血清25-羟维生素D水平与急性缺血性脑卒中患者炎性反应及短期预后的关系研究
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摘要
背景目前,有关25-羟维生素D〔25-(OH)D〕缺乏与急性缺血性脑卒中(AIS)患者预后关系的研究结果不一致,而其与AIS患者炎性反应关系的研究报道较少见。目的探讨血清25-(OH)D水平与AIS患者炎性反应及短期预后的关系。方法选取2016年1月—2018年10月辽阳市中心医院神经内科收治的AIS患者198例,根据血清25-(OH)D水平分为正常组〔25-(OH)D≥30μg/L,n=86〕、不足组〔25-(OH)D为20～29μg/L,n=67〕及缺乏组〔25-(OH)D<20μg/L,n=45〕。比较3组患者炎性反应指标〔包括白细胞计数(WBC)、红细胞沉降率(ESR)及血清降钙素原(PCT)、超敏C反应蛋白(hs-CRP)、白介素6(IL-6)、白介素10(IL-10)水平〕,入院时及出院时美国国立卫生研究院卒中量表(NIHSS)评分,入院时、出院时及出院后3个月改良Rankin量表(mRS)评分;血清25-(OH)D水平与AIS患者炎性反应指标的相关性分析采用多元线性回归分析,血清25-(OH)D水平与AIS患者mRS评分的相关性分析采用Spearman秩相关分析,AIS患者短期预后的影响因素分析采用多因素Logistic回归分析。结果 (1)3组患者血清PCT、IL-10水平比较,差异无统计学意义(P>0.05)。不足组和缺乏组患者WBC低于正常组,ESR快于正常组,血清hs-CRP、IL-6水平高于正常组(P<0.05);缺乏组患者WBC低于不足组,ESR快于不足组,血清hs-CRP、IL-6水平高于不足组(P<0.05)。多元线性回归分析结果显示,血清25-(OH)D水平与AIS患者血清hs-CRP、IL-6水平呈负相关(β值分别为-0.090、-0.074,P<0.05)。(2)3组患者入院时NIHSS评分、m RS评分及出院时NIHSS评分比较,差异无统计学意义(P>0.05);出院时及出院后3个月,不足组和缺乏组患者m RS评分高于正常组,缺乏组患者m RS评分高于不足组(P<0.05)。Spearman秩相关分析结果显示,血清25-(OH)D水平与AIS患者出院时及出院后3个月mRS评分呈负相关(r值分别为-0.467、-0.527,P<0.01)。(3)多因素Logistic回归分析结果显示,25-(OH)D缺乏是AIS患者短期预后的独立影响因素〔OR=3.162,95%CI(1.347,7.424),P<0.05〕。结论 25-(OH)D不足/缺乏与AIS患者炎性反应加重及短期预后不良有关,且25-(OH)D缺乏是AIS患者短期预后的独立影响因素。
Background Research results about relationship between lack of 25-(OH)D and acute ischemic stroke(AIS)is conflicting at present,while research about relationship between lack of 25-(OH)D and inflammatory reaction in patients with acute ischemic stroke is relatively rare. Objective To investigate the relationship between serum 25-(OH)D level and inflammatory reaction,short-term prognosis in patients with AIS. Methods From January 2016 to October2018,a total of 198 patients with AIS were selected in the Department of Neurology,the Central Hospital of Liaoyang,and they were divided into normal group〔with serum 25-(OH)D level ≥ 30 μg/L,n=86〕,insufficient group〔with serum 25-(OH)D level between 20 and 29 μg/L,n=67〕and lacking group〔with serum 25-(OH)D level<20 μg/L,n=45〕according to the serum 25-(OH)D level. Inflammatory reaction indicators(including WBC,ESR,serum levels of PCT,hs-CRP,IL-6 and IL-10),NIHSS score at admission and at discharge,mRS score at admission,at discharge and 3 months after discharge were compared between the two groups;multivariate linear regression analysis was used to analyze the correlations of serum 25-(OH)D with inflammatory reaction indicators in patients with AIS,Spearman rank correlation analysis was used to analyze the correlation between serum 25-(OH)D level and mRS score in patients with AIS,multivariate Logistic regression analysis was used to analyze the influencing factors short-term prognosis in patients with AIS,respectively. Results(1)No statistically significant difference of serum level of PCT or IL-10 was found in the three groups(P>0.05).WBC in insufficient group and lacking group was statistically significantly lower than that in normal group,respectively,ESR in insufficient group and lacking group was statistically significantly faster than that in normal group,respectively,while serum levels of hs-CRP and IL-6 in insufficient group and lacking group were statistically significantly higher than those in normal group(P<0.05);WBC in lacking group was statistically significantly lower than that in insufficient group,ESR in lacking group was statistically significantly faster than that in insufficient group,while serum levels of hs-CRP and IL-6 in lacking group were statistically significantly higher than those in insufficient group(P<0.05). Multivariate linear regression analysis results showed that,serum 25-(OH)D level was negatively correlated with serum levels of hs-CRP(β=-0.090)and IL-6(β=-0.074)in patients with AIS,respectively(P<0.05).(2)No statistically significant difference of NIHSS score or mRS score at admission,or NIHSS score at discharge was found in the three groups(P>0.05);at discharge and 3 months after discharge,mRS score in insufficient group and lacking group was statistically significantly higher than that in normal group,respectively,meanwhile mRS score in lacking group was statistically significantly higher than that in insufficient group(P<0.05).Spearman rank correlation analysis results showed that,25-(OH)D level was negatively correlated with mRS score at discharge(r=-0.467)and 3 months after discharge(r=-0.527)in patients with AIS,respectively(P<0.01).(3)Multivariate Logistic regression analysis results showed that,25-(OH)D lacking was one of independent influencing factors of short-term prognosis in patients with AIS〔OR=3.162,95%CI(1.347,7.424),P<0.05〕. Conclusion Insufficiency/lacking of 25-(OH)D is significantly correlated with aggravation of inflammatory reaction and poor short-term prognosis in patients with AIS,respectively,25-(OH)D lacking is one of independent influencing factors of short-term prognosis in patients with AIS.
Background Research results about relationship between lack of 25-(OH)D and acute ischemic stroke(AIS)is conflicting at present,while research about relationship between lack of 25-(OH)D and inflammatory reaction in patients with acute ischemic stroke is relatively rare. Objective To investigate the relationship between serum 25-(OH)D level and inflammatory reaction,short-term prognosis in patients with AIS. Methods From January 2016 to October2018,a total of 198 patients with AIS were selected in the Department of Neurology,the Central Hospital of Liaoyang,and they were divided into normal group〔with serum 25-(OH)D level ≥ 30 μg/L,n=86〕,insufficient group〔with serum 25-(OH)D level between 20 and 29 μg/L,n=67〕and lacking group〔with serum 25-(OH)D level<20 μg/L,n=45〕according to the serum 25-(OH)D level. Inflammatory reaction indicators(including WBC,ESR,serum levels of PCT,hs-CRP,IL-6 and IL-10),NIHSS score at admission and at discharge,mRS score at admission,at discharge and 3 months after discharge were compared between the two groups;multivariate linear regression analysis was used to analyze the correlations of serum 25-(OH)D with inflammatory reaction indicators in patients with AIS,Spearman rank correlation analysis was used to analyze the correlation between serum 25-(OH)D level and mRS score in patients with AIS,multivariate Logistic regression analysis was used to analyze the influencing factors short-term prognosis in patients with AIS,respectively. Results(1)No statistically significant difference of serum level of PCT or IL-10 was found in the three groups(P>0.05).WBC in insufficient group and lacking group was statistically significantly lower than that in normal group,respectively,ESR in insufficient group and lacking group was statistically significantly faster than that in normal group,respectively,while serum levels of hs-CRP and IL-6 in insufficient group and lacking group were statistically significantly higher than those in normal group(P<0.05);WBC in lacking group was statistically significantly lower than that in insufficient group,ESR in lacking group was statistically significantly faster than that in insufficient group,while serum levels of hs-CRP and IL-6 in lacking group were statistically significantly higher than those in insufficient group(P<0.05). Multivariate linear regression analysis results showed that,serum 25-(OH)D level was negatively correlated with serum levels of hs-CRP(β=-0.090)and IL-6(β=-0.074)in patients with AIS,respectively(P<0.05).(2)No statistically significant difference of NIHSS score or mRS score at admission,or NIHSS score at discharge was found in the three groups(P>0.05);at discharge and 3 months after discharge,mRS score in insufficient group and lacking group was statistically significantly higher than that in normal group,respectively,meanwhile mRS score in lacking group was statistically significantly higher than that in insufficient group(P<0.05).Spearman rank correlation analysis results showed that,25-(OH)D level was negatively correlated with mRS score at discharge(r=-0.467)and 3 months after discharge(r=-0.527)in patients with AIS,respectively(P<0.01).(3)Multivariate Logistic regression analysis results showed that,25-(OH)D lacking was one of independent influencing factors of short-term prognosis in patients with AIS〔OR=3.162,95%CI(1.347,7.424),P<0.05〕. Conclusion Insufficiency/lacking of 25-(OH)D is significantly correlated with aggravation of inflammatory reaction and poor short-term prognosis in patients with AIS,respectively,25-(OH)D lacking is one of independent influencing factors of short-term prognosis in patients with AIS.
引文
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[7]SAFAIE N,REZAEE H,SEIF DVATI B,et al.Vitamin DDeficiency Predicts the ST Elevation Type of Myocardial Infarction in Patients with Acute Coronary Syndrome[J].Iran J Pharm Res,2018,17(Suppl):73-78.
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[12]陈欢,卓文燕,朱培培,等.25-羟基维生素D联合尿酸对缺血性脑卒中严重程度及早期预后的评估价值[J].中国实用神经疾病杂志,2017,20(5):3-7.DOI:10.3969/j.issn.1673-5110.2017.05.002.
[13]MAJUMDAR V,PRABHAKAR P,KULKARNI G B,et al.Vitamin D status,hypertension and ischemic stroke:a clinical perspective[J].J Hum Hypertens,2015,29(11):669-674.DOI:10.1038/jhh.2015.10.
[14]GUPTA A,PRABHAKAR S,MODI M,et al.Vitamin Dstatus and risk of ischemic stroke in North Indian patients[J].Indian J Endocrinol Metab,2014,18(5):721-725.DOI:10.4103/2230-8210.139241.
[15]杜伟杰,李威,方玲,等.尿激酶静脉溶栓治疗急性轻型缺血性脑卒中疗效观察[J].山东医药,2017,57(31):82-84.DOI:10.3969/j.issn.1002-266X.2017.31.025.
[16]徐叶,黄思思,何睿瑜,等.血清骨桥蛋白水平与急性脑出血患者病情及预后的关系[J].内科急危重症杂志,2017,23(3):189-191,200.DOI:10.11768/nkjwzzzz20170304.
[17]TAHERAGHDAM A,AMINNEJAD S,PASHAPOUR A,et al.Is there a correlation between hs-CRP levels and functional outcome of Ischemic Stroke?[J].Pak J Med Sci,2013,29(1):166-169.DOI:10.12669/pjms.291.2799.
[18]SERPERO L D,BELLISSIMA V,COLIVICCHI M,et al.Next generation biomarkers for brain injury[J].J Matern Fetal Neonatal Med,2013,26(Suppl 2):44-49.DOI:10.3109/14767058.2013.829688.
[19]YOSHIDA M,KATO N,UEMURA T,et al.Time dependent transition of the levels of protein-conjugated acrolein(PC-Acro),IL-6 and CRP in plasma during stroke[J].eNeurologicalSci,2017,7:18-24.DOI:10.1016/j.ensci.2017.03.005.
[20]TANGER?S L H,AUSTDAL M,SKR?STAD R B,et al.Distinct first trimester cytokine profiles for gestational hypertension and preeclampsia[J].Arterioscler Thromb Vasc Biol,2015,35(11):2478-2485.DOI:10.1161/ATVBAHA.115.305817.
[21]WITHAM M D,DOVE F J,SUGDEN J A,et al.The effect of vitamin D replacement on markers of vascular health in stroke patients-a randomised controlled trial[J].Nutr Metab Cardiovasc Dis,2012,22(10):864-870.DOI:10.1016/j.numecd.2010.11.001.
[22]KAJTA M,MAKAREWICZ D,ZIEMINSKANE,et al.Neuroprotection by co-treatment and post-treating with calcitriol following the ischemic and excitotoxic insult in vivo and in vitro[J].Neurochem Int,2009,55(5):265-274.DOI:10.1016/j.neuint.2009.03.010.
[23]朱梅生,周晓辉,马燕.新疆维吾尔族和汉族轻度认知功能障碍患者25羟维生素D水平研究[J].中华老年医学杂志,2017,36(3):321-324.DOI:10.3760/cma.j.issn.0254-9026.2017.03.023.
[24]PARK K Y,CHUNG P W,KIM Y B,et al.Serum vitamin Dstatus as a predictor of prognosis in patients with acute ischemic stroke[J].Cerebrovasc Dis,2015,40(1/2):73-80.DOI:10.1159/000434691.
[25]徐樱溪,赵晴,孙灿,等.维生素D受体对内毒素感染小鼠肺组织肾素-血管紧张素系统的影响[J].实用药物与临床,2017,20(5):487-491.DOI:10.14053/j.cnki.ppcr.201705001.
[26]潘伟男,邓水秀.维生素D受体及维生素D受体激动剂的研究进展[J].广州医药,2014,45(6):83-86.DOI:10.3969/j.issn.1000-8535.2014.06.031.
[27]SCHNEIDER A L,LUTSEY P L,SELVIN E,et al.Vitamin D,vitamin D binding protein gene polymorphisms,race and risk of incident stroke:the Atherosclerosis Risk in Communities(ARIC)study[J].Eur J Neurol,2015,22(8):1220-1227.DOI:10.1111/ene.12731.
[28]ZHANG B,WANG Y,ZHONG Y,et al.Serum 25-hydroxyvitamin D deficiency predicts poor outcome among acute ischemic stroke patients without hypertension[J].Neurochem Int,2018,118:91-95.DOI:10.1016/j.neuint.2018.05.001.
[29]KALUEFF A V,TUOHIMAA P.Neurosteroid hormone vitamin D and its utility in clinical nutrition[J].Curr Opin Clin Nutr Metab Care,2007,10(1):12-19.DOI:10.1097/MCO.0b013e328010ca18.
[2]WANG Z Y,SUN Z R,ZHANG L M.The relationship between serum mannose-binding lectin levels and acute ischemic stroke risk[J].Neurochem Res,2014,39(2):248-253.DOI:10.1007/s11064-013-1214-x.
[3]Writing Group Members,MOZAFFARIAN D,BENJAMIN E J,et al.Heart Disease and Stroke Statistics-2016 Update:A Report From the American Heart Association[J].Circulation,2016,133(4):e38-360.DOI:10.1161/CIR.0000000000000350.
[4]HILGER J,FRIEDEL A,HERR R,et al.A systematic review of vitamin D status in populations worldwide[J].Br J Nutr,2014,111(1):23-45.DOI:10.1017/S0007114513001840.
[5]MILAZZO V,DE METRIO M,COSENTINO N,et al.Vitamin D and acute myocardial infarction[J].WJC,2017,9(1):14.DOI:10.4330/wjc.v9.i1.14.
[6]MIRHOSSEINI N,RAINSBURY J,KIMBALL S M.Vitamin D supplementation,serum 25(OH)D concentrations and cardiovascular disease risk factors:A systematic review and metaanalysis[J].Front Cardiovasc Med,2018,5:87.DOI:10.3389/fcvm.2018.00087.
[7]SAFAIE N,REZAEE H,SEIF DVATI B,et al.Vitamin DDeficiency Predicts the ST Elevation Type of Myocardial Infarction in Patients with Acute Coronary Syndrome[J].Iran J Pharm Res,2018,17(Suppl):73-78.
[8]SUN Q,PAN A,HU F B,et al.25-Hydroxyvitamin D levels and the risk of stroke:a prospective study and meta-analysis[J].Stroke,2012,43(6):1470-1477.DOI:10.1161/STROKEAHA.111.636910.
[9]TU W J,ZHAO S J,XU D J,et al.Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischaemic stroke[J].Clin Sci(Lond),2014,126(5):339-346.DOI:10.1042/CS20130284.
[10]BR?NDUM-JACOBSEN P,NORDESTGAARD B G,SCHNOHRP,et al.25-hydroxyvitamin D and symptomatic ischemic stroke:an original study and meta-analysis[J].Ann Neurol,2013,73(1):38-47.DOI:10.1002/ana.23738.
[11]XU T,ZHONG C,XU T,et al.Serum 25-hydroxyvitamin Ddeficiency predicts long-term poor prognosis among ischemic stroke patients without hyperglycaemia[J].Clin Chim Acta,2017,471:81-85.DOI:10.1016/j.cca.2017.05.020.
[12]陈欢,卓文燕,朱培培,等.25-羟基维生素D联合尿酸对缺血性脑卒中严重程度及早期预后的评估价值[J].中国实用神经疾病杂志,2017,20(5):3-7.DOI:10.3969/j.issn.1673-5110.2017.05.002.
[13]MAJUMDAR V,PRABHAKAR P,KULKARNI G B,et al.Vitamin D status,hypertension and ischemic stroke:a clinical perspective[J].J Hum Hypertens,2015,29(11):669-674.DOI:10.1038/jhh.2015.10.
[14]GUPTA A,PRABHAKAR S,MODI M,et al.Vitamin Dstatus and risk of ischemic stroke in North Indian patients[J].Indian J Endocrinol Metab,2014,18(5):721-725.DOI:10.4103/2230-8210.139241.
[15]杜伟杰,李威,方玲,等.尿激酶静脉溶栓治疗急性轻型缺血性脑卒中疗效观察[J].山东医药,2017,57(31):82-84.DOI:10.3969/j.issn.1002-266X.2017.31.025.
[16]徐叶,黄思思,何睿瑜,等.血清骨桥蛋白水平与急性脑出血患者病情及预后的关系[J].内科急危重症杂志,2017,23(3):189-191,200.DOI:10.11768/nkjwzzzz20170304.
[17]TAHERAGHDAM A,AMINNEJAD S,PASHAPOUR A,et al.Is there a correlation between hs-CRP levels and functional outcome of Ischemic Stroke?[J].Pak J Med Sci,2013,29(1):166-169.DOI:10.12669/pjms.291.2799.
[18]SERPERO L D,BELLISSIMA V,COLIVICCHI M,et al.Next generation biomarkers for brain injury[J].J Matern Fetal Neonatal Med,2013,26(Suppl 2):44-49.DOI:10.3109/14767058.2013.829688.
[19]YOSHIDA M,KATO N,UEMURA T,et al.Time dependent transition of the levels of protein-conjugated acrolein(PC-Acro),IL-6 and CRP in plasma during stroke[J].eNeurologicalSci,2017,7:18-24.DOI:10.1016/j.ensci.2017.03.005.
[20]TANGER?S L H,AUSTDAL M,SKR?STAD R B,et al.Distinct first trimester cytokine profiles for gestational hypertension and preeclampsia[J].Arterioscler Thromb Vasc Biol,2015,35(11):2478-2485.DOI:10.1161/ATVBAHA.115.305817.
[21]WITHAM M D,DOVE F J,SUGDEN J A,et al.The effect of vitamin D replacement on markers of vascular health in stroke patients-a randomised controlled trial[J].Nutr Metab Cardiovasc Dis,2012,22(10):864-870.DOI:10.1016/j.numecd.2010.11.001.
[22]KAJTA M,MAKAREWICZ D,ZIEMINSKANE,et al.Neuroprotection by co-treatment and post-treating with calcitriol following the ischemic and excitotoxic insult in vivo and in vitro[J].Neurochem Int,2009,55(5):265-274.DOI:10.1016/j.neuint.2009.03.010.
[23]朱梅生,周晓辉,马燕.新疆维吾尔族和汉族轻度认知功能障碍患者25羟维生素D水平研究[J].中华老年医学杂志,2017,36(3):321-324.DOI:10.3760/cma.j.issn.0254-9026.2017.03.023.
[24]PARK K Y,CHUNG P W,KIM Y B,et al.Serum vitamin Dstatus as a predictor of prognosis in patients with acute ischemic stroke[J].Cerebrovasc Dis,2015,40(1/2):73-80.DOI:10.1159/000434691.
[25]徐樱溪,赵晴,孙灿,等.维生素D受体对内毒素感染小鼠肺组织肾素-血管紧张素系统的影响[J].实用药物与临床,2017,20(5):487-491.DOI:10.14053/j.cnki.ppcr.201705001.
[26]潘伟男,邓水秀.维生素D受体及维生素D受体激动剂的研究进展[J].广州医药,2014,45(6):83-86.DOI:10.3969/j.issn.1000-8535.2014.06.031.
[27]SCHNEIDER A L,LUTSEY P L,SELVIN E,et al.Vitamin D,vitamin D binding protein gene polymorphisms,race and risk of incident stroke:the Atherosclerosis Risk in Communities(ARIC)study[J].Eur J Neurol,2015,22(8):1220-1227.DOI:10.1111/ene.12731.
[28]ZHANG B,WANG Y,ZHONG Y,et al.Serum 25-hydroxyvitamin D deficiency predicts poor outcome among acute ischemic stroke patients without hypertension[J].Neurochem Int,2018,118:91-95.DOI:10.1016/j.neuint.2018.05.001.
[29]KALUEFF A V,TUOHIMAA P.Neurosteroid hormone vitamin D and its utility in clinical nutrition[J].Curr Opin Clin Nutr Metab Care,2007,10(1):12-19.DOI:10.1097/MCO.0b013e328010ca18.