.04 0.60±0.08 0.68* >0.05 表 2 ΔMRS评分预后较差组和预后较好组临床资料的比较(x±s)
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Spearman相关分析结果显示, 与ΔNIHSS呈负相关的指标有高血压(rs=-0.169,P < 0.05)、房颤(rs=-0.230,P < 0.01)、白细胞(rs=-0.170,P < 0.05)、中性粒细胞(rs=-0.189,P < 0.05)、NLR (rs=-0.176,P < 0.05);与ΔMRS呈负相关的指标有房颤(rs=-0.194,P < 0.05)和NLR(rs=-0.156,P < 0.05)。
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以溶栓后ΔNIHSS评分为因变量,单因素分析有差异的变量为自变量,自变量高血压和房颤为二分类变量,设置哑变量(有高血压数值为1,否为0;有房颤数值为1,否为0),采用逐步回归进行线性回归分析(进入水准为α=0.05,剔除水准为α=0.1)。结果显示,线性回归方程成立(F=6.12,P < 0.05,R2=0.128),NLR和高血压与ΔNIHSS评分呈负相关关系(P < 0.05)(见表 3)。
因变量 自变量 b SE B t P ΔNIHSS NLR -0.173 0.070 -0.206 2.46 < 0.05 高血压 -1.535 0.644 -0.200 2.39 < 0.05 ΔMRS NLR -0.072 0.036 -0.175 2.01 < 0.05 表 3 回归分析
以溶栓后ΔMRS评分为因变量,单因素分析有差异的变量为自变量,自变量房颤为二分类变量,设置哑变量(有房颤数值为1,否为0)采用逐步回归进行线性回归分析(进入水准为α=0.05,剔除水准为α=0.1)。结果显示,线性回归方程成立(F=4.033,P < 0.05,R2=0.031);只有NLR进入的回归方程,NLR与ΔMRS评分呈负相关关系(P < 0.03)(见表 4)。
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以ΔNIHSS < 2预后较差和ΔNIHSS≥2预后较好为结局变量,分析NLR的预测效度。结果显示,ROC曲线下面积为0.595 (P < 0.05),最佳临界值5.169,敏感度0.879,特异性0.302,约登指数0.181(见图 1)。
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以ΔMRS差值< 3预后较差和ΔMRS≥3预后较好为结局变量,分析NLR的预测效度。结果显示,ROC曲线下面积为0.618 (P < 0.05),最佳临界值6.228,敏感度0.917,特异性0.327,约登指数0.244(见图 2)。
缺血性脑卒中rt-PA溶栓效果的影响因素分析和NLR的预测作用研究
Influencing factors analysis of rt-PA thrombolytic therapy and investigation of NLR predictive effect in ischemic stroke
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摘要:
目的研究缺血性脑卒中急诊阿替普酶(rt-PA)溶栓病人的预后影响因素,探讨溶栓前中性粒细胞与淋巴细胞比值(NLR)对溶栓预后的预测价值。 方法选择行急诊rt-PA溶栓治疗的缺血性脑卒中病人187例,收集可能与缺血性脑卒中预后相关的影响因素,跟踪随访并收集不同时间段的NIHSS评分和MRS评分,分别将溶栓前NIHSS评分减去溶栓后2周NIHSS评分,减分值ΔNIHSS < 2为预后较差组(65例),ΔNIHSS≥2为预后较好组(122例);将溶栓前MRS评分减去溶栓后3个月MRS评分,减分值ΔMRS差值< 3为预后较差组(68例),ΔMRS≥3为预后较好组(119例),并分析溶栓预后效果的影响因素和可能发挥预测作用的指标。 结果ΔNIHSS评分预后差组的高血压和心房颤动人数比例高于ΔNIHSS评分预后较好组(P < 0.01和P < 0.05),ΔNIHSS评分预后差组的白细胞、中性粒细胞、NLR水平高于ΔNIHSS评分预后较好组(P < 0.01)。ΔMRS评分预后差组的心房颤动人数比例高于ΔMRS评分预后较好组(P < 0.05),ΔMRS评分预后差组的白细胞、中性粒细胞、NLR水平高于ΔMRS评分预后较好组(P < 0.01)。进一步相关分析和线性回归分析显示,NLR分别是溶栓后ΔNIHSS评分(b=-0.173,t=2.46,P < 0.05)和以溶栓后ΔMRS评分(b=0.072,t=2.01,P < 0.05)的独立影响因素。ROC曲线分析显示NLR可以分别作为ΔNIHSS (AUC=0.595,P < 0.05,最佳临界值5.169)和ΔMRS (AUC=0.618,P < 0.05,最佳临界值6.228)预后的预测指标。 结论溶栓前NLR水平是缺血性脑卒中病人rt-PA溶栓治疗预后的独立影响因素,并且可以作为溶栓治疗效果的潜在的预测参考指标。 -
关键词:
- 缺血性脑卒中 /
- 阿替普酶溶栓 /
- 影响因素 /
- 中性粒细胞与淋巴细胞比值 /
- 预测指标
Abstract:ObjectiveTo study the prognostic factors of patients with ischemic stroke after emergency rt-PA thrombolytic therapy and explore the predictive value of neutrophil to lymphocyte ratio(NLR). MethodsA total of 187 patients with ischemic stroke who received emergency rt-PA thrombolytic therapy were selected, the influencing factors that might be related to the prognosis of ischemic stroke were collected.NIHSS score and MRS score at different time points were followed up and collected.The NIHSS score before thrombolysis was subtracted from the NIHSS score 2 weeks after thrombolysis.ΔNIHSS < 2 was considered as poor prognosis group (65 patients), and Δ NIHSS ≥ 2 was considered as good prognosis group (122 patients).The MRS score before thrombolysis was subtracted from the MRS score 3 months after thrombolysis.ΔMRS < 3 was considered as poor prognosis group (68 patients), and ΔMRS ≥ 3 was considered as good prognosis group (119 patients).Independent sample T test, Spearman correlation analysis, linear regression analysis and ROC curve analysis were used, respectively.The factors influencing the prognostic effect of thrombolytic therapy and the possible predictive indicators were analyzed. ResultsThe proportions of patients with hypertension and atrial fibrillation in the poor ΔNIHSS score group were higher than that in the better ΔNIHSS score group (P < 0.01 and P < 0.05).The levels of leukocyte, neutrophils and NLR in the poor ΔNIHSS score group were higher than those in the better ΔNIHSS score group (P < 0.01).The proportion of patients with atrial fibrillation in the poor ΔMRS score group was higher than that in the better ΔMRS score group (P < 0.05).The levels of leukocyte, neutrophils and NLR in the poor ΔMRS score group were higher than those in the better ΔMRS score group (P < 0.01).Further correlation analysis and linear regression analysis showed that NLR was significantly associated with ΔNIHSS score (b=-0.173, t=2.46, P < 0.05) and ΔMRS score (b=0.072, t=2.01, P < 0.05) after thrombolysis.ROC curve analysis showed that NLR could be used as the predictor of ΔNIHSS (AUC=0.595, P < 0.05, the optimal cutoff value was 5.169) and ΔMRS (AUC=0.618, P < 0.05, the optimal cutoff value was 6.228). ConclusionsNLR level before thrombolytic therapy is an independent factor which influencing the prognosis of patients with ischemic stroke after rt-PA thrombolytic therapy, and it can be used as a potential reference index to predict the efficacy of thrombolytic therapy. -
Key words:
- ischemic stroke /
- rt-PA thrombolysis /
- influence factors /
- neutrophil to lymphocyte ratio /
- predictor
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表 1 ΔNIHSS评分预后较差组和预后较好组临床指标的比较(x±s)
指标 预后较差组(n=65) 预后较好组(n=122) χ2 P 年龄/岁 68.05±3.12 66.68±5.66 0.77* >0.05 抽烟 24 30 3.04 >0.05 饮酒 15 19 1.25 >0.05 糖尿病 12 36 4.17 >0.05 冠心病 12 22 0.05 >0.05 高血压 50 67 8.76 < 0.01 房颤 15 13 5.13 < 0.05 发病到医院时间/h 111.74±6.98 108.58±5.69 0.38* >0.05 入院到溶栓时间/h 48.61±12.36 46.88±9.63 0.55* >0.05 白细胞/(×109/L) 8.63±1.39 7.32±2.30 2.69* < 0.01 中性粒细胞/(×109/L) 6.15±0.65 4.85±0.69 2.86* < 0.01 淋巴细胞/(×109/L) 1.85±0.14 1.87±0.08 0.12* 0.905 NLR 4.89±0.37 3.19±0.25 2.95* < 0.01 血小板/(×109/L) 210.49±36.52 207.40±35.45 0.37* >0.05 同型半胱氨酸/(μmol/L) 18.70±2.08 18.81±3.57 0.04* >0.05 高密度脂蛋白/(mmol/L) 1.37±0.08 1.33±0.06 0.35* >0.05 低密度脂蛋白/(mmol/L) 2.98±0.85 4.07±1.23 0.62* >0.05 胆固醇/(mmol/L) 4.73±1.21 4.42±1.14 1.69* >0.05 三酰甘油/(mmol/L) 1.73±0.25 2.12±0.13 1.86* >0.05 尿酸/(μmol/L) 341.77±20.58 356.04±22.78 0.08* >0.05 随机血糖/(mmol/L) 8.31±1.25 8.71±1.54 0.61* >0.05 C反应蛋白/(μg/mL) 7.75±0.87 8.39±0.63 0.43* >0.05 D二聚体/(mg/L) 0.68±0.11 0.52±0.06 1.31* >0.05 *示t值 表 2 ΔMRS评分预后较差组和预后较好组临床资料的比较(x±s)
指标 预后较差组(n=68) 预后较好组(n=119) χ2 P 年龄/岁 69.74±3.62 67.19±4.32 1.39* >0.05 抽烟 15 41 0.71 >0.05 饮酒 11 24 0.11 >0.05 糖尿病 11 37 2.13 >0.05 冠心病 13 24 0.33 >0.05 高血压 39 87 0.02 >0.05 房颤 16 12 6.14 < 0.05 发病到医院时间/h 113.83±36.24 107.95±38.25 0.70* >0.05 入院到溶栓时间/h 51.28±8.21 45.73±9.25 1.74* >0.05 白细胞/(×109/L) 8.81±4.13 7.41±2.71 2.67* < 0.01 中性粒细胞/(×109/L) 6.45±1.36 4.89±1.54 3.15* < 0.01 淋巴细胞/(×109/L) 1.70±0.14 1.92±0.10 1.35* >0.05 NLR 5.69±1.85 3.30±0.99 3.43* < 0.01 血小板/(×109/L) 196.20±33.24 210.76±35.48 1.67* >0.05 同型半胱氨酸/(μmol/L) 18.12±1.89 18.93±1.56 0.30* >0.05 高密度脂蛋白/(mmol/L) 1.37±0.05 1.35±0.04 0.26* >0.05 低密度脂蛋白/(mmol/L) 2.68±0.17 3.89±0.25 0.50* >0.05 胆固醇/(mmol/L) 4.62±0.16 4.52±0.12 0.52* >0.05 三酰甘油/ mmol/L 1.62±0.11 1.93±0.12 1.69* >0.05 尿酸/(μmol/L) 353.98±55.69 350.49±60.24 0.21* >0.05 随机血糖/(mmol/L) 8.62±3.25 8.55±2.34 0.09* >0.05 C反应蛋白/(μg/mL) 7.69±1.05 8.67±1.37 0.57* >0.05 D二聚体/(mg/L) 0.70±0.04 0.60±0.08 0.68* >0.05 表 3 回归分析
因变量 自变量 b SE B t P ΔNIHSS NLR -0.173 0.070 -0.206 2.46 < 0.05 高血压 -1.535 0.644 -0.200 2.39 < 0.05 ΔMRS NLR -0.072 0.036 -0.175 2.01 < 0.05 -
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