缺血性脑卒中早期血浆和肽素水平对远期预后的影响
摘要
背景：在我国脑卒中是导致居民死亡的第一大原因，也是导致严重并发症的主要原因。大约有15%~30%的脑卒中患者永久丧失劳动力。已有报道显示急性缺血性脑卒中伴有下丘脑-垂体-肾上腺轴失衡引起内分泌功能紊乱是脑缺血第一个可测量的生理反应。研究发现，和肽素水平与缺血性脑卒中、脑出血、脑外伤、短暂性脑缺血发作患者的远期预后和/或严重程度相关，因此有学者提出是否可将和肽素作为急性期疾病的预后标志物
目的：本研究探讨应激标志物和肽素在判断急性缺血性脑卒中患者远期预后的价值。
方法：采用双抗体夹心实验方法，对245例以急性缺血性脑卒中收入院患者的入院后24小时内血浆和肽素水平进行测定。入院时、出院时、1年后患者的神经系统功能用美国国立卫生研究院卒中量表(NIHSS)评价；采用改良Rankin量表(mRS)衡量患者卒中后功能的结果。确定和肽素在预测1年内死亡率和功能预后价值。
结果：不良结局和死亡患者入院时和肽素水平显著增加（P<0.05）。通过多因素Cox回归分析调整的常见危险因素，结果表明，和肽素是功能预后（危险比=3.88；95%可信区间：1.94–7.77）和死亡（危险比=5.99；95%可信区间：2.55-14.07）的独立预测因素。和肽素功能预后的受试者工作特性曲线下面积为0.75（95%CI，0.70–0.82），死亡的受试者工作特性曲线下面积为0.867（95%CI，0.802–0.933）。
结论：和肽素可能成为预测急性缺血性卒中功能预后和1年死亡率的一个新的生物标志物。
Background：Stroke is the first leading cause of mortality in the China and one of theleading causes of severe morbidity.15to30%of stroke survivors will be permanentlydisabled. Abnormalities in endocrine function have been reported in acute ischemic strokewith activation of the hypothalamo-pituitary-adrenal axis being one of the first measurablephysiological responses to cerebral ischemia. Due to the positive association of copeptin withthe severity of illness and outcome, copeptin has been proposed as a prognostic marker inacute illness. Some studies have found that increased copeptin levels are associated withoutcome and (or) severity in patients with ischemic stroke, intracerebral hemorrhage,traumatic brain injury, transient ischemic attacks. This study aimed at prospectivelyevaluating the prognostic value of copeptin levels in a cohort of Chinese patients with anacute ischemic stroke.
Objective: The identification of patients at highest risk for adverse outcome who arepresenting with acute ischemic stroke to the emergency department remains a challenge. Thisstudy firstly investigates the long-term prognostic value of the stress marker copeptin inChinese patients with acute ischemic stroke.
Methods: In a prospective study, copeptin levels were measured using a sandwichimmunoassay on admission in plasma of245consecutive patients with an acute ischemicstroke. The prognostic value of copeptin to predict the functional outcome and mortalitywithin one year was compared with the National Institutes of Health Stroke Scale score andwith other known outcome predictors.
Results: Patients with an unfavorable outcomes and nonsurvivors had significantlyincreased copeptin levels on admission (P<0.05and P<0.05). Multivariate Cox regressionanalysis adjusted for common risk factors showed that copeptin was an independent predictor of functional outcome (hazard ratio=3.88;95%CI:1.94–7.77) and nonsurvivors (hazard ratio=5.99;95%CI:2.55-14.07). The area under the receiver operating characteristic curve ofcopeptin was0.75(95%CI,0.70–0.82) for functional outcome and0.867(95%CI,0.802–0.933) for mortality.
Conclusions: Copeptin levels are a novel and complementary biomarker to predictfunctional outcome and mortality1year after acute ischemic stroke.
目的：本研究探讨应激标志物和肽素在判断急性缺血性脑卒中患者远期预后的价值。
方法：采用双抗体夹心实验方法，对245例以急性缺血性脑卒中收入院患者的入院后24小时内血浆和肽素水平进行测定。入院时、出院时、1年后患者的神经系统功能用美国国立卫生研究院卒中量表(NIHSS)评价；采用改良Rankin量表(mRS)衡量患者卒中后功能的结果。确定和肽素在预测1年内死亡率和功能预后价值。
结果：不良结局和死亡患者入院时和肽素水平显著增加（P<0.05）。通过多因素Cox回归分析调整的常见危险因素，结果表明，和肽素是功能预后（危险比=3.88；95%可信区间：1.94–7.77）和死亡（危险比=5.99；95%可信区间：2.55-14.07）的独立预测因素。和肽素功能预后的受试者工作特性曲线下面积为0.75（95%CI，0.70–0.82），死亡的受试者工作特性曲线下面积为0.867（95%CI，0.802–0.933）。
结论：和肽素可能成为预测急性缺血性卒中功能预后和1年死亡率的一个新的生物标志物。
Background：Stroke is the first leading cause of mortality in the China and one of theleading causes of severe morbidity.15to30%of stroke survivors will be permanentlydisabled. Abnormalities in endocrine function have been reported in acute ischemic strokewith activation of the hypothalamo-pituitary-adrenal axis being one of the first measurablephysiological responses to cerebral ischemia. Due to the positive association of copeptin withthe severity of illness and outcome, copeptin has been proposed as a prognostic marker inacute illness. Some studies have found that increased copeptin levels are associated withoutcome and (or) severity in patients with ischemic stroke, intracerebral hemorrhage,traumatic brain injury, transient ischemic attacks. This study aimed at prospectivelyevaluating the prognostic value of copeptin levels in a cohort of Chinese patients with anacute ischemic stroke.
Objective: The identification of patients at highest risk for adverse outcome who arepresenting with acute ischemic stroke to the emergency department remains a challenge. Thisstudy firstly investigates the long-term prognostic value of the stress marker copeptin inChinese patients with acute ischemic stroke.
Methods: In a prospective study, copeptin levels were measured using a sandwichimmunoassay on admission in plasma of245consecutive patients with an acute ischemicstroke. The prognostic value of copeptin to predict the functional outcome and mortalitywithin one year was compared with the National Institutes of Health Stroke Scale score andwith other known outcome predictors.
Results: Patients with an unfavorable outcomes and nonsurvivors had significantlyincreased copeptin levels on admission (P<0.05and P<0.05). Multivariate Cox regressionanalysis adjusted for common risk factors showed that copeptin was an independent predictor of functional outcome (hazard ratio=3.88;95%CI:1.94–7.77) and nonsurvivors (hazard ratio=5.99;95%CI:2.55-14.07). The area under the receiver operating characteristic curve ofcopeptin was0.75(95%CI,0.70–0.82) for functional outcome and0.867(95%CI,0.802–0.933) for mortality.
Conclusions: Copeptin levels are a novel and complementary biomarker to predictfunctional outcome and mortality1year after acute ischemic stroke.
引文
[1] Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N,et al. Heart diseaseand stroke statistics-2008update: a report from the American Heart AssociationStatistics Committee and Stroke Statistics Subcommittee. Circulation,2008,117:25-146.
[2] Johansson A, Olsson T, Carlberg B, Karlsson K, Fagerlund M. Hypercortisolism afterstroke-partly cytokine-mediated. J Neurol Sci,1997,147:43-7.
[3] Volpi S, Rabadan-Diehl C, Aguilera G. Vasopressinergic regulation of thehypothalamic pituitary adrenal axis and stress adaptation. Stress,2004,7:75-83
[4] Katan M, Christ-Crain M.The stress hormone copeptin: a new prognostic biomarkerin acute illness. Swiss Med Wkly,2010,140: w13101.
[5]叶忠．Copeptin在心血管疾病中的研究[J]．国际心血管病杂志，2009，36(2)；105-107．
[6] Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, Bingisser R, et al.Copeptin: a novel, independent prognostic marker in patients with ischemic stroke.Ann Neurol,2009,66:799-808.
[7] Zhang X, Lu XM, Huang LF, Ye H. Copeptin is associated with one-year mortalityand functional outcome in patients with acute spontaneous basal ganglia hemorrhage.Peptides,2012,33:336-41.
[8] Zweifel C, Katan M, Schuetz P, Siegemund M, Morgenthaler NG, Merlo A, et al.Copeptin is associated with mortality and outcome in patients with acuteintracerebral hemorrhage. BMC Neurol,2010,26:34.
[9] Dong XQ, Huang M, Yang SB, Yu WH, Zhang ZY. Copeptin is associated withmortality in patients with traumatic brain injury. J Trauma,2011,71:1194-8.
[10] Katan M, Nigro N, Fluri F, Schuetz P, Morgenthaler NG, Jax F, et al. Stress hormonespredict cerebrovascular re-events after transient ischemic attacks. Neurology,2011,76:563-6..
[11] Lloyd-Jones D, Adams R, Carnethon M, et al. American Heart Association StatisticsCommittee and Stroke Statistics Subcommittee, Heart disease and stroke statistics-2009update：a report from the American Heart Association Statistics Committee andStroke Statistics Subcommittee. Circulation,2009, l19:480-486.
[12] Cheng XM，Ziegler DK，Lai YH，et a1．Stroke in China,1986through1990[J].Stroke,1995，26(11)：1990-1994．
[13] Thorvaldsen P，Kuulasmaa K, Rajakangas AM，et a1．Stroke trends in the WHOMONICA project[J]．Stroke,1997，28：500-506.
[14] Johnston SC, Clinical practice．Transient ischemic attack．N Engl J Med,2002,347:1687-1692.
[15] SIot KB, Berge E, Dorman P, et al. Oxfordshire Community Stroke Project, theInternational Stroke Trial(UK); Lothian Stroke Register．Impact of functional statusat six months on long term survival in patient with ischemic stroke：prospectivecohort studies. BMJ,2008,336:376-379.
[16] van der Worp HB, van Gijn J. Clinial practice. Acute ischemic stroke, N Engl JMed,2007，357：572-579.
[17] Valli G, Fedeli A, Antonucci R, et a1. Water and sodium imbalance in COPDpatients[J]. Monaldi Arch Chest Dis,2004,61(2):112-116.
[18] Friedmann AS, Malott KA, Memoli VA, et a1. Products of vasopressin geneexpression in small-cell carcinoma of the lung[J]. Br J Cancer,1994,69(2):260-263.
[19] Holwerda DA．A glycopeptide from the posterior lobe of pig pituitaries, I, Isolationand characterization[J]．Eur J Biochem,1972，28(3)：334-339.
[20] Kacan M，Morgenthaler N，Widmer I，et a1．Copeptin，a stable peptide derived fromthe vasopressin precursor，correlates with the indivldual stress level[J]．NeuroEndocrinol Lett，2008，29(3)：341-346．
[21] Katan M，Müller B，Christ-Crain M．Copeptin：a new and promising diagnosticand prognostic marker[J]. Crit Care，2008，12(2)：117．
[22] Watanabe I，Tani S，Nagao K，et al. Regulation of arginine vasopressin in the humanheart[J]．Circ J，2005，69(11)：1401-1404．
[23] Preibisz JJ, Sealey JE, Laragh JH et al. Plasma and platelet vasopressin in essentialhypertension and congestive heart failure[J]. Hypertension,1983;5:1129-38.
[24] Morgenthaler NG, Struck J, Alonso C, et a1. Assay for the measurement of copeptin,astable peptide derived from the precursor of vasopressin. Clin Chem,2006,52:112-119.
[25] Fenske W，Stork S，Blechschmidt A，et al. Copeptin in the differential diagnosis ofhyponatremia[J]．J Clin Endocrinol Metab，2009，94(1)：123-129．
[26] Nigro N，Müller B，Morgenthaler N，et al. The use of copeptin，the stable peptideof the vasopressin precursor，in the differential diagnosis of sodium imbalance inpatients with acute diseases[J]．Swiss Med Wkly，20l1，141：w13270．
[27] Nagy G, Mulchahey JJ, Smyth DG, et al.The glycopeptides moiety ofvasopressin-neurophysin precursor is neurohypophysial prolactin releasing factor[J].Biochem Biophys Res Commun,1988,151:524-529.
[28] Barat C, Simpson L, Breslow E. Properties of human vasopressin precursorconstructs: Inefficient monomer folding in the absence of copeptin as a potentialcontributor to diabetes insipidus[J]. Biochemistry,2004,43:8191-8203.
[29] Katan M, Morgenthaler NG, Dixit KC, et a1. Anterior and posterior pituitary functiontesting with simultaneous insulin tolerance test and a novel copeptin assay[J]. J ClinEndocrinol Metab,2007,92(7):2640-3.
[30] Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from thevasopressin precursor, is elevated in serum of sepsis patients. Peptides,2005,26:2500-2504.
[31] Chenevier-Gobeaux C, Freund Y, C1aessens Y E, et a1. Copeptin for rapid rule out ofacute myocardial infartion in emergency department[J]．Inl J Cardiol，2011，Nov18．
[32] De Marchis GM，Katan M，Weck A，et al. Copeptin adds prognostic information afterischemic stroke:Results from the CoRisk study[J]. Neurology，2013，80(14):127812-86.
[33] Boeck L, Eggimann，P, Smyrnios N, et a1. The sequential organ failure assessmentscore and copeptin for predicting survival in ventilator-associated pneumonia[J]．JCrit Care,2012,27(5):523.e1-9
[34] Khan SQ，Dhillon OS，O’Brien RJ，et a1．C-terminal provasopressin(copeptin)asa novel and prognostic marker in acute myocardial infarction：Leicester AcuteMyocardial Infarction Peptide(LAMP)study[J]．Circulation，2007，115(16)：2103-2110．
[35] T lg R, Witt M，Schwarz B，et a1．Comparison of carvedilol and metoprolol inpatients with acute myocardial infarction undergoing primary coronaryintervention--the PASSAT Study[J]．Clin Res Cardiol．2006，95(1)：31-41．
[36] Fukuzawa J, Haneda T, Kikuchi K. Arginine vasopressin increases the rate of proteinsynthesis in isolated perfused adult rat heart via the V1receptor[J]. Mol CellBiochem.1999,195(1-2):93-98．
[37] Chai SB, Hui YM, Li XM, et a1. Plasma levels of copeptin in patients with coronaryheart disease[J]. Heart Vessels,2009,24(2):79-83.
[38] M ckel M, Danne O, Müller R, et al.Development of an optimized multimarkerstrategy for early risk assessment of patients with acute coronary syndromes[J].ClinChim Acta,2008,393:103-109.
[39] Dieplinger B, Gegenhuber A, Haltmayer M, et al. Evaluation of novel biomarkers forthe diagnosis of acute destabilised heart failure in patients with shortness ofbreath[J]．Heart,2009,95(18):1508-1513．
[40] Reichlin T, Hochholzer W, Stelzig C, et a1．Incremental value of copeptin for rapidrule out of acute myocardial infarction[J]．J Am Coil Cardiol,2009,54(1)：60-68．
[41]王晓艳，杨侃，孙明等．脑钠肽、和肽素和高敏C反应蛋白与急性冠状动脉综合征的相关性[J]．中国动脉硬化杂志，2009，17（3）：229-231．
[42]祝烨．慢性心力衰竭治疗进展．现代临床医学．2007，33(2)：148-150.
[43]治尉．精氨酸血管加压素与心力衰竭研究的进展[J]．心血管病学进展.2009,30(1)：95-99．
[44] Stoiser B，M rtl D，Hülsmann M，et al．Copeptin，a fragment of the vasopressinprecursor, as a novel predictor of outcome in heart failure[J]．Eur JClin Invest．2006,36(11)：771-778．
[45] Gegenhuber A．Struck J，Dieplinger B，et a1．Comparative evaluation of B-typenatriuretic peptide, Mid-regional pro-A-type natriuretic peptide． Mid-regionalpro-adrenomedullin, and copeptin to predict1-year mortality in patients with acutedestabilized heart failure[J]．J Card Fail，2007，13(1):42-49.
[46] Neuhold S, Huelsmann M，Strunk G, et a1. Comparison of copeptin，B-typenatriuretic peptide，and amino-terminal pro-B-type natriuretic peptide in patients withchronic heart failure：prediction of death at different stages of the disease[J]．J AmCoil Cardiol，2008，52(4):266-272.
[47] Tang WH，Flancis GS，Morrow DA，et aI．National academy of clinical biochemistrylaboratory medicine practice guidelines： clinical utilization of cardiac biomarkertesting in heart failure[J]．Circulation，2007，116(5)：99-109．
[48] Kelly D, Squire IB, Khan SQ, et a1. C-terminal provasopressin(copeptin)isassociated with left ventricular dysfunction, remodeling, and clinical heart failure insurvivors of myocardial infarction[J]. J Card Fail,2008,14(9):739-745.
[49] Voors AA, von Haehling S, Anker SD, et a1. C-terminal pro-vasopressin (copeptin)isa strong prognostic marker in patients with heart failure after an acute myocardialinfarction results from the OPTIMAAL study[J1．Eur Heart J，2009，30(10)：1187-1194．
[50] Alvarez-Sabin J，Delgado P，Abilleira S，et a1．Temporal profile of matrixmetallopromirmes and their inhibitors after spontaneous intracerebral hemorrhage：relationship to clinical and radiological outcome．Stroke,2004,35：1316-1322．
[51] Ferro JM. Update on intracerebral haemorrhage [J]. J Neurol,2006,253(8):985-999.
[52] Delgado P, Alvarez Sabin J, Montaner J. Biological markers in spontaneousintracerebral hemorrhage. Neurologia,2007,22:448-455.
[53] Zweifel C，Katan M，Schuetz P，et a1．Copeptin is associated with mortality andoutcome in patients with acute intracerebral hemorrhage．BMC Neurol，2010,10:34.
[54] Fassbender K, Schmidt R, Mossner R, et a1． Pattern of activation of thehypothalamic-pituitary-adrenal axis in acute stroke．Relation to acute confusionalstate，extent of brain damage, and clinical outcome．Stroke．1994．25：l105-l108．
[55] Slowik A, Turaj W，Pankiewicz J，et a1．Hypercortisolemia in acute stroke is relatedto the inflammatory respone．J Neurol Sci，2002，196：27-32．
[56] Volpi S， Rabadm-Diehl C， Aguilera G． Vasopressinersic regulation of thehypothalamic pituitary adrehal axis and stress adaptation．Stress,2004，7：75-83．
[57] Sapolsky RM．Pulsinelli WA．Glucocorticoids potentiate ischemic injury to neurons：therapeutic implicatiom．Science，1985，229：1397-1400．
[58] Smith-Swintosky VL, Pettigrew LC, Sapolsky RM, et al. Metyrapone, an inhibitor ofglucocorticoid production, reduces brain injury induced by focal and global ischemiaand seizures. J Cereb Blood Flow Metab,1996,16:585-598
[59] Potocki M，Breidthardt T，Mueller A，et a1．Copeptin and risk stralification inpatients with acute dyspnea [J]．Criti Care，20l0，14(6)：R213．
[60] Stolz D，Christ-Crain M，Morgenthaler NG，et al. Copeptin，C-reaccive protein，and procalcitonin as prognostic biomarkers in acute exacerbation of COPD[J].Chest，2007，13l(4)：1058-1067．
[61] Boeck L，Eggimann P，Smyrnios N，et a1．The sequential organ failure assessmentscore and copeptin for predicting survival in ventilator-associated pneumonia[J]．JCrit Care，20l2，27(5)：523．
[62] Müller B，Morgenthaler N，stolz D，el al Circulating levels of copeptin，a novelbiomarker，in lower respiratory tract infections[J]．Eur J Clin Invest，2007，37(2)：145-152．
[63] Saleem U，Khaleghi M，Morgenthaler NG，et a1．Plasma carboxy-terminalprovasopressin (copeptin)：a novel marker of insulin resistance and metabolicsyndrome[J]．J Clin Endocrinol Metab，2009．94(7)：2558-2564．
[64] Enhorning S，Wang TJ，Nilsson PM，et a1．Plasma copeptin and the risk of diabetesmellitus[J]．Circulation，2010，121(19)：2102-2108．
[65] Oghlakian G，Klapholz M．Vasopressin and vasopressin receptor antagonisls in heartfailure[J]．Cardiol Rev，2009，17(1)：10-15．
[66] Jochberger S, Morgenthaler NG, Mayr VD, et a1. Copeptin and arrginine vasopressinconcentrations in critically ill patients[J]．J Clin Endocrinol Melab,2006,91(11)：4381-4386.
[67] Jochberger S，Luckner G，Mayr VD，et a1．Course of vasopressin and copeptinplasma concentrations in a patient with severe septic shock[J]．Anaesth IntensiveCare,2006,34(4)：498-500.
[68]肖洋,张基刚,柴三葆.多种疾病患者血浆copeptin测定[J].放射免疫学杂志,2008,21(2)：97-100.
[69] Benzing J，Wellmann S，Achini F，et al. P1asma copeptin in preterm infants：a highlysensitive marker of fetal and neonatal stress[J]．J Clin Endocrinol Metab，2011，96(6)：982-985．
[70] Müller B, Morgenthaler N, Christ-Crain M, et a1. Circulating levels of copeptin, anovel biomarker, in lower respiratory tract infections[J]．Eur J Clin Invest，2007，37(2)：145-152．
[71] Szinnai G，Morgenthaler NG，Berneis K，et a1．Changes in plasma copeptin，thec-terminal portion of arginine vasopressin during water deprivation and excess inhealthy subjects[J]. J clin Endocrinol Metab，2007，92(10)：3973-3978．
[72] Morgenthaler NG，Müller B，Struck J．et a1．Copetin，a stable peptide of the argininevasopressin precursor, is elevated inhemorrhagic and septic shock[J]．Shock，2007，28(2):219-26.
[73] Wellmann S，Benzing J，Cippa G，et al. High copeptin concentrations in umbilicalcord blood after vaginal delivery and birth acidosis[J]．J Clin Endocrinol Metab，2010，95(11)：5091-5096．
[74] Morgenthaler NG，Struck J，Jochberger S，et a1．Copeptin：clinical use of a newbiomarker[J].Trends Endocrinol Metab，2008，19(2)：43-49.
[75] Katan M，Morgenthaler N，Widmer I，et a1．Copeptin，a stable peptide delived fromthe vasopressin precursor， correlates with the individual stress level[J].NeuroEndocrinol Lett，2008，29(3)：341-346.
[76] Meijer E，Bakker SJ，Halbesma N，et a1．Copeptin，a surrogate marker ofvasopressin，is associated with microalbuminuria in a large population cohort[J]．Kidney Int，20l0，77(1)：29-36．
[77] Dunser MW，Schmittinger CA，Torgersen C． Copeptiln and the transplantedkidney：friends or foes?[J]. Transplantation，2009，88(4)：455-456．
[78] Liebetrau C，Nef H，Szardien S，et al. Release kinetics of copeptin in patientsundergoing transcoronary ablation of septal hypertrophy[J]. Clin Chem，2013，59(3):566-569.
[79]张林峰，杨军，武阳丰等．我国人群中缺血性和出血性脑卒中发病的相对比例．中华内科杂志[J]．2003，42：94-97.
[80]饶明俐．中国脑血管病防治指南[M]．北京：人民卫生出版社，2007：1-24．
[81] Zhou H，Wang YJ，Wang SX，et a1．TOAST subtyping of acute ischemicstroke[J]．Zhonghua Nei Ke Za Zhi．2004，43(7):495-498.
[82] Adams HP Jr，Bendixen BH，Kappelle LJ，et a1．Classification of subtype of acuteischemic stroke.Definition for use in a multicenter clinical trial．TQAST．Trial of Org10172in Acute Stroke Treatment．Stroke,1993,24(1)：35-41．
[83] Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in theterritory of a symptomatic intracranial arterial stenosis Circulation [J].2006,113:555-63.
[84] Higashida RT, Meyers PM, Connors JJ, et al. Intracranial angioplasty and stenting forcerebral atherosclerosis: a position statement of the American Society ofInterventional and Therapeutic Neuroradiology, Society of Interventional Radiology,and the American Society of Neuroradiology[J]. J Vasc Interv Radiol.2005,16:1281-1285
[85]王桂红,王拥军,姜卫剑等.缺血性脑卒中患者脑动脉狭窄的分布及特征[J].中华老年心脑血管病杂志.2003,5:315-317
[86] Lee SJ, Cho SJ, Moon HS, et al. Combined extracranial and intracranialatherosclerosis in Korean patients[J].Arch Neurol.2003,60:1561-1564.
[87] Arenillas JF, Molina CA, Chacón P, et al.High lipoprotein (a), diabetes, and theextent of symptomatic intracranial atherosclerosis[J]. Neurology.2004,63:27-32.
[88] Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebralarteries: intracranial versus extracranial[J]. Neuroepidemiology.2003,22:37-40.
[89] Kuller LH. Epidemiology and prevention of stroke, now and in the future[J].Epidemiol Rev,2000,22:14-17
[90] Hu G, Sarti C, Jousilahti P, et al. The impact of history of hypertension and type2diabetes at baseline on the incidence of stroke and stroke mortality [J]. Stroke,2005,36:2538-2543
[91] Weikert C, Berger K,Heidemann C, et al. Joint effects of risk factors for stroke andtransient ischemic attack in a German population: the EPIC Potsdam Study[J].Neurology,2007,254:315-21
[92] Vivancos-Mora J, Gil-Nunez AC. Lipids and stroke: the opportunity oflipid-lowering treatment[J]. Cerebrovasc Dis,2005,20:53-67.
[93] Pinto A, Tuttolomondo A, Di Raimondo D, et al.Cerebrovascular risk factors andclinical classification of strokes[J].Semin Vasc Med,2004,4:287-303.
[94] Tanizaki Y, Kiyohara Y, Kato I，et a1．Incidence and risk factors for subtypes ofcerebral infarction in a general population：the Hisayama study[J]．Stroke,2000,31(11)：2616-2622．
[95] Syed NA，Khealani BA，Ali S,et a1．Ischemic stroke subtypes in Pakistan：the AgaKhan University Stroke Data Bank[J]．J Pak Med Assoc,2003，53(12)：584．
[96] Lovett JK,Coull AJ，Rothwell PM．Early risk of recurrence by subtype of ischemicstroke in population-based incidence studies[J]．Neurology,2004，62(4)：569-573．
[97] Bamford J，Sandercock P，Dennis M，et a1．Classification and natural history ofclinically identifiable subtypes of cerebral infarction[J]. Lancet,1991,337:1521-1526.
[98] Mead GE，O’Neill PA，Farrell JL, et a1．Does the Oxfordshire Commtmity Strokeproject classification predict the site of cerebral infarction?[J]. CerebrovascularDiseases,1996，6suppl2：155．
[99] Mead GE，Lewis SC，Wardlaw JM，et a1．How well does the Oxfordshire ofCommunity Stroke Project classification predict the site and size the infarct on brainimaging?[J]. J Neurol Neurosurg Psychiatry,2000，68：558-562．
[100] Mead GE, Wantlaw JM, Dennis MS, et al. Relationship between pattern ofintraeranial artery abnormalities on transcranial doppler and Oxfordshire CommunityStroke Project clinical classification of ischemic stroke[J]. Stroke,2000,31(3):714-719.
[101] Stum JW, Dewey HM, Donnan GA, et al. Handicap after stroke: how does it relate todisability, perception of recovery, and stroke subtype?: the north North EastMelbourne Stroke Incidence Study(NEMESIS)[J]．Stroke,2002，33：762-768．
[102] Kobayashi A, Wardlaw JM, Lindley RI, et al. Oxfordshire community stroke projectclinical stroke syndrome and appearances of tissue and vascular lesion onpretreatment CT in hyperacute ischemic stroke among the first510patients in theThird International Stroke Trial(IST-3)[J]. Stroke,2009,40(3):743-748.
[103] Hallstrom B, Norrving B, Lindgren A. Stroke in lund-orup, Sweden: improvedlong-term survival among elderly stroke patients[J]. Stroke,2002,33(6):1624-1629
[104] Staals J，Van Raak L，Hilton A，et a1．Differences in long-term survival in twolacunar stroke types：a15-year follow-up study in782cerebral infarct patients[J]．Cerebrovasc Dis,2008，25(1-2)：26-31．
[105] Feuerstein GZ, LiuT, BaroneFC. Cytokines, inflammation, and brain injure: Role oftumor necrosis factor-alpha. Cerebrovase brain Metab Rev,1994,6(4):341-360.
[106] Arvin B, Neville LF, Barone PC, et al. The role of inflannation and cytokines in braininjury. Neurosci Biobehave Rev,1996,20(33):445-452.
[107] Kubes P, Grisham MB, Barromen JA, et al. Leukocyte-induced vascular proteinleakage in Cat meseniery. Am J Physiol,1991,261: HI827-879.
[108] Jerome SN, Akinmetsu T, Korthuis RJ. Leukoeyte adhesion, edema, anddevelopment of postisehemic capillary no-refiow. Am JP hysiol,1994,267:H1329-336.
[109] Miyashita K, Abe H, Nakajima T, et al. Glutamate release in the gerbil hippocampusafter middle cerebral artery oeclusion. Neuroreport,1994,5:945-948.
[110] Osuga H, Hakin AM. Relationship between estracellular glutamate concentration andvoltge sensitive caleium channelfunction in fieal ischemia in the rat. J Cereb BloodFlow Metab,1996,16629-636.
[111] Fujiwara N, Abe T, Endoh H, et al. Changes in intraeellrllar pH of hippocampal slicesresponding tohypoxia and/or glueose depletion. Brain Res,1992,572:335-342.
[112] Siesjo BK. PathoPhysiology and treatment of foealeerebral isehemic. PartⅡ,meehanisms of damage and treatment. J Nerrosurg,1992,77:337-342.
[113] Wood NI, Barone Pc, Benham CD, et al. The effects of SB206284A, a novelneuronal caleium channel antagonist, in models of cerebral ischemia. J Cereb BloodFlow Mctab,1997,17(4):421-429.
[114] Bedsen DE. Neural apoptosis.Ann Neurol,1995,38:839-851.
[115] Koh JY, Suh Sw, Gwag BJ, et al. The role of zinic in selective neuronal deathfollowing transient global isehemia. Seienee,1996,272:1013-1016.
[116] Nagayama M, Niwa K, Nagayama T, et al. The cyelooxygenase2inhibitor NS-398ameliorates ischemic brain injure in wild-type mice but not in mice with deletion ofthe indueible nitric oxide synthase gene. J Cereb Blood Flow Metab,1999,19(11):1212-1219.
[117] Holroyol-Ledue JM，Kapral MK Austin PC，et a1．Sex difference and similarities inthe management and outcome of stroke patients[J]．Stroke．2000，31：1833-1837．
[118] Lobo RA．Menopause and stroke and the effects of hormonal therapy [J]．Climacteric,2007,12：27-31．
[119] Homer S，Niederkom K Schnabl S，et a1．Gender aspects of Ischemic stroke．Ananalysis of the Austrian Stroke-Unit Registry[J]．Wien Med Wochenschr．2008，158(15-16)：446-452．
[120] Saini M，Shuaib A．Stroke in women[J]．Recent Pat Cardiovasc Drag Discov,2008,3(3)：209-221．
[121] Billeci AM，Paciaroni M，Caso V，et a1．Hormone replacement therapy andStroke[J]．Curt Vase Pharmacol,20086(2)：112-123．
[122] Olsen TS，Dehlendorff C，Andersen KK．Gender differences in stroke mortalityrate[J]．Neuroepidemiology．2007，29(3-4)：218-225．
[123] Lai SM，Duncan PW，Dew P，et a1．Sex differences in stroke recovery [J]．PrevChronic Dis,2005,2(3): A13.
[124] Robinsion-Smith G, Johnston MV, Alien J，et a1．Self-care self-effieaey, quality oflife, and depression after stroke[J]. Arch Phy Rehabil,2000,81:460-464.
[125] De Jong G, van Raak L, Kessels F, et al. Stroke subtype and mortality, a follow-upstudy in998patients with a first cerebral infarct[J]. J Clin Epidemiol,2003,56：262-268.
[126] Hart CL, Hole DJ, Smith GD et al.comparison of risk factors for stroke incidenceand stroke mortality in20years or follow up in men and women in the Renfrewpaisley study in Scotland[J]. Stroke,2000,31(8):1893-1896.
[127] Minn YK, Cho SJ, Kim SG, et al. Long-term outcomes of acute ischemic stroke inpatients ages80years and older[J]. Yonsei Med J,2008,49(3):400-404.
[128] Morales-Ortiz A，Jimenez-Pascual M. Fever of central origin during stroke [J]．RevNeurol．2001,32(12)：1111-1114．
[129] Greer DM，Funk SE，Reaven NL，et a1．Impact of fever on outcome in patients withstroke and neurologic injury：a comprehensive meta-analysis[J]．Stroke,2008,39(11)：3029-3035．
[130] Fernandez A, Schmidt JM, Claassen J, et al. Fever after subarachnoid hemorrhage:risk factors and impact on outcome[J]. Neurology,2007,68(13):973-974.
[131] Kammersagaard LP, Jorgensen HS. Admission body temperature predicts long-termmortality after acute stroke[J]. Stroke,2002,33(7):1759-1762.
[132] De Georgia MA，Krieger DW，Abou-Chebl A，et a1．Cooling for acute ischemicbrain damage(COOL AID)： a feasibility trial of endovascular cooling [J].Neurology．2004，63：312-317．
[133] Olsen TS, Weber UJ, Kammersgaard LP. Therapeutic hypothermia for acute stroke[J].Lancet Neurol,2003,2(7):410-416.
[134]彩霞，周钦，黄载文．亚低温、低温治疗重症脑卒中疗效观察[J]．中西医结合心脑血管病杂志,2007，5(9)：898-899．
[135] Abboud H，Labreuche J，Plouin F, et a1．Hi．gh blood pressure in early acute stroke：a sign of a poor outcome[J].J Hypertens,2006,24(2)：381-386．
[136] Yong M，Kaste M．Association of characteristics of blood pressure profiles andstroke outcomes in the ECASS-II trial[J]．Stroke,2008，39(2)：366-372．
[137] Willmot M，Leonardi-Bee J，Bath PMW．High blood pressure in acute stroke andsubsequent outcome[J]．A Systematic Review．Hypertension,2004，43：18-24．
[138] Leonardi-Bee J, Bath PMW, Phillips SJ, et a1．Blood pressure and clinical outcomein the International Stroke Trial[J]．Stroke,2002,33：1315-1320．
[139] Cassidy E，O’Connor R,0’Keane V. Prevalence of post-stroke depression in an Irishsample and its relationship with disability and outcome following inpatientrehabilitation[J]．Disabil Rehabil,2004,26(2)：71-77．
[140]龙洁，刘永珍．卒中及抑郁状的发生及相关因素研究[J]．中华神经科杂志,2001，34(9)：145．
[141]温萍，李旭方，刘满芬等.汕头地区脑卒中后遗症患者抑郁症发病率及其对生活质量的影响[J].华北煤炭医学院学报，2008,10（4）：451-452.
[142]勾丽洁，许士奇，刘旭东等．脑卒中后抑郁的发生率及其对运动功能恢复的影响[J].承德医学院学报，2008,25（3）：251-253.
[143] Berg A，Palomaki H，Lehtihalmes M，et a1．Poststroke depression：an18-monthfollow-up[J]．Stroke．2003，34(1)：138-143．
[144] Saxena SK, Ng TP, Koh G, et al. Is improvement in impaired cognition anddepressive symptoms in post-stroke patients associated with recovery in activities ofdaily living?[J]. J Stroke Cerebrovasc Dis,2004,13(5):220-227.
[145]繆鸿石，朱镛连.急期性脑卒中的康复评定和治疗[M].北京：华夏出版社，1996:141-144.
[146] Elkind MS, Cheng J, Rundek T, et al. Leukocyte count predicts outcome afterischemic stroke: the Northern Manhattan Stroke Study[J]. J Stroke Cerebrovasc Dis,2004,13(5):220-227
[147]韩俊英，夏颖华.血清白细胞介素-6对缺血性脑卒中患者预后的影响[J].中国老年保健医学，2008,6（4）：14-16.
[148] Waje-Andreassen U，Kfftkenes J，Ulvestad E，et a1．IL-6：an early marker foroutcome in acute ischemic stroke[J]．Acta Neurol Scand．2005Jun，111(6)：360-365．
[149] Kazmierski RGuzik P，et al.Predictive value of white blood cell count on admissionfor in-hospital mortality in acute stroke patients． Clini[J]． NeurolNeurosurgery．2004，107(1)：38-43．
[150] Rallidis LS，Vikelis M，Panagiotakos DB，et a1．Inflammatory markers andin-hospital mortality in acute ischaemic stroke[J]．Atherosclerosis．2006,189(1)：193-197．
[151] Szczudlik A，Slowik A，Turaj W，et a1．Transient hyperglycemia in ischemia strokepatients[J]．J Neurol Sci．2001，189(1-2)：1005-1011．
[152] Els T，Klisch J，Orszagh M，et a1．Hyperglycemia in patient swith focal cerebralischemia after intravenous thrombolysis·influence on clinical outcome and infarctsize[J]．Cerebrovasc Dis．2002，13(2)：89-94．
[153] Garg R Chaudhuri A，Munschauer F，et a1．Hyperglycemia, insulin, a acute ischemicstroke：a mechanistic justification for atrial of insulin infusion therapy [J]．Stroke,2006，37(1):267-273.
[154]林亚新，周茵，关东威.应激性血糖增高对急性脑卒中预后影响的临床研究[J].中国老年学杂志，2005,25（6）：617-619.
[155] Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and prognosis of strokein nondiabetic and diabetic patient: systematic overview[J]. Stroke,2001,32:2426-2432.
[156]陈静.应激性血糖增高对急性脑卒中预后影响的临床研究[J].医学理论与实践,2008,21(5):538-539.
[157] Becker K. Intensive care unit management of the stroke patient[J]. Neurol clin,2000,18(2):439-545.
[158] Rudd AG, Hoffman A, Irwin P, et al. Stroke unit care and outcome: resuits from the2001National Sentinel Audit of Stroke(England Wales, and Northern Ireland)[J].Stroke,2005,36:103-106.
[159] Langhorne P, Dey P, Woodman M, et al. Is stroke unit care portable? A systematicreview of the clinical trials[J]. Age Ageing,2005,34:324-330.
[160]王拥军.卒中单元[M].北京：科学技术文献出版社，2004:5-33.
[161]饶明俐.中国脑血管病防治指南[M].北京：人民卫生出版社，2007：110-114.
[162] Evers SM, Struijs JN, Ament AJ, et al. International comparison of stroke coststudies[J]. Stroke,2004,351(51):1209-1215.
[163] Yoneda Y, Uehara T, Yamasakl H, et al. Hospital based study of the care and cost ofacute ischemic stroke in Japan[J]. Stroke,2003,34(3):718-724.
[164]石玲燕，金嵘，郑荣远等.温州地区脑卒中住院患者费用分析[J].中国公共卫生，2006，22（8）：1022-1023
[165]刘力生．中国高血压防治指南[M]．2005年修订版．北京：人民卫生出版社，2005：18．2l
[166]钱荣立．中国糖尿病防治指南[M]．北京：北京大学医学出版社，2004：12．16．
[167]叶任高，陆再英．内科学[M]．第6版．北京：人民卫生出版社，2004：821．831．
[168] Lee TH，Hsu WC，Chen CJ，et a1．Etiologic study of young ischemic stroke inTaiwan[J]．Stroke，2002，33：1950-1955．
[169] Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, et al. Copeptin: a novel,independent prognostic marker in patients with ischemic stroke. Ann Neurol,2009,66:799-808.
[170] Pullicino P, Nelson KF, Kendall BE, et al. Small deep infarcts diagnosed oncomputed tomography [J]. Neurology,1980,30:1090
[171] Bonita R BR. Modification of Rankin Scale: recovery of motor function after stroke.Stroke,1988,19:1497-500.
[172] Xuedon g Liu, Yali L v, Bo Wang, et al. Pr edict ion of fun ct ional out com e ofischem ic st roke pat ient s in northwest China. Clinical Neurology an d Neurosurgery,2007,109(4):571-577.
[173]张断荣,张文禹,林素君.31例脑卒中患者ADL能力评价与康复训练[J].中国康复,1995,10(4):17.
[174] Sanders DE. Measurment of infarct size using MRI predict s prognosis in middlecerebral art ery infarction [J]. Stroke,1995,26:2272.
[175] Johansson BB, Jadback G, Norrving B, et al. Evaluation of longterm functional statusin first-ever stroke patients in a difined population [J]. Scand J Rehabil Med.1992,26(suppl):105-14.
[176] Johnston SC．Clinical practice．Transient ischemic attack．N Engl J Med,2002,347:1687-1692．
[177] Whiteley W, Chong WL, Sengupta A, Sandercock P. Blood markers for the prognosisof ischemic stroke: a systematic review. Stroke,2009,40:380-389.
[178] Di Napoli M, Papa F, Bocola V. Prognostic infuence of increased C-reactive proteinand fbrinogen levels in ischemic stroke. Stroke,2001,32:133–8.
[179] Elkind MS, Tai W, Coates K, et al. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med,2006,166:2073–80.
[180] Shantikumar S, Grant PJ, Catto AJ, et al. Elevated C-reactive protein and long-termmortality after ischaemic stroke: relationship with markers of endothelial cell andplatelet activation. Stroke,2009,40:977-979.
[181] Whiteley W, Jackson C,Lewis S,et al. Inflammatory markers and poor outcomeafter stroke: a prospective cohort study and systematic review of interleukin-6. PlosMed2009,6:e1000145
[182] Kelly PJ, Morrow JD, Ning M, et al. Oxidative stress and matrix metalloproteinase-9in acute ischemic stroke. The Biomarker Evaluation for Antioxidant Therapies inStroke (BEAT-Stroke) study. Stroke,2008,39:100-104.
[183] Del Zoppo GJ, Levy DE, Wasiewski WW, et al. Hyperfbrinogenemia and functionaloutcome from acute ischemic stroke. Stroke,2009,40:1687-1691.
[184] Whiteley W, Rumley A, Sattar N, et al. POS11blood markers and poor outcome afteracute cerebrovascular disease: a prospective cohort study. J Neurol NeurosurgPsychiatry,2010,81: e70.
[185] Neidert S, Katan M, Schuetz P, et al. Anterior pituitary-axis hormones and outcomein acute ischemic stroke. J Intern Med,2011,269:420-432.
[186] Urwyler SA, Schuetz P, Fluri F, et al. Prognostic value of copeptin: one-year outcomein patients with acute stroke. Stroke,2010,41:1564-1567.
[187] Nickel CH, Bingisser R, Morgenthaler NG. The role of copeptin as a diagnostic andprognostic biomarker for risk stratification in the emergency department. BMC Med,2012,10:7.
[188] Meisel A, Meisel C, Harms H, Hartmann O, Ulm L. Predicting post-stroke infectionsand outcome with blood-based immune and stress markers. Cerebrovasc Dis,2012,33:580-588.
[189] De Marchis GM, Katan M, Weck A, et al. Copeptin and risk stratification in patientswith ischemic stroke and transient ischemic attack: The CoRisk Study. Int J Stroke,2012, doi:10.1111/j.1747-4949.2011.00762.x.
[190] Shuaib A, Xu Wang C, Yang T, Noor R. Effects of nonpeptide V(1) vasopressinreceptor antagonist SR-49059on infarction volume and recovery of function in afocal embolic stroke model. Stroke,2002,33:3033-3037.
[191] Rose CE Jr, Anderson RJ, Carey RM. Antidiuresis and vasopressin release withhypoxemia and hypercapnia in conscious dogs. Am J Physiol1984;247:R127-134.
[192] Jochberger S, Mayr VD, Luckner G, et al. Serum vasopressin concentrations incritically ill patients. Crit Care Med,2006,34:293-299.
[193] Armstead WM. Vasopressin-induced protein kinase C-dependent superoxidegeneration contributes to atp-sensitive potassium channel but not calcium-sensitivepotassium channel function impairment after brain injury. Stroke,2001,32:1408-1414.
[194] Vakili A, Kataoka H, Plesnila N. Role of arginine vasopressin V1and V2receptorsfor brain damage after transient focal cerebral ischemia. J Cereb Blood Flow Metab,2005,25:1012-1019.
[195] Kozniewska E, Gadamski R, Klapczynska K, et al. Morphological changes in thebrain during experimental hyponatremia. Do vasopressin and gender matter FoliaNeuropath,2008,46:165-170.
[196] Kozniewska E, Romaniuk K. Vasopressin in vascular regulation and waterhomeostasis in the brain. J Physiol Pharmacol,2008,59(Suppl8):109-116.
[197] Potocki M, Breidthardt T, Mueller A. Copeptin and risk stratification in patients withacute dyspnea. Critical Care,2010,14：213...
[2] Johansson A, Olsson T, Carlberg B, Karlsson K, Fagerlund M. Hypercortisolism afterstroke-partly cytokine-mediated. J Neurol Sci,1997,147:43-7.
[3] Volpi S, Rabadan-Diehl C, Aguilera G. Vasopressinergic regulation of thehypothalamic pituitary adrenal axis and stress adaptation. Stress,2004,7:75-83
[4] Katan M, Christ-Crain M.The stress hormone copeptin: a new prognostic biomarkerin acute illness. Swiss Med Wkly,2010,140: w13101.
[5]叶忠．Copeptin在心血管疾病中的研究[J]．国际心血管病杂志，2009，36(2)；105-107．
[6] Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, Bingisser R, et al.Copeptin: a novel, independent prognostic marker in patients with ischemic stroke.Ann Neurol,2009,66:799-808.
[7] Zhang X, Lu XM, Huang LF, Ye H. Copeptin is associated with one-year mortalityand functional outcome in patients with acute spontaneous basal ganglia hemorrhage.Peptides,2012,33:336-41.
[8] Zweifel C, Katan M, Schuetz P, Siegemund M, Morgenthaler NG, Merlo A, et al.Copeptin is associated with mortality and outcome in patients with acuteintracerebral hemorrhage. BMC Neurol,2010,26:34.
[9] Dong XQ, Huang M, Yang SB, Yu WH, Zhang ZY. Copeptin is associated withmortality in patients with traumatic brain injury. J Trauma,2011,71:1194-8.
[10] Katan M, Nigro N, Fluri F, Schuetz P, Morgenthaler NG, Jax F, et al. Stress hormonespredict cerebrovascular re-events after transient ischemic attacks. Neurology,2011,76:563-6..
[11] Lloyd-Jones D, Adams R, Carnethon M, et al. American Heart Association StatisticsCommittee and Stroke Statistics Subcommittee, Heart disease and stroke statistics-2009update：a report from the American Heart Association Statistics Committee andStroke Statistics Subcommittee. Circulation,2009, l19:480-486.
[12] Cheng XM，Ziegler DK，Lai YH，et a1．Stroke in China,1986through1990[J].Stroke,1995，26(11)：1990-1994．
[13] Thorvaldsen P，Kuulasmaa K, Rajakangas AM，et a1．Stroke trends in the WHOMONICA project[J]．Stroke,1997，28：500-506.
[14] Johnston SC, Clinical practice．Transient ischemic attack．N Engl J Med,2002,347:1687-1692.
[15] SIot KB, Berge E, Dorman P, et al. Oxfordshire Community Stroke Project, theInternational Stroke Trial(UK); Lothian Stroke Register．Impact of functional statusat six months on long term survival in patient with ischemic stroke：prospectivecohort studies. BMJ,2008,336:376-379.
[16] van der Worp HB, van Gijn J. Clinial practice. Acute ischemic stroke, N Engl JMed,2007，357：572-579.
[17] Valli G, Fedeli A, Antonucci R, et a1. Water and sodium imbalance in COPDpatients[J]. Monaldi Arch Chest Dis,2004,61(2):112-116.
[18] Friedmann AS, Malott KA, Memoli VA, et a1. Products of vasopressin geneexpression in small-cell carcinoma of the lung[J]. Br J Cancer,1994,69(2):260-263.
[19] Holwerda DA．A glycopeptide from the posterior lobe of pig pituitaries, I, Isolationand characterization[J]．Eur J Biochem,1972，28(3)：334-339.
[20] Kacan M，Morgenthaler N，Widmer I，et a1．Copeptin，a stable peptide derived fromthe vasopressin precursor，correlates with the indivldual stress level[J]．NeuroEndocrinol Lett，2008，29(3)：341-346．
[21] Katan M，Müller B，Christ-Crain M．Copeptin：a new and promising diagnosticand prognostic marker[J]. Crit Care，2008，12(2)：117．
[22] Watanabe I，Tani S，Nagao K，et al. Regulation of arginine vasopressin in the humanheart[J]．Circ J，2005，69(11)：1401-1404．
[23] Preibisz JJ, Sealey JE, Laragh JH et al. Plasma and platelet vasopressin in essentialhypertension and congestive heart failure[J]. Hypertension,1983;5:1129-38.
[24] Morgenthaler NG, Struck J, Alonso C, et a1. Assay for the measurement of copeptin,astable peptide derived from the precursor of vasopressin. Clin Chem,2006,52:112-119.
[25] Fenske W，Stork S，Blechschmidt A，et al. Copeptin in the differential diagnosis ofhyponatremia[J]．J Clin Endocrinol Metab，2009，94(1)：123-129．
[26] Nigro N，Müller B，Morgenthaler N，et al. The use of copeptin，the stable peptideof the vasopressin precursor，in the differential diagnosis of sodium imbalance inpatients with acute diseases[J]．Swiss Med Wkly，20l1，141：w13270．
[27] Nagy G, Mulchahey JJ, Smyth DG, et al.The glycopeptides moiety ofvasopressin-neurophysin precursor is neurohypophysial prolactin releasing factor[J].Biochem Biophys Res Commun,1988,151:524-529.
[28] Barat C, Simpson L, Breslow E. Properties of human vasopressin precursorconstructs: Inefficient monomer folding in the absence of copeptin as a potentialcontributor to diabetes insipidus[J]. Biochemistry,2004,43:8191-8203.
[29] Katan M, Morgenthaler NG, Dixit KC, et a1. Anterior and posterior pituitary functiontesting with simultaneous insulin tolerance test and a novel copeptin assay[J]. J ClinEndocrinol Metab,2007,92(7):2640-3.
[30] Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from thevasopressin precursor, is elevated in serum of sepsis patients. Peptides,2005,26:2500-2504.
[31] Chenevier-Gobeaux C, Freund Y, C1aessens Y E, et a1. Copeptin for rapid rule out ofacute myocardial infartion in emergency department[J]．Inl J Cardiol，2011，Nov18．
[32] De Marchis GM，Katan M，Weck A，et al. Copeptin adds prognostic information afterischemic stroke:Results from the CoRisk study[J]. Neurology，2013，80(14):127812-86.
[33] Boeck L, Eggimann，P, Smyrnios N, et a1. The sequential organ failure assessmentscore and copeptin for predicting survival in ventilator-associated pneumonia[J]．JCrit Care,2012,27(5):523.e1-9
[34] Khan SQ，Dhillon OS，O’Brien RJ，et a1．C-terminal provasopressin(copeptin)asa novel and prognostic marker in acute myocardial infarction：Leicester AcuteMyocardial Infarction Peptide(LAMP)study[J]．Circulation，2007，115(16)：2103-2110．
[35] T lg R, Witt M，Schwarz B，et a1．Comparison of carvedilol and metoprolol inpatients with acute myocardial infarction undergoing primary coronaryintervention--the PASSAT Study[J]．Clin Res Cardiol．2006，95(1)：31-41．
[36] Fukuzawa J, Haneda T, Kikuchi K. Arginine vasopressin increases the rate of proteinsynthesis in isolated perfused adult rat heart via the V1receptor[J]. Mol CellBiochem.1999,195(1-2):93-98．
[37] Chai SB, Hui YM, Li XM, et a1. Plasma levels of copeptin in patients with coronaryheart disease[J]. Heart Vessels,2009,24(2):79-83.
[38] M ckel M, Danne O, Müller R, et al.Development of an optimized multimarkerstrategy for early risk assessment of patients with acute coronary syndromes[J].ClinChim Acta,2008,393:103-109.
[39] Dieplinger B, Gegenhuber A, Haltmayer M, et al. Evaluation of novel biomarkers forthe diagnosis of acute destabilised heart failure in patients with shortness ofbreath[J]．Heart,2009,95(18):1508-1513．
[40] Reichlin T, Hochholzer W, Stelzig C, et a1．Incremental value of copeptin for rapidrule out of acute myocardial infarction[J]．J Am Coil Cardiol,2009,54(1)：60-68．
[41]王晓艳，杨侃，孙明等．脑钠肽、和肽素和高敏C反应蛋白与急性冠状动脉综合征的相关性[J]．中国动脉硬化杂志，2009，17（3）：229-231．
[42]祝烨．慢性心力衰竭治疗进展．现代临床医学．2007，33(2)：148-150.
[43]治尉．精氨酸血管加压素与心力衰竭研究的进展[J]．心血管病学进展.2009,30(1)：95-99．
[44] Stoiser B，M rtl D，Hülsmann M，et al．Copeptin，a fragment of the vasopressinprecursor, as a novel predictor of outcome in heart failure[J]．Eur JClin Invest．2006,36(11)：771-778．
[45] Gegenhuber A．Struck J，Dieplinger B，et a1．Comparative evaluation of B-typenatriuretic peptide, Mid-regional pro-A-type natriuretic peptide． Mid-regionalpro-adrenomedullin, and copeptin to predict1-year mortality in patients with acutedestabilized heart failure[J]．J Card Fail，2007，13(1):42-49.
[46] Neuhold S, Huelsmann M，Strunk G, et a1. Comparison of copeptin，B-typenatriuretic peptide，and amino-terminal pro-B-type natriuretic peptide in patients withchronic heart failure：prediction of death at different stages of the disease[J]．J AmCoil Cardiol，2008，52(4):266-272.
[47] Tang WH，Flancis GS，Morrow DA，et aI．National academy of clinical biochemistrylaboratory medicine practice guidelines： clinical utilization of cardiac biomarkertesting in heart failure[J]．Circulation，2007，116(5)：99-109．
[48] Kelly D, Squire IB, Khan SQ, et a1. C-terminal provasopressin(copeptin)isassociated with left ventricular dysfunction, remodeling, and clinical heart failure insurvivors of myocardial infarction[J]. J Card Fail,2008,14(9):739-745.
[49] Voors AA, von Haehling S, Anker SD, et a1. C-terminal pro-vasopressin (copeptin)isa strong prognostic marker in patients with heart failure after an acute myocardialinfarction results from the OPTIMAAL study[J1．Eur Heart J，2009，30(10)：1187-1194．
[50] Alvarez-Sabin J，Delgado P，Abilleira S，et a1．Temporal profile of matrixmetallopromirmes and their inhibitors after spontaneous intracerebral hemorrhage：relationship to clinical and radiological outcome．Stroke,2004,35：1316-1322．
[51] Ferro JM. Update on intracerebral haemorrhage [J]. J Neurol,2006,253(8):985-999.
[52] Delgado P, Alvarez Sabin J, Montaner J. Biological markers in spontaneousintracerebral hemorrhage. Neurologia,2007,22:448-455.
[53] Zweifel C，Katan M，Schuetz P，et a1．Copeptin is associated with mortality andoutcome in patients with acute intracerebral hemorrhage．BMC Neurol，2010,10:34.
[54] Fassbender K, Schmidt R, Mossner R, et a1． Pattern of activation of thehypothalamic-pituitary-adrenal axis in acute stroke．Relation to acute confusionalstate，extent of brain damage, and clinical outcome．Stroke．1994．25：l105-l108．
[55] Slowik A, Turaj W，Pankiewicz J，et a1．Hypercortisolemia in acute stroke is relatedto the inflammatory respone．J Neurol Sci，2002，196：27-32．
[56] Volpi S， Rabadm-Diehl C， Aguilera G． Vasopressinersic regulation of thehypothalamic pituitary adrehal axis and stress adaptation．Stress,2004，7：75-83．
[57] Sapolsky RM．Pulsinelli WA．Glucocorticoids potentiate ischemic injury to neurons：therapeutic implicatiom．Science，1985，229：1397-1400．
[58] Smith-Swintosky VL, Pettigrew LC, Sapolsky RM, et al. Metyrapone, an inhibitor ofglucocorticoid production, reduces brain injury induced by focal and global ischemiaand seizures. J Cereb Blood Flow Metab,1996,16:585-598
[59] Potocki M，Breidthardt T，Mueller A，et a1．Copeptin and risk stralification inpatients with acute dyspnea [J]．Criti Care，20l0，14(6)：R213．
[60] Stolz D，Christ-Crain M，Morgenthaler NG，et al. Copeptin，C-reaccive protein，and procalcitonin as prognostic biomarkers in acute exacerbation of COPD[J].Chest，2007，13l(4)：1058-1067．
[61] Boeck L，Eggimann P，Smyrnios N，et a1．The sequential organ failure assessmentscore and copeptin for predicting survival in ventilator-associated pneumonia[J]．JCrit Care，20l2，27(5)：523．
[62] Müller B，Morgenthaler N，stolz D，el al Circulating levels of copeptin，a novelbiomarker，in lower respiratory tract infections[J]．Eur J Clin Invest，2007，37(2)：145-152．
[63] Saleem U，Khaleghi M，Morgenthaler NG，et a1．Plasma carboxy-terminalprovasopressin (copeptin)：a novel marker of insulin resistance and metabolicsyndrome[J]．J Clin Endocrinol Metab，2009．94(7)：2558-2564．
[64] Enhorning S，Wang TJ，Nilsson PM，et a1．Plasma copeptin and the risk of diabetesmellitus[J]．Circulation，2010，121(19)：2102-2108．
[65] Oghlakian G，Klapholz M．Vasopressin and vasopressin receptor antagonisls in heartfailure[J]．Cardiol Rev，2009，17(1)：10-15．
[66] Jochberger S, Morgenthaler NG, Mayr VD, et a1. Copeptin and arrginine vasopressinconcentrations in critically ill patients[J]．J Clin Endocrinol Melab,2006,91(11)：4381-4386.
[67] Jochberger S，Luckner G，Mayr VD，et a1．Course of vasopressin and copeptinplasma concentrations in a patient with severe septic shock[J]．Anaesth IntensiveCare,2006,34(4)：498-500.
[68]肖洋,张基刚,柴三葆.多种疾病患者血浆copeptin测定[J].放射免疫学杂志,2008,21(2)：97-100.
[69] Benzing J，Wellmann S，Achini F，et al. P1asma copeptin in preterm infants：a highlysensitive marker of fetal and neonatal stress[J]．J Clin Endocrinol Metab，2011，96(6)：982-985．
[70] Müller B, Morgenthaler N, Christ-Crain M, et a1. Circulating levels of copeptin, anovel biomarker, in lower respiratory tract infections[J]．Eur J Clin Invest，2007，37(2)：145-152．
[71] Szinnai G，Morgenthaler NG，Berneis K，et a1．Changes in plasma copeptin，thec-terminal portion of arginine vasopressin during water deprivation and excess inhealthy subjects[J]. J clin Endocrinol Metab，2007，92(10)：3973-3978．
[72] Morgenthaler NG，Müller B，Struck J．et a1．Copetin，a stable peptide of the argininevasopressin precursor, is elevated inhemorrhagic and septic shock[J]．Shock，2007，28(2):219-26.
[73] Wellmann S，Benzing J，Cippa G，et al. High copeptin concentrations in umbilicalcord blood after vaginal delivery and birth acidosis[J]．J Clin Endocrinol Metab，2010，95(11)：5091-5096．
[74] Morgenthaler NG，Struck J，Jochberger S，et a1．Copeptin：clinical use of a newbiomarker[J].Trends Endocrinol Metab，2008，19(2)：43-49.
[75] Katan M，Morgenthaler N，Widmer I，et a1．Copeptin，a stable peptide delived fromthe vasopressin precursor， correlates with the individual stress level[J].NeuroEndocrinol Lett，2008，29(3)：341-346.
[76] Meijer E，Bakker SJ，Halbesma N，et a1．Copeptin，a surrogate marker ofvasopressin，is associated with microalbuminuria in a large population cohort[J]．Kidney Int，20l0，77(1)：29-36．
[77] Dunser MW，Schmittinger CA，Torgersen C． Copeptiln and the transplantedkidney：friends or foes?[J]. Transplantation，2009，88(4)：455-456．
[78] Liebetrau C，Nef H，Szardien S，et al. Release kinetics of copeptin in patientsundergoing transcoronary ablation of septal hypertrophy[J]. Clin Chem，2013，59(3):566-569.
[79]张林峰，杨军，武阳丰等．我国人群中缺血性和出血性脑卒中发病的相对比例．中华内科杂志[J]．2003，42：94-97.
[80]饶明俐．中国脑血管病防治指南[M]．北京：人民卫生出版社，2007：1-24．
[81] Zhou H，Wang YJ，Wang SX，et a1．TOAST subtyping of acute ischemicstroke[J]．Zhonghua Nei Ke Za Zhi．2004，43(7):495-498.
[82] Adams HP Jr，Bendixen BH，Kappelle LJ，et a1．Classification of subtype of acuteischemic stroke.Definition for use in a multicenter clinical trial．TQAST．Trial of Org10172in Acute Stroke Treatment．Stroke,1993,24(1)：35-41．
[83] Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in theterritory of a symptomatic intracranial arterial stenosis Circulation [J].2006,113:555-63.
[84] Higashida RT, Meyers PM, Connors JJ, et al. Intracranial angioplasty and stenting forcerebral atherosclerosis: a position statement of the American Society ofInterventional and Therapeutic Neuroradiology, Society of Interventional Radiology,and the American Society of Neuroradiology[J]. J Vasc Interv Radiol.2005,16:1281-1285
[85]王桂红,王拥军,姜卫剑等.缺血性脑卒中患者脑动脉狭窄的分布及特征[J].中华老年心脑血管病杂志.2003,5:315-317
[86] Lee SJ, Cho SJ, Moon HS, et al. Combined extracranial and intracranialatherosclerosis in Korean patients[J].Arch Neurol.2003,60:1561-1564.
[87] Arenillas JF, Molina CA, Chacón P, et al.High lipoprotein (a), diabetes, and theextent of symptomatic intracranial atherosclerosis[J]. Neurology.2004,63:27-32.
[88] Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebralarteries: intracranial versus extracranial[J]. Neuroepidemiology.2003,22:37-40.
[89] Kuller LH. Epidemiology and prevention of stroke, now and in the future[J].Epidemiol Rev,2000,22:14-17
[90] Hu G, Sarti C, Jousilahti P, et al. The impact of history of hypertension and type2diabetes at baseline on the incidence of stroke and stroke mortality [J]. Stroke,2005,36:2538-2543
[91] Weikert C, Berger K,Heidemann C, et al. Joint effects of risk factors for stroke andtransient ischemic attack in a German population: the EPIC Potsdam Study[J].Neurology,2007,254:315-21
[92] Vivancos-Mora J, Gil-Nunez AC. Lipids and stroke: the opportunity oflipid-lowering treatment[J]. Cerebrovasc Dis,2005,20:53-67.
[93] Pinto A, Tuttolomondo A, Di Raimondo D, et al.Cerebrovascular risk factors andclinical classification of strokes[J].Semin Vasc Med,2004,4:287-303.
[94] Tanizaki Y, Kiyohara Y, Kato I，et a1．Incidence and risk factors for subtypes ofcerebral infarction in a general population：the Hisayama study[J]．Stroke,2000,31(11)：2616-2622．
[95] Syed NA，Khealani BA，Ali S,et a1．Ischemic stroke subtypes in Pakistan：the AgaKhan University Stroke Data Bank[J]．J Pak Med Assoc,2003，53(12)：584．
[96] Lovett JK,Coull AJ，Rothwell PM．Early risk of recurrence by subtype of ischemicstroke in population-based incidence studies[J]．Neurology,2004，62(4)：569-573．
[97] Bamford J，Sandercock P，Dennis M，et a1．Classification and natural history ofclinically identifiable subtypes of cerebral infarction[J]. Lancet,1991,337:1521-1526.
[98] Mead GE，O’Neill PA，Farrell JL, et a1．Does the Oxfordshire Commtmity Strokeproject classification predict the site of cerebral infarction?[J]. CerebrovascularDiseases,1996，6suppl2：155．
[99] Mead GE，Lewis SC，Wardlaw JM，et a1．How well does the Oxfordshire ofCommunity Stroke Project classification predict the site and size the infarct on brainimaging?[J]. J Neurol Neurosurg Psychiatry,2000，68：558-562．
[100] Mead GE, Wantlaw JM, Dennis MS, et al. Relationship between pattern ofintraeranial artery abnormalities on transcranial doppler and Oxfordshire CommunityStroke Project clinical classification of ischemic stroke[J]. Stroke,2000,31(3):714-719.
[101] Stum JW, Dewey HM, Donnan GA, et al. Handicap after stroke: how does it relate todisability, perception of recovery, and stroke subtype?: the north North EastMelbourne Stroke Incidence Study(NEMESIS)[J]．Stroke,2002，33：762-768．
[102] Kobayashi A, Wardlaw JM, Lindley RI, et al. Oxfordshire community stroke projectclinical stroke syndrome and appearances of tissue and vascular lesion onpretreatment CT in hyperacute ischemic stroke among the first510patients in theThird International Stroke Trial(IST-3)[J]. Stroke,2009,40(3):743-748.
[103] Hallstrom B, Norrving B, Lindgren A. Stroke in lund-orup, Sweden: improvedlong-term survival among elderly stroke patients[J]. Stroke,2002,33(6):1624-1629
[104] Staals J，Van Raak L，Hilton A，et a1．Differences in long-term survival in twolacunar stroke types：a15-year follow-up study in782cerebral infarct patients[J]．Cerebrovasc Dis,2008，25(1-2)：26-31．
[105] Feuerstein GZ, LiuT, BaroneFC. Cytokines, inflammation, and brain injure: Role oftumor necrosis factor-alpha. Cerebrovase brain Metab Rev,1994,6(4):341-360.
[106] Arvin B, Neville LF, Barone PC, et al. The role of inflannation and cytokines in braininjury. Neurosci Biobehave Rev,1996,20(33):445-452.
[107] Kubes P, Grisham MB, Barromen JA, et al. Leukocyte-induced vascular proteinleakage in Cat meseniery. Am J Physiol,1991,261: HI827-879.
[108] Jerome SN, Akinmetsu T, Korthuis RJ. Leukoeyte adhesion, edema, anddevelopment of postisehemic capillary no-refiow. Am JP hysiol,1994,267:H1329-336.
[109] Miyashita K, Abe H, Nakajima T, et al. Glutamate release in the gerbil hippocampusafter middle cerebral artery oeclusion. Neuroreport,1994,5:945-948.
[110] Osuga H, Hakin AM. Relationship between estracellular glutamate concentration andvoltge sensitive caleium channelfunction in fieal ischemia in the rat. J Cereb BloodFlow Metab,1996,16629-636.
[111] Fujiwara N, Abe T, Endoh H, et al. Changes in intraeellrllar pH of hippocampal slicesresponding tohypoxia and/or glueose depletion. Brain Res,1992,572:335-342.
[112] Siesjo BK. PathoPhysiology and treatment of foealeerebral isehemic. PartⅡ,meehanisms of damage and treatment. J Nerrosurg,1992,77:337-342.
[113] Wood NI, Barone Pc, Benham CD, et al. The effects of SB206284A, a novelneuronal caleium channel antagonist, in models of cerebral ischemia. J Cereb BloodFlow Mctab,1997,17(4):421-429.
[114] Bedsen DE. Neural apoptosis.Ann Neurol,1995,38:839-851.
[115] Koh JY, Suh Sw, Gwag BJ, et al. The role of zinic in selective neuronal deathfollowing transient global isehemia. Seienee,1996,272:1013-1016.
[116] Nagayama M, Niwa K, Nagayama T, et al. The cyelooxygenase2inhibitor NS-398ameliorates ischemic brain injure in wild-type mice but not in mice with deletion ofthe indueible nitric oxide synthase gene. J Cereb Blood Flow Metab,1999,19(11):1212-1219.
[117] Holroyol-Ledue JM，Kapral MK Austin PC，et a1．Sex difference and similarities inthe management and outcome of stroke patients[J]．Stroke．2000，31：1833-1837．
[118] Lobo RA．Menopause and stroke and the effects of hormonal therapy [J]．Climacteric,2007,12：27-31．
[119] Homer S，Niederkom K Schnabl S，et a1．Gender aspects of Ischemic stroke．Ananalysis of the Austrian Stroke-Unit Registry[J]．Wien Med Wochenschr．2008，158(15-16)：446-452．
[120] Saini M，Shuaib A．Stroke in women[J]．Recent Pat Cardiovasc Drag Discov,2008,3(3)：209-221．
[121] Billeci AM，Paciaroni M，Caso V，et a1．Hormone replacement therapy andStroke[J]．Curt Vase Pharmacol,20086(2)：112-123．
[122] Olsen TS，Dehlendorff C，Andersen KK．Gender differences in stroke mortalityrate[J]．Neuroepidemiology．2007，29(3-4)：218-225．
[123] Lai SM，Duncan PW，Dew P，et a1．Sex differences in stroke recovery [J]．PrevChronic Dis,2005,2(3): A13.
[124] Robinsion-Smith G, Johnston MV, Alien J，et a1．Self-care self-effieaey, quality oflife, and depression after stroke[J]. Arch Phy Rehabil,2000,81:460-464.
[125] De Jong G, van Raak L, Kessels F, et al. Stroke subtype and mortality, a follow-upstudy in998patients with a first cerebral infarct[J]. J Clin Epidemiol,2003,56：262-268.
[126] Hart CL, Hole DJ, Smith GD et al.comparison of risk factors for stroke incidenceand stroke mortality in20years or follow up in men and women in the Renfrewpaisley study in Scotland[J]. Stroke,2000,31(8):1893-1896.
[127] Minn YK, Cho SJ, Kim SG, et al. Long-term outcomes of acute ischemic stroke inpatients ages80years and older[J]. Yonsei Med J,2008,49(3):400-404.
[128] Morales-Ortiz A，Jimenez-Pascual M. Fever of central origin during stroke [J]．RevNeurol．2001,32(12)：1111-1114．
[129] Greer DM，Funk SE，Reaven NL，et a1．Impact of fever on outcome in patients withstroke and neurologic injury：a comprehensive meta-analysis[J]．Stroke,2008,39(11)：3029-3035．
[130] Fernandez A, Schmidt JM, Claassen J, et al. Fever after subarachnoid hemorrhage:risk factors and impact on outcome[J]. Neurology,2007,68(13):973-974.
[131] Kammersagaard LP, Jorgensen HS. Admission body temperature predicts long-termmortality after acute stroke[J]. Stroke,2002,33(7):1759-1762.
[132] De Georgia MA，Krieger DW，Abou-Chebl A，et a1．Cooling for acute ischemicbrain damage(COOL AID)： a feasibility trial of endovascular cooling [J].Neurology．2004，63：312-317．
[133] Olsen TS, Weber UJ, Kammersgaard LP. Therapeutic hypothermia for acute stroke[J].Lancet Neurol,2003,2(7):410-416.
[134]彩霞，周钦，黄载文．亚低温、低温治疗重症脑卒中疗效观察[J]．中西医结合心脑血管病杂志,2007，5(9)：898-899．
[135] Abboud H，Labreuche J，Plouin F, et a1．Hi．gh blood pressure in early acute stroke：a sign of a poor outcome[J].J Hypertens,2006,24(2)：381-386．
[136] Yong M，Kaste M．Association of characteristics of blood pressure profiles andstroke outcomes in the ECASS-II trial[J]．Stroke,2008，39(2)：366-372．
[137] Willmot M，Leonardi-Bee J，Bath PMW．High blood pressure in acute stroke andsubsequent outcome[J]．A Systematic Review．Hypertension,2004，43：18-24．
[138] Leonardi-Bee J, Bath PMW, Phillips SJ, et a1．Blood pressure and clinical outcomein the International Stroke Trial[J]．Stroke,2002,33：1315-1320．
[139] Cassidy E，O’Connor R,0’Keane V. Prevalence of post-stroke depression in an Irishsample and its relationship with disability and outcome following inpatientrehabilitation[J]．Disabil Rehabil,2004,26(2)：71-77．
[140]龙洁，刘永珍．卒中及抑郁状的发生及相关因素研究[J]．中华神经科杂志,2001，34(9)：145．
[141]温萍，李旭方，刘满芬等.汕头地区脑卒中后遗症患者抑郁症发病率及其对生活质量的影响[J].华北煤炭医学院学报，2008,10（4）：451-452.
[142]勾丽洁，许士奇，刘旭东等．脑卒中后抑郁的发生率及其对运动功能恢复的影响[J].承德医学院学报，2008,25（3）：251-253.
[143] Berg A，Palomaki H，Lehtihalmes M，et a1．Poststroke depression：an18-monthfollow-up[J]．Stroke．2003，34(1)：138-143．
[144] Saxena SK, Ng TP, Koh G, et al. Is improvement in impaired cognition anddepressive symptoms in post-stroke patients associated with recovery in activities ofdaily living?[J]. J Stroke Cerebrovasc Dis,2004,13(5):220-227.
[145]繆鸿石，朱镛连.急期性脑卒中的康复评定和治疗[M].北京：华夏出版社，1996:141-144.
[146] Elkind MS, Cheng J, Rundek T, et al. Leukocyte count predicts outcome afterischemic stroke: the Northern Manhattan Stroke Study[J]. J Stroke Cerebrovasc Dis,2004,13(5):220-227
[147]韩俊英，夏颖华.血清白细胞介素-6对缺血性脑卒中患者预后的影响[J].中国老年保健医学，2008,6（4）：14-16.
[148] Waje-Andreassen U，Kfftkenes J，Ulvestad E，et a1．IL-6：an early marker foroutcome in acute ischemic stroke[J]．Acta Neurol Scand．2005Jun，111(6)：360-365．
[149] Kazmierski RGuzik P，et al.Predictive value of white blood cell count on admissionfor in-hospital mortality in acute stroke patients． Clini[J]． NeurolNeurosurgery．2004，107(1)：38-43．
[150] Rallidis LS，Vikelis M，Panagiotakos DB，et a1．Inflammatory markers andin-hospital mortality in acute ischaemic stroke[J]．Atherosclerosis．2006,189(1)：193-197．
[151] Szczudlik A，Slowik A，Turaj W，et a1．Transient hyperglycemia in ischemia strokepatients[J]．J Neurol Sci．2001，189(1-2)：1005-1011．
[152] Els T，Klisch J，Orszagh M，et a1．Hyperglycemia in patient swith focal cerebralischemia after intravenous thrombolysis·influence on clinical outcome and infarctsize[J]．Cerebrovasc Dis．2002，13(2)：89-94．
[153] Garg R Chaudhuri A，Munschauer F，et a1．Hyperglycemia, insulin, a acute ischemicstroke：a mechanistic justification for atrial of insulin infusion therapy [J]．Stroke,2006，37(1):267-273.
[154]林亚新，周茵，关东威.应激性血糖增高对急性脑卒中预后影响的临床研究[J].中国老年学杂志，2005,25（6）：617-619.
[155] Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and prognosis of strokein nondiabetic and diabetic patient: systematic overview[J]. Stroke,2001,32:2426-2432.
[156]陈静.应激性血糖增高对急性脑卒中预后影响的临床研究[J].医学理论与实践,2008,21(5):538-539.
[157] Becker K. Intensive care unit management of the stroke patient[J]. Neurol clin,2000,18(2):439-545.
[158] Rudd AG, Hoffman A, Irwin P, et al. Stroke unit care and outcome: resuits from the2001National Sentinel Audit of Stroke(England Wales, and Northern Ireland)[J].Stroke,2005,36:103-106.
[159] Langhorne P, Dey P, Woodman M, et al. Is stroke unit care portable? A systematicreview of the clinical trials[J]. Age Ageing,2005,34:324-330.
[160]王拥军.卒中单元[M].北京：科学技术文献出版社，2004:5-33.
[161]饶明俐.中国脑血管病防治指南[M].北京：人民卫生出版社，2007：110-114.
[162] Evers SM, Struijs JN, Ament AJ, et al. International comparison of stroke coststudies[J]. Stroke,2004,351(51):1209-1215.
[163] Yoneda Y, Uehara T, Yamasakl H, et al. Hospital based study of the care and cost ofacute ischemic stroke in Japan[J]. Stroke,2003,34(3):718-724.
[164]石玲燕，金嵘，郑荣远等.温州地区脑卒中住院患者费用分析[J].中国公共卫生，2006，22（8）：1022-1023
[165]刘力生．中国高血压防治指南[M]．2005年修订版．北京：人民卫生出版社，2005：18．2l
[166]钱荣立．中国糖尿病防治指南[M]．北京：北京大学医学出版社，2004：12．16．
[167]叶任高，陆再英．内科学[M]．第6版．北京：人民卫生出版社，2004：821．831．
[168] Lee TH，Hsu WC，Chen CJ，et a1．Etiologic study of young ischemic stroke inTaiwan[J]．Stroke，2002，33：1950-1955．
[169] Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, et al. Copeptin: a novel,independent prognostic marker in patients with ischemic stroke. Ann Neurol,2009,66:799-808.
[170] Pullicino P, Nelson KF, Kendall BE, et al. Small deep infarcts diagnosed oncomputed tomography [J]. Neurology,1980,30:1090
[171] Bonita R BR. Modification of Rankin Scale: recovery of motor function after stroke.Stroke,1988,19:1497-500.
[172] Xuedon g Liu, Yali L v, Bo Wang, et al. Pr edict ion of fun ct ional out com e ofischem ic st roke pat ient s in northwest China. Clinical Neurology an d Neurosurgery,2007,109(4):571-577.
[173]张断荣,张文禹,林素君.31例脑卒中患者ADL能力评价与康复训练[J].中国康复,1995,10(4):17.
[174] Sanders DE. Measurment of infarct size using MRI predict s prognosis in middlecerebral art ery infarction [J]. Stroke,1995,26:2272.
[175] Johansson BB, Jadback G, Norrving B, et al. Evaluation of longterm functional statusin first-ever stroke patients in a difined population [J]. Scand J Rehabil Med.1992,26(suppl):105-14.
[176] Johnston SC．Clinical practice．Transient ischemic attack．N Engl J Med,2002,347:1687-1692．
[177] Whiteley W, Chong WL, Sengupta A, Sandercock P. Blood markers for the prognosisof ischemic stroke: a systematic review. Stroke,2009,40:380-389.
[178] Di Napoli M, Papa F, Bocola V. Prognostic infuence of increased C-reactive proteinand fbrinogen levels in ischemic stroke. Stroke,2001,32:133–8.
[179] Elkind MS, Tai W, Coates K, et al. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med,2006,166:2073–80.
[180] Shantikumar S, Grant PJ, Catto AJ, et al. Elevated C-reactive protein and long-termmortality after ischaemic stroke: relationship with markers of endothelial cell andplatelet activation. Stroke,2009,40:977-979.
[181] Whiteley W, Jackson C,Lewis S,et al. Inflammatory markers and poor outcomeafter stroke: a prospective cohort study and systematic review of interleukin-6. PlosMed2009,6:e1000145
[182] Kelly PJ, Morrow JD, Ning M, et al. Oxidative stress and matrix metalloproteinase-9in acute ischemic stroke. The Biomarker Evaluation for Antioxidant Therapies inStroke (BEAT-Stroke) study. Stroke,2008,39:100-104.
[183] Del Zoppo GJ, Levy DE, Wasiewski WW, et al. Hyperfbrinogenemia and functionaloutcome from acute ischemic stroke. Stroke,2009,40:1687-1691.
[184] Whiteley W, Rumley A, Sattar N, et al. POS11blood markers and poor outcome afteracute cerebrovascular disease: a prospective cohort study. J Neurol NeurosurgPsychiatry,2010,81: e70.
[185] Neidert S, Katan M, Schuetz P, et al. Anterior pituitary-axis hormones and outcomein acute ischemic stroke. J Intern Med,2011,269:420-432.
[186] Urwyler SA, Schuetz P, Fluri F, et al. Prognostic value of copeptin: one-year outcomein patients with acute stroke. Stroke,2010,41:1564-1567.
[187] Nickel CH, Bingisser R, Morgenthaler NG. The role of copeptin as a diagnostic andprognostic biomarker for risk stratification in the emergency department. BMC Med,2012,10:7.
[188] Meisel A, Meisel C, Harms H, Hartmann O, Ulm L. Predicting post-stroke infectionsand outcome with blood-based immune and stress markers. Cerebrovasc Dis,2012,33:580-588.
[189] De Marchis GM, Katan M, Weck A, et al. Copeptin and risk stratification in patientswith ischemic stroke and transient ischemic attack: The CoRisk Study. Int J Stroke,2012, doi:10.1111/j.1747-4949.2011.00762.x.
[190] Shuaib A, Xu Wang C, Yang T, Noor R. Effects of nonpeptide V(1) vasopressinreceptor antagonist SR-49059on infarction volume and recovery of function in afocal embolic stroke model. Stroke,2002,33:3033-3037.
[191] Rose CE Jr, Anderson RJ, Carey RM. Antidiuresis and vasopressin release withhypoxemia and hypercapnia in conscious dogs. Am J Physiol1984;247:R127-134.
[192] Jochberger S, Mayr VD, Luckner G, et al. Serum vasopressin concentrations incritically ill patients. Crit Care Med,2006,34:293-299.
[193] Armstead WM. Vasopressin-induced protein kinase C-dependent superoxidegeneration contributes to atp-sensitive potassium channel but not calcium-sensitivepotassium channel function impairment after brain injury. Stroke,2001,32:1408-1414.
[194] Vakili A, Kataoka H, Plesnila N. Role of arginine vasopressin V1and V2receptorsfor brain damage after transient focal cerebral ischemia. J Cereb Blood Flow Metab,2005,25:1012-1019.
[195] Kozniewska E, Gadamski R, Klapczynska K, et al. Morphological changes in thebrain during experimental hyponatremia. Do vasopressin and gender matter FoliaNeuropath,2008,46:165-170.
[196] Kozniewska E, Romaniuk K. Vasopressin in vascular regulation and waterhomeostasis in the brain. J Physiol Pharmacol,2008,59(Suppl8):109-116.
[197] Potocki M, Breidthardt T, Mueller A. Copeptin and risk stratification in patients withacute dyspnea. Critical Care,2010,14：213...