急性缺血性卒中人群血清同型半胱氨酸水平临床特点

doi:10.3969/j.issn.1004-583X.2021.11.006

摘要/Abstract

摘要：

目的回顾性分析急性缺血性脑卒中人群中血清同型半胱氨酸(HCY)水平的临床特点,探讨HCY升高相关的危险因素,为急性缺血性脑卒中的二级预防提供参考。方法回顾性收集我院2019年1月-2019年12月经头颅MRI中DWI和ADC序列确诊为急性缺血性脑卒中的患者1 055例,收集一般临床资料及HCY水平,以性别和年龄进行分层分析。采用t检验或单因素方差方法比较组间指标有无统计学差异,采用二元逻辑回归方法分析HCY的相关危险因素。结果 1 055例急性缺血性脑卒中患者年龄28~98岁,平均(66.4±11.7)岁。HCY水平为3.7~115.5 μmol/L,平均(20.1±13.0) μmol/L。按性别分层的分析结果显示,女性年龄显著大于男性,而其HCY水平显著低于男性(均P<0.05)。按性别和年龄分层后的分析结果显示,在男性中不同年龄组间HCY水平无显著差异(P>0.05),在女性中不同年龄组间HCY水平不等,年龄>80岁人群HCY水平显著高于年龄<50岁及7180岁人群(均P<0.05)。二元逻辑回归分析结果显示,男性、年龄及2型糖尿病是HCY水平的独立危险因素。结论急性缺血性脑卒中人群中男性、高龄和2型糖尿病患者HCY水平较高,在这类人群的二级预防中降低HCY水平可能使患者获益更大。

关键词: 卒中, 脑缺血, 高半胱氨酸, 危险因素

Abstract:

Objective To retrospectively analyze the clinical characteristics of serum homocysteine(HCY) in patients with acute ischemic stroke(AIS) for the risk factors associated with increased HCY in AIS secondary prevention. Methods A restrespective study was performed in 1 055 patients diagnozed AIS by diffusion weighted imaging(DWI) and apparent diffusion coefficient(ADC) sequence of cranial MRI in our hospital from January 2019 to December 2019. General informations and HCY levels were based on gender and age. The T test or one-way analysis of variance(ANOVA) method was used to compare the difference between groups and binary Logistic regression method was used to analyze the risk factors for HCY. Results The age range for 1 055 AIS patients was 28 to 98 years, (66.4±11.7) years, HCY 3.7-115.5 μmol/L, (20.1±13.0) μmol/L. The stratified analysis based on gender showed that the age of female was significantly increased when comparing with males, while HCY of female was significantly decreased (all P<0.05). The stratified analysis based on the combination of gender and age showed the difference was not statistically significant in HCY level in males in different age groups (P>0.05). HCY level in females were different and HCY of patients aged over 80 years was significantly increased than aged under 50 years and aged 71-80 years (all P<0.05). Binary logistic regression analysis showed that the independent risk factors for HCY were male, age, and type 2 diabetes mellitus. Conclusion Higher HCY are noted in male, elderly, T2DM of AIS patients, the reduction of HCY may allow the patients to obtain greater benefits in the secondary prevention.

Key words: stroke, brain ischemia, homocysteine, risk factors

中图分类号:

R743

周海涛, 黄超, 王浩, 刘瑞华, 杜艳姣, 任向阳. 急性缺血性卒中人群血清同型半胱氨酸水平临床特点[J]. 临床荟萃, 2021, 36(11): 991-995.

Zhou Haitao, Huang Chao, Wang Hao, Liu Ruihua, Du Yanjiao, Ren Xiangyang. Clinical analysis of serum homocysteine in patients with acute ischemic stroke[J]. Clinical Focus, 2021, 36(11): 991-995.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.11.006

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I11/991

图/表 5

参考文献 37

[1]	彭斌, 吴波. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志, 2018, 51(9):666-682.
[2]	中华医学会神经病学分会脑血管病学组“卒中一级预防指南”撰写组. 中国卒中一级预防指南2010[J]. 中华神经科杂志, 2011, 4(44):282-288.
[3]	沈珺, 吴丹红, 黄菲菲, 等. 急性脑卒中患者血清溶血磷脂酸和同型半胱氨酸水平变化及其与预后的关系[J]. 疑难病杂志, 2016, 15(10):1016-1019.
[4]	Wu X, Zhang L, Miao Y, et al. Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis[J]. Redox Biol, 2019, 20:46-59. doi: 10.1016/j.redox.2018.09.021 URL
[5]	Djuric D, Jakovljevic V, Zivkovic V, et al. Homocysteine and homocysteine-related compounds: An overview of the roles in the pathology of the cardiovascular and nervous systems[J]. Can J Physiol Pharmacol, 2018, 96(10):991-1003. doi: 10.1139/cjpp-2018-0112 URL
[6]	Hankey GJ, Eikelboom JW. Homocysteine and stroke[J]. Curr Opin Neurol, 2001, 14(1):95-102. pmid: 11176224
[7]	Spence JD. Nutrition and risk of stroke[J]. Nutrients, 2019, 11(3):647. doi: 10.3390/nu11030647 URL
[8]	Larsson SC, Traylor M, Markus HS. Homocysteine and small vessel stroke: A mendelian randomization analysis[J]. Ann Neurol, 2019, 85(4):495-501. doi: 10.1002/ana.v85.4 URL
[9]	Spence JD. Homocysteine lowering for stroke prevention: Unravelling the complexity of the evidence[J]. Int J Stroke, 2016, 11(7):744-747. doi: 10.1177/1747493016662038 pmid: 27462097
[10]	Zhao M, Wang X, He M, et al. Homocysteine and stroke risk: Modifying effect of methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention[J]. Stroke, 2017, 48(5):1183-1190. doi: 10.1161/STROKEAHA.116.015324 pmid: 28360116
[11]	Zhou H, Huang C, Liu R, et al. Lack of association between serum homocysteine level and middle cerebral artery stenosis[J]. Brain Behav, 2019, 9(8):e01297.
[12]	Jiang S, Xu W, Chen Z, et al. Hydrogen sulphide reduces hyperhomocysteinaemia-induced endothelial ER stress by sulfhydrating protein disulphide isomerase to attenuate atherosclerosis[J]. J Cell Mol Med, 2021, 25(7):3437-3448. doi: 10.1111/jcmm.16423 pmid: 33675119
[13]	Paganelli F, Mottola G, Fromonot J, et al. Hyperhomocysteinemia and cardiovascular disease: Is the adenosinergic system the missing link?[J]. Int J Mol Sci, 2021, 22(4):1690. doi: 10.3390/ijms22041690 URL
[14]	Ji Y, Li X, Teng Z, et al. Homocysteine is associated with the development of cerebral small vessel disease: Retrospective analyses from neuroimaging and cognitive outcomes[J]. J Stroke Cerebrovasc Dis, 2020, 29(12):105393.
[15]	Gasecka A, Siwik D, Gajewska M, et al. Early biomarkers of neurodegenerative and neurovascular disorders in diabetes[J]. J Clin Med, 2020, 9(9):2807. doi: 10.3390/jcm9092807 URL
[16]	Spence JD, Azarpazhooh MR, Larsson SC, et al. Stroke prevention in older adults: Recent advances[J]. Stroke, 2020, 51(12):3770-3777. doi: 10.1161/STROKEAHA.120.031707 pmid: 33121384
[17]	Jakubowski H. Homocysteine modification in protein structure/function and human disease[J]. Physiol Rev, 2019, 99(1):555-604. doi: 10.1152/physrev.00003.2018 pmid: 30427275
[18]	McCully KS. Homocysteine and the pathogenesis of atherosclerosis[J]. Expert Rev Clin Pharmacol, 2015, 8(2):211-219. doi: 10.1586/17512433.2015.1010516 URL
[19]	Moll S, Varga EA. Homocysteine and MTHFR mutations[J]. Circulation, 2015, 132(1):e6-e9.
[20]	Esse R, Barroso M, de Almeida IT, et al. The contribution of homocysteine metabolism disruption to endothelial dysfunction: State-of-the-art[J]. Int J Mol Sci, 2019, 20(4):867. doi: 10.3390/ijms20040867 URL
[21]	周艺璇, 林伟钊, 李瑞满. 同型半胱氨酸与妊娠期高血压疾病相关性的meta分析[J]. 临床荟萃, 2021, 36(2):101-106.
[22]	Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: An expert opinion[J]. Clin Chem, 2004, 50(1):3-32. pmid: 14709635
[23]	Duan H, Zhang Q, Liu J, et al. Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis[J]. Pharmacol Res, 2021, 168:105599.
[24]	Ji C, Yi H, Huang J, et al. Propofol alleviates inflammation and apoptosis in HCY induced HUVECs by inhibiting endoplasmic reticulum stress[J]. Mol Med Rep, 2021, 23(5):333-342. doi: 10.3892/mmr URL
[25]	Stojan G, Li J, Liu T, et al. Intracellular homocysteine metabolites in SLE: Plasma S-adenosylhomocysteine correlates with coronary plaque burden[J]. Lupus Sci Med, 2021, 8(1):e000453.
[26]	巩涛, 高云, 胡月圆, 等. 同型半胱氨酸与急性脑梗死早期神经功能缺损严重程度及预后的关系[J]. 临床荟萃, 2021, 36(1):35-38.
[27]	Armitage JM, Bowman L, Clarke RJ, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: A randomized trial[J]. JAMA, 2010, 303(24):2486-2494. doi: 10.1001/jama.2010.840 pmid: 20571015
[28]	Carlsson CM. Homocysteine lowering with folic acid and vitamin B supplements: Effects on cardiovascular disease in older adults[J]. Drugs Aging, 2006, 23(6):491-502. doi: 10.2165/00002512-200623060-00004 URL
[29]	Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction[J]. N Engl J Med, 2006, 354(15):1578-1588. doi: 10.1056/NEJMoa055227 URL
[30]	Bhargava S, Ali A, Bhargava EK, et al. Lowering homocysteine and modifying nutritional status with folic acid and vitamin B(12) in Indian patients of vascular disease[J]. J Clin Biochem Nutr, 2012, 50(3):222-226. doi: 10.3164/jcbn.11-72 pmid: 22573925
[31]	Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease[J]. N Engl J Med, 2006, 354(15):1567-1577. doi: 10.1056/NEJMoa060900 URL
[32]	Kaye AD, Jeha GM, Pham AD, et al. Folic acid supplementation in patients with elevated homocysteine levels[J]. Adv Ther, 2020, 37(10):4149-4164. doi: 10.1007/s12325-020-01474-z URL
[33]	Wang L, Zhang Y. Role of hyperhomocysteine, thyroid dysfunction and their interaction in ischemic stroke patients with non-valvular atrial fibrillation[J]. Sci Rep, 2020, 10(1):12419. doi: 10.1038/s41598-020-69449-2 URL
[34]	Malinowska A, Chmurzynska A. Polymorphism of genes encoding homocysteine metabolism-related enzymes and risk for cardiovascular disease[J]. Nutr Res, 2009, 29(10):685-695. doi: 10.1016/j.nutres.2009.09.018 pmid: 19917447
[35]	Xiang T, Xiang H, Yan M, et al. Systemic risk factors correlated with hyperhomocysteinemia for specific MTHFR C677T genotypes and sex in the chinese population[J]. Ann Transl Med, 2020, 8(21):1455. doi: 10.21037/atm URL
[36]	Brouwer IA, van Rooij IA, van Dusseldorp M, et al. Homocysteine-lowering effect of 500 microg folic acid every other day versus 250 microg/day[J]. Ann Nutr Metab, 2000, 44(5-6):194-197. pmid: 11146323
[37]	Spence JD. Recent advances in preventing recurrent stroke[J]. F1000Res, 2020, 9: F1000 Faculty Rev-1012.

项目	数据
性别[例(%)]
男	670(63.5)
女	385(36.5)
年龄(岁)	66.4±11.7
吸烟史[例(%)]
无	669(63.4)
偶尔或戒烟	86(8.2)
经常	300(28.4)
饮酒史[例(%)]
无	915(86.7)
偶尔或戒酒	74(7.0)
经常	66(6.3)
高血压病[例(%)]	612(58.0)
2型糖尿病[例(%)]	436(41.3)
冠心病[例(%)]	218(20.7)
心房颤动[例(%)]	56(5.3)
HCY(μmol/L)	20.1±13.0
≤15.4 μmol/L[例(%)]	460(43.6)
>15.4 μmol/L[例(%)]	595(56.4)

项目	数据
性别[例(%)]
男	670(63.5)
女	385(36.5)
年龄(岁)	66.4±11.7
吸烟史[例(%)]
无	669(63.4)
偶尔或戒烟	86(8.2)
经常	300(28.4)
饮酒史[例(%)]
无	915(86.7)
偶尔或戒酒	74(7.0)
经常	66(6.3)
高血压病[例(%)]	612(58.0)
2型糖尿病[例(%)]	436(41.3)
冠心病[例(%)]	218(20.7)
心房颤动[例(%)]	56(5.3)
HCY(μmol/L)	20.1±13.0
≤15.4 μmol/L[例(%)]	460(43.6)
>15.4 μmol/L[例(%)]	595(56.4)

项目	HCY(μmol/L)			统计值	P值
项目	≤15.4 (n=460)	15.5~30.0 (n=470)	>30.0 (n=125)	统计值	P值
性别[例(%)]
男女	230(50.0) 230(50.0)	335(71.3) 135(28.7)	105(84.0) 20(16.0)	χ²=64.904	<0.05
年龄(岁)	65.3±11.1	68.1±11.6	63.8±13.0	F=10.199	<0.05
高血压病[例(%)]	266(57.8)	272(57.8)	74(59.2)	χ²=0.083	0.959
2型糖尿病[例(%)]	230(50.0)	169(36.0)	37(29.6)	χ²=26.948	<0.05
冠心病[例(%)]	101(22.0)	97(20.6)	20(16.0)	χ²=2.128	0.345
心房颤动[例(%)]	25(5.4)	26(5.5)	5(4.0)	χ²=0.487	0.784

项目	HCY(μmol/L)			统计值	P值
项目	≤15.4 (n=460)	15.5~30.0 (n=470)	>30.0 (n=125)	统计值	P值
性别[例(%)]
男女	230(50.0) 230(50.0)	335(71.3) 135(28.7)	105(84.0) 20(16.0)	χ²=64.904	<0.05
年龄(岁)	65.3±11.1	68.1±11.6	63.8±13.0	F=10.199	<0.05
高血压病[例(%)]	266(57.8)	272(57.8)	74(59.2)	χ²=0.083	0.959
2型糖尿病[例(%)]	230(50.0)	169(36.0)	37(29.6)	χ²=26.948	<0.05
冠心病[例(%)]	101(22.0)	97(20.6)	20(16.0)	χ²=2.128	0.345
心房颤动[例(%)]	25(5.4)	26(5.5)	5(4.0)	χ²=0.487	0.784

性别	例数	年龄 (岁)	HCY (μmol/L)	高血压病 [例(%)]	2型糖尿病 [例(%)]	冠心病 [例(%)]	心房颤动 [例(%)]
男	670	64.9±11.9	22.4±14.8	380(56.7)	277(41.3)	125(18.7)	35(5.2)
女	385	69.1±10.8	16.2±7.7	232(60.3)	159(41.3)	93(24.2)	21(5.5)
统计值		t=-5.949	t=8.898	χ²=1.260	χ²=0	χ²=4.510	χ²=0.026
P值		<0.05	<0.05	0.262	0.989	<0.05	0.872