同型半胱氨酸与脑卒中患者神经功能缺损及脑血管狭窄的相关性研究

doi:10.3760/cma.j.issn.1007-1245.2022.08.025

摘要/Abstract

摘要： 目的　本文旨在探讨血同型半胱氨酸（Hcy）浓度与急性脑卒中患者入院时神经功能缺损严重程度的相关性，研究其与颅内外大动脉狭窄支数的关系。方法　纳入寿光市人民医院96例急性大动脉粥样硬化（LAA）型（颈内动脉或大脑中动脉供血区）脑卒中患者（LAA组），取同时期57例健康查体者作为对照组。采用美国国立卫生研究院卒中量表（NIHSS）对LAA组进行评分，分为NIHSS评分≥6分和NIHSS评分<6分两组。按照颅内外动脉狭窄情况将LAA组区分成3组：单支狭窄组、双支狭窄组及多支狭窄组。计量资料若符合正态分布两组间比较采用独立样本t检验，3组间比较采用单因素方差分析，若不符合正态分布则采用非参数检验；计数资料采用χ²检验。应用logistic回归分析寻找危险因素，采用受试者工作特征曲线（ROC）评估Hcy浓度预测急性脑卒中患者入院时神经功能缺损严重程度的应用价值。结果　LAA组男58例、女38例，年龄（66.38±10.93）岁；对照组男27例、女30例，年龄（61.84±10.99）岁。LAA组血浆Hcy浓度较对照组明显升高［（28.65±16.49）μmol/L比（14.56±10.47）μmol/L］（P<0.05）。NIHSS评分≥6分组血浆Hcy水平显著高于NIHSS评分<6分组［（36.63±14.00）μmol/L比（24.27±16.20）μmol/L］（P<0.05）。Hcy评价急性脑卒中患者入院时神经缺损程度的曲线下面积（AUC）为0.776（95%CI 0.683～0.868），最佳诊断值为21.43 μmol/L（灵敏度91.2%，特异度56.5%）。多支狭窄组Hcy浓度依次高于双支狭窄组、单支狭窄组［（43.25±17.40）μmol/L比（25.53±12.47）μmol/L比（18.47±7.88）μmol/L］，差异有统计学意义（P<0.05）。急性LAA型脑卒中颅内外大血管狭窄数目越多，血Hcy浓度越高。结论　Hcy水平与急性脑卒中患者入院时神经功能缺损严重程度相关。脑卒中患者颅内外大动脉狭窄支数越多，血Hcy浓度越高。Hcy为评估急性脑卒中患者入院时神经功能缺损及大动脉硬化狭窄广泛程度提供新的生物学证据。

关键词: 脑卒中, 同型半胱氨酸, 动脉粥样硬化性狭窄, 神经功能缺损

Abstract:

Objective　This study aimed to investigate how plasma homocysteine (Hcy) correlated to stroke severity in patients with large artery atherosclerosis and to evaluate the association between Hcy level and extra- and intra-cranial arterial stenosis. Methods　We enrolled 96 patients with large artery atherosclerosis (LAA) stroke (internal carotid artery and middle cerebral artery supply area) and 57 healthy controls in Shouguang People's Hospital. The LAA stroke patients were divided into two subgroups according to National Institutes of Health Stroke Scale (NIHSS): one group with NIHSS score ≥6 and another group with NIHSS score <6. Based on the intracranial and extracranial artery stenosis, the LAA stroke patients were classified into three groups: a single-vessel group, a double-vessel group, and a multi-vessel lesion group. Independent sample t test was used for comparison between two groups if the measurement data met the normal distribution, one-way ANOVA was used for comparison among three groups, and non-parametric test was used for comparison if the measurement data did not meet the normal distribution. χ² test was used for the count data. Logistic regression analysis was used to find risk factors, and receiver operating characteristic curve (ROC) was used to evaluate the application value of Hcy concentration in predicting the severity of neurological impairment in patients with acute stroke at admission. Results　There were 58 males and 38 females in the LAA group, aged (66.38±10.93) years; there were 27 males and 30 females in the control group, aged (61.84±10.99) years. The plasma Hcy concentration in the LAA group was significantly higher than that in the control group [(28.65±16.49) μmol/L vs. (14.56±10.47) μmol/L] (P<0.05). The plasma Hcy level in the NIHSS score ≥6 group was significantly higher than that in the NIHSS score <6 group [(36.63±14.00) μmol/L vs. (24.27±16.20) μmol/L] (P<0.05). The area under the curve (AUC) of Hcy for evaluating the degree of nerve defect in acute stroke patients at admission was 0.776 (95%CI 0.683-0.868), and the optimal diagnostic value was 21.43 μmol/L (a sensitivity of 91.2% and a specificity of 56.5%). The Hcy concentration in the multi-vessel stenosis group was higher than those in the double-vessel stenosis group and the single-vessel stenosis group successively [(43.25±17.40) μmol/L vs. (25.53±12.47) μmol/L vs. (18.47±7.88) μmol/L], with a statistically significant difference (P<0.05). The higher the number of intracranial and extracranial large vessel stenosis in acute LAA stroke was, the higher the plasma Hcy concentration was. Conclusions　Plasma Hcy concentration is correlated with the neurological deficit severity in stroke patients. The more intracranial and extracranial arterial stenosis the stroke patients have, the higher the plasma Hcy concentration is. Hcy may be an indicator for evaluating the neurological deficit severity and the extent of arterial stenosis in LAA stroke patients.

Key words: Stroke, Homocysteine, Atherosclerotic stenosis, Neurological deficit

杨英亮, 徐英智, 刘桂艳, 王泉亮.

同型半胱氨酸与脑卒中患者神经功能缺损及脑血管狭窄的相关性研究 [J]. 国际医药卫生导报, 2022, 28(8): 1142-1146.

Yang Yingliang, Xu Yingzhi, Liu Guiyan, Wang Quanliang. Associations between homocysteine and stroke severity and extracranial and intracranial arteriostenosis in stroke patients [J]. International Medicine and Health Guidance News, 2022, 28(8): 1142-1146.

参考文献

[1] Zhao D, Liu J, Wang W, et al. Epidemiological transition of stroke in China: twenty-one-year observational study from the Sino-MONICA-Beijing Project[J]. Stroke, 2008, 39(6):1668-1674. DOI: 10.1161/STROKEAHA.107. 502807.

[2] Sacco RL, Anand K, Lee HS, et al. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study[J]. Stroke, 2004, 35(10):2263-2269. DOI: 10.1161/01.STR.0000142374.33919.92.

[3] Wang H, Fan D, Zhang H, et al. Serum level of homocysteine is correlated to carotid artery atherosclerosis in Chinese with ischemic stroke[J]. Neurol Res, 2006, 28(1):25-30. DOI: 10.1179/016164106X91834.

[4] Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment[J]. Stroke, 1993, 24(1):35-41. DOI: 10.1161/01.str.24.1.35.

[5] Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease[J]. Annu Rev Nutr, 1992, 12:279-298. DOI: 10.1146/annurev.nu.12.070192.001431.

[6] Rawashdeh SI, Al-Mistarehi AH, Yassin A, et al. A concurrent ischemic stroke, myocardial infarction, and aortic thrombi in a young patient with hyperhomocysteinemia: a case report[J]. Int Med Case Rep J, 2020, 13:581-590. DOI: 10.2147/IMCRJ.S279603.

[7] Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis[J]. BMJ, 2002, 325(7374):1202. DOI: 10.1136/bmj.325.7374.1202.

[8] Zhang W, Zhang X. Correlation between the youth cerebral infarction in different TOAST classifications and high homocysteine[J]. Cell Biochem Biophys, 2015, 71(1):39-42. DOI: 10.1007/s12013-014-0159-2.

[9] Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine[J]. J Clin Invest, 1986, 77(4):1370-1376. DOI: 10.1172/JCI112442.

[10] Mansoor MA, Bergmark C, Svardal AM, et al. Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Homocysteine and peripheral vascular disease[J]. Arterioscler Thromb Vasc Biol, 1995, 15(2):232-240. DOI: 10.1161/01.atv.15.2.232.

[11] Thambyrajah J, Townend JN. Homocysteine and atherothrombosis--mechanisms for injury[J]. Eur Heart J, 2000, 21(12):967-974. DOI: 10.1053/euhj.1999.1914.

[12] 王桂红,王拥军,何耀,等.血浆同型半胱氨酸水平与脑大动脉粥样硬化性病变的相关性分析[J].中华内科杂志,2006,45(9):744-747. DOI:10.3760/j.issn:0578-1426. 2006. 09.013.

[13] Alsulaimani S, Gardener H, Elkind MS, et al. Elevated homocysteine and carotid plaque area and densitometry in the Northern Manhattan Study[J]. Stroke, 2013, 44(2):457-461. DOI: 10.1161/STROKEAHA.112.676155.

[14] Wu W, Guan Y, Xu K, et al. Plasma homocysteine levels predict the risk of acute cerebral infarction in patients with carotid artery lesions[J]. Mol Neurobiol, 2016, 53(4):2510-2517. DOI: 10.1007/s12035-015-9226-y.