血清天冬酰胺内肽酶与急性大动脉粥样硬化型卒中间相关性的前瞻性研究

doi:10.16150/j.1671-2870.2021.02.012

摘要/Abstract

摘要：

目的:探讨血清天冬酰胺内肽酶（legumain,LGMN）与急性大动脉粥样硬化（large-artery atherosclerosis, LAA）型卒中患者早期神经功能恶化（early neurological deterioration, END）间的相关性。方法:前瞻性纳入334例急性LAA型卒中患者,检测其血清LGMN水平。END定义为入院3 d内任意时间点复评美国国立卫生研究院卒中量表（National Institute of Health Stroke Scale,NIHSS）评分较入院时增加≥2分。将患者按照入院后有无发生END进行分组比较,建立Logistic回归模型分析确定END发生的独立危险因素。采用受试者操作特征（receiver operator characteristic,ROC）曲线分析血清LGMN预测患者发生END的价值。结果:334例LAA型卒中患者中有78例（23.4%）发生END,作为END组,余256例为非END组。单因素结果分析显示,END组的LGMN水平、年龄、合并疾病（高血压、糖尿病、高血脂）比例、存在易损斑块的比例、入院收缩压水平、入院NIHSS评分和空腹血糖、糖化血红蛋白、超敏C反应蛋白水平均高于非END组,差异均有统计学意义（P均<0.05）。END患者中,中度狭窄组（7.05 μg/L）及闭塞组（6.80 μg/L）的血清LGMN水平显著低于重度狭窄组（8.66 μg/L）（P<0.05）。多因素Logistic回归分析结果显示,血清LGMN水平升高是患者发生END的独立危险因素[优势比（odds ratio,OR）=1.309,95% 置信区间（confidence interval,CI）为1.188~1.441,P<0.001）],其他危险因素还包括存在易损斑块、入院收缩压高、糖化血红蛋白水平高以及入院NIHSS评分高。ROC曲线分析结果显示,血清LGMN预测END的曲线下面积为0.715（95%CI为0.663~0.763,P<0.001）,此时最佳临界值为6.73 μg/L。结论:LGMN水平升高是急性LAA型卒中患者发生END的独立危险因素,可能可作为预测END的新型生物标志物。

关键词: 卒中, 天冬酰胺内肽酶, 早期神经功能恶化

Abstract:

Objective: To investigate the correlation between legumain(LGMN) and early neurological deterioration（END） in patients with acute large artery atherosclerotic（LAA） stroke. Methods: Patients with acute LAA stroke admitted at the Department of Neurology, Shidong Hospital of Yangpu District in Shanghai from January 2016 to December 2018 were enrolled. Serum levels of LGMN and other related laboratory indices were tested in the patients. END was defined as an increase of at least 2 points in repeated National Institutes of Health Stroke Scale (NIHSS) score within the first 72 h of hospitalization. According to whether the patients had END or not, they were divided into END group and non-END group. Multivariable logistic regression model was used to detect the independent risk factors for END. Receiver operator characteristic (ROC) curve was used to analyze the value of LGMN in predicting the occurrence of END. Results: A total of 334 patients were included, and 78 patients (23.4%) had END (END group), while the other 256 patients were of the non-END group. Univariate analysis showed that the incidence of accompanied disease (hypertension, diabetes, hyperlipidemia), vulnerable plaque formation, systolic blood pressure on admission, level of LGMN, fasting blood glucose, glycated hemoglobin, hypersensitive C-reactive protein, NIHSS score on admission in END group were statistically higher than those in non-END group (all P<0.05). The serum LGMN level was significantly lower in moderate (7.05 μg/L) and occlusion (6.80 μg/L) groups than in severe stenosis group (8.66 μg/L) (P<0.05). Multivariate logistic regression analysis showed that increased level of LGMN (OR=1.309,95% CI 1.188-1.441,P<0.001) was the independent risk factors for the occurring of END; other risk factors included vulnerable plaque formation, high systolic blood pressure on admission, high glycated hemoglobin and NIHSS score on admission. ROC curve analysis showed that the area under the curve of LGMN for predicting END was 0.715 (95% CI: 0.663-0.763, P<0.001), with an optimal cut-off value of 6.73 μg/L. Conclusions: Increased level of LGMN is an independent risk factor for END in patients with LAA stroke, which may be used as a biomarker for predicting END in patients with the disease.

Key words: Stroke, Legumain, Early neurological deterioration

中图分类号:

R541.7

戎天艺, 花芸, 陈德艳, 何旻. 血清天冬酰胺内肽酶与急性大动脉粥样硬化型卒中间相关性的前瞻性研究[J]. 诊断学理论与实践, 2021, 20(02): 184-189.

RONG Tianyi, HUA Yun, CHEN Deyan, HE Min. Prospective study on relationship between legumain and early neurological deterioration in patients with acute large artery atherosclerotic stroke[J]. Journal of Diagnostics Concepts & Practice, 2021, 20(02): 184-189.

图/表 5

图1

表1

END组与非END组资料比较

变量	非END组（n=256）	END组（n=78）	t值,或 χ²值,或Z值	P值
年龄（岁）（$\bar{x}±s$）	71.2±10.8	72.8±9.7	-1.221	0.224
男性[n(%）]	159(62.1)	45(57.7)	0.491	0.484
体质量指数（kg/m²）（$\bar{x}±s$）	23.4±3.6	24.1±2.9	-1.430	0.154
血管危险因素[n（%）]
高血压	183（71.5）	67（85.9）	6.597	0.010
糖尿病	109（42.6）	46（59.0）	6.462	0.011
心房颤动	36（14.1）	9（11.5）	0.327	0.568
高血脂	94（36.7）	41（52.6）	6.233	0.013
目前吸烟	87（34.0）	26（33.3）	0.011	0.915
目前喝酒	49（19.1）	19（24.4）	1.004	0.316
易损斑块	186（72.7）	66（84.6）	4.616	0.032
颅内血管狭窄程度[n（%）]			5.755	0.056
中度	102（39.8）	21（26.9）
重度	84（33.0）	26（33.3）
闭塞	70（27.3）	31（39.7）
血压（mmHg）（$\bar{x}±s$）
入院收缩压	138.4±16.7	144.9±20.9	-2.800	0.005
入院舒张压	81.0±9.9	83.1±11.1	-1.557	0.120
LGMN（μg/L）[M（IQR）]	5.11(4.45, 6.56)	7.41(5.28,9.04)	-5.750	<0.001
空腹血糖（mmol/L）[M（IQR）]	5.49(4.87, 7.02)	6.00（5.21,8.55）	-2.385	0.017
超敏C反应蛋白（mg/L）[M（IQR）]	2.45(1.00,5.40)	4.2(1.50,6.23)	-2.513	0.012
国际标准化比值（$\bar{x}±s$）	0.94±0.10	0.95±0.08	0.058	0.954
D-二聚体（mg/L）（$\bar{x}±s$）	0.37(0.23,0.70)	0.50(0.21,0.97)	-0.843	0.399
胆固醇（mmol/L）（$\bar{x}±s$）	4.61±1.13	4.76±1.16	-1.050	0.295
甘油三酯（mmol/L）（$\bar{x}±s$）	1.57±1.60	1.57±0.95	0.002	0.999
高密度脂蛋白胆固醇（mmol/L）（$\bar{x}±s$）	1.16±0.26	1.20±0.29	-1.128	0.260
低密度脂蛋白胆固醇（mmol/L）（$\bar{x}±s$）	2.78±0.85	2.62±1.14	1.127	0.262
糖化血红蛋白（%）（$\bar{x}±s$）	6.89±1.63	7.44±2.20	-2.033	0.045
卒中部位[n(%）]			1.762	0.184
前循环	156（60.9）	54（69.2）
后循环	100（39.1）	24（30.8）
入院NIHSS评分（分）[M（IQR）]	4(2,6)	5(3,8)	-4.084	<0.001
他汀类药物[n(%）]	52（20.3）	16（20.5）	0.001	0.969

表1

表2

图2

表3

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变量	回归系数	标准误	Wald	OR值(95%CI)	P值
易损斑块	0.892	0.380	5.500	2.441(1.158~5.144)	0.019
入院收缩压	0.020	0.008	6.123	1.020(1.004~1.035)	0.013
LGMN	0.269	0.049	29.934	1.309(1.188~1.441)	<0.001
糖化血红蛋白	0.179	0.074	5.808	1.196(1.034~1.384)	0.016
入院NIHSS评分	0.064	0.025	6.243	1.066(1.014~1.120)	0.012

变量	中度狭窄组组（n=21）	重度狭窄组（n=26）	闭塞组（n=31）	P值
LGMN（μg/L）[M（IQR）]	7.05(4.71, 7.95)^a)	8.66(7.46,11.28)	6.80(4.87,7.82)^a)	0.004
空腹血糖（mmol/L）[M（IQR）]	5.97(4.81, 8.18)	6.09（5.36,8.74）	6.00(5.25,9.45)	0.630
超敏C反应蛋白（mg/L）[M（IQR）]	2.30(1.40, 4.70)	4.00（1.73,6.53）	4.30(1.80, 7.70)	0.354
国际标准化比值（$\bar{x}±s$）	0.94±0.09	0.95±0.06	0.95±0.08	0.987
D-二聚体（mg/L）（$\bar{x}±s$）	0.40（0.19, 0.99）	0.47（0.20,0.60）	0.53（0.21,1.69）	0.441
胆固醇（mmol/L）（$\bar{x}±s$）	5.08±1.13	4.72±1.13	4.57±1.19	0.300
甘油三酯（mmol/L）($\bar{x}±s$）	1.72±0.78	1.38±0.51	1.63±1.28	0.422
高密度脂蛋白胆固醇（mmol/L）($\bar{x}±s$）	1.25±0.34	1.20±0.26	1.20±0.29	0.568
低密度脂蛋白胆固醇（mmol/L）($\bar{x}±s$）	2.98±1.29	2.35±1.26	2.60±0.86	0.173
糖化血红蛋白（%）（$\bar{x}±s$）	6.90±1.66	7.45±1.81	7.79±2.75	0.367