| Journal of Translational Medicine | |
| Comparison of acute versus convalescent stage high-sensitivity C-Reactive protein level in predicting clinical outcome after acute ischemic stroke and impact of erythropoietin | |
| Hon-Kan Yip3  Chun-Man Yuen1  Hung-Sheng Lin4  Yung-Lung Chen3  Sarah Chua3  Sheng-Ying Chung3  Steve Leu2  Han-Tan Chai3  Tzu-Hsien Tsai3  Kuo-Ho Yeh3  | |
| [1] Department of Neurosurgery; Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung. Taiwan;Center for translational research in biomedical science Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung. Taiwan;Division of cardiology Division of Cardiology, Department of Internal Medicine; Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung. Taiwan;Department of Neurology Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung. Taiwan | |
| 关键词: adverse clinical outcome; erythropoietin; high-sensitivity C-reactive protein; acute ischemic stroke; | |
| Others : 1207789 DOI : 10.1186/1479-5876-10-6 |
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| received in 2011-09-18, accepted in 2012-01-05, 发布年份 2012 | |
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【 摘 要 】
Background and Aim
Currently, no data on the optimal time point after acute ischemic stroke (IS) at which high-sensitivity C-reactive protein (hs-CRP) level is most predictive of unfavorable outcome. We tested the hypothesis that hs-CRP levels during both acute (48 h after IS) and convalescent (21 days after IS) phases are equally important in predicting 90-day clinical outcome after acute IS. We further evaluated the impact of erythropoietin (EPO), an anti-inflammatory agent, on level of hs-CRP after acute IS.
Methods
Totally 160 patients were prospectively randomized to receive either EPO therapy (group 1, n = 80) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or placebo (group 2, n = 80). Serum level of hs-CRP was determined using ELISA at 48 h and on day 21 after IS and once in 60 healthy volunteers.
Results
Serum level of hs-CRP was substantially higher in all patients with IS than in healthy controls at 48 h and day 21 after IS (all p < 0.001). Levels of hs-CRP did not differ between group 1 and 2 at 48 h and day 21 after IS (all p > 0.5). Multivariate analysis showed that hs-CRP levels (at 48 h and day 21) were independently predictive of 90-day major adverse neurological event (MANE) (defined as recurrent stroke, NIHSS≥8, or death) (all p < 0.03), whereas EPO therapy was independently predictive of reduced 90-day MANE (all p < 0.02).
Conclusion
EPO therapy which was independently predictive of freedom from 90-day MANE did not alter the crucial role of hs-CRP levels measured at 48 h and 21-day in predicting unfavorable clinical outcome after IS.
【 授权许可】
2012 Yeh et al; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
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| 20150530110100279.pdf | 801KB | ||
| Figure 5. | 25KB | Image | |
| Figure 4. | 28KB | Image | |
| Figure 3. | 25KB | Image | |
| Figure 2. | 26KB | Image | |
| Figure 1. | 39KB | Image |
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【 参考文献 】
- [1]Ross R: The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 1993, 362:801-809.
- [2]van der Wal AC, Becker AE, van der Loos CM, Das PK: Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994, (89):36-44.
- [3]Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med 1999, 340:115-126.
- [4]Yip HK, Sun CK, Chang LT, Wu CJ: Strong correlation between serum levels of inflammatory mediators and their distribution in infarct-related coronary artery. Circ J 2006, (70):838-845.
- [5]Yip HK, Wu CJ, Yang CH, Chang HW, Fang CY, Hung WC, Hang CL: Serial changes in circulating concentrations of soluble cd40 ligand and c-reactive protein in patients with unstable angina undergoing coronary stenting. Circ J 2005, (69):890-895.
- [6]Yip HK, Hang CL, Fang CY, Hsieh YK, Yang CH, Hung WC, Wu CJ: Level of high-sensitivity c-reactive protein is predictive of 30-day outcomes in patients with acute myocardial infarction undergoing primary coronary intervention. Chest 2005, (127):803-808.
- [7]Burke AP, Tracy RP, Kolodgie F, Malcom GT, Zieske A, Kutys R, Pestaner J, Smialek J, Virmani R: Elevated c-reactive protein values and atherosclerosis in sudden coronary death: Association with different pathologies. Circulation 2002, (105):2019-2023.
- [8]Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med 2008, 359:2195-2207.
- [9]Makita S, Nakamura M, Satoh K, Tanaka F, Onoda T, Kawamura K, Ohsawa M, Tanno K, Itai K, Sakata K, Okayama A, Terayama Y, Yoshida Y, Ogawa A: Serum c-reactive protein levels can be used to predict future ischemic stroke and mortality in japanese men from the general population. Atherosclerosis 2009, 204:234-238.
- [10]Everett BM, Glynn RJ, MacFadyen JG, Ridker PM: Rosuvastatin in the prevention of stroke among men and women with elevated levels of c-reactive protein: Justification for the use of statins in prevention: An intervention trial evaluating rosuvastatin (jupiter). Circulation 2010, 121:143-150.
- [11]Jiang S, Bao Y, Hou X, Fang Q, Wang C, Pan J, Zuo Y, Zhong W, Xiang K, Jia W: Serum c-reactive protein and risk of cardiovascular events in middle-aged and older chinese population. Am J Cardiol 2009, 103:1727-1731.
- [12]Morrone G, Ciliberto G, Oliviero S, Arcone R, Dente L, Content J, Cortese R: Recombinant interleukin 6 regulates the transcriptional activation of a set of human acute phase genes. J Biol Chem 1988, 263:12554-12558.
- [13]Le JM, Vilcek J: Interleukin 6: A multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest 1989, (61):588-602.
- [14]Youn CS, Choi SP, Kim SH, Oh SH, Jeong WJ, Kim HJ, Park KN: Serum highly selective c-reactive protein concentration is associated with the volume of ischemic tissue in acute ischemic stroke. Am J Emerg Med 2012, (30):124-128.
- [15]Camerlingo M, Valente L, Tognozzi M, Beretta GL, Moschini L, Cesana BM: C-reactive protein levels in the first three hours after acute cerebral infarction. Int J Neurosci 2011, (121):65-68.
- [16]McGee KA, Baumann NA: "Procalcitonin: Clinical Utility in Diagnosing Sepsis". Clinical Laboratory News 2009, 35:1-8.
- [17]Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M: Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 2003, (100):4802-4806.
- [18]Hirata A, Minamino T, Asanuma H, Fujita M, Wakeno M, Myoishi M, Tsukamoto O, Okada K, Koyama H, Komamura K, Takashima S, Shinozaki Y, Mori H, Shiraga M, Kitakaze M, Hori M: Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs. J Am Coll Cardiol 2006, (48):176-184.
- [19]Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, Itri LM, Cerami A: Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 2000, (97):10526-10531.
- [20]Villa P, Bigini P, Mennini T, Agnello D, Laragione T, Cagnotto A, Viviani B, Marinovich M, Cerami A, Coleman TR, Brines M, Ghezzi P: Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 2003, 198:971-975.
- [21]van der Meer P, Voors AA, Lipsic E, van Gilst WH, van Veldhuisen DJ: Erythropoietin in cardiovascular diseases. Eur Heart J 2004, (25):285-291.
- [22]Lipsic E, van der Meer P, Henning RH, Suurmeijer AJ, Boddeus KM, van Veldhuisen DJ, van Gilst WH, Schoemaker RG: Timing of erythropoietin treatment for cardioprotection in ischemia/reperfusion. J Cardiovasc Pharmacol 2004, (44):473-479.
- [23]Lin JS, Chen YS, Chiang HS, Ma MC: Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury: Role of erythropoietin on progenitor cell mobilization. J Physiol 2008, (586):5757-5769.
- [24]Yip HK, Tsai TH, Lin HS, Chen SF, Sun CK, Leu S, Yuen CM, Tan TY, Lan MY, Liou CW, Lu CH, Chang WN: Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke. Crit Care 2011, 15:R40. BioMed Central Full Text
- [25]Goldstein LB, Bertels C, Davis JN: Interrater reliability of the nih stroke scale. Arch Neurol 1989, (46):660-662.
- [26]Muir KW, Weir CJ, Murray GD, Povey C, Lees KR: Comparison of neurological scales and scoring systems for acute stroke prognosis. Stroke 1996, (27):1817-1820.
- [27]Mahoney FI, Barthel DW: Functional Evaluation. The Barthel Index. Maryland state medical journal 1965, 14:61-65.
- [28]van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J: Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988, 19:604-607.
- [29]Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R: Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997, 336:1276-1282.
- [30]Ishigaki Y, Oka Y, Katagiri H: Circulating oxidized ldl: A biomarker and a pathogenic factor. Curr Opin Lipidol 2009, (20):363-369.
- [31]Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR: C-reactive protein and outcome after ischemic stroke. Stroke 1999, (30):981-985.
- [32]Idicula TT, Brogger J, Naess H, Waje-Andreassen U, Thomassen L: Admission c-reactive protein after acute ischemic stroke is associated with stroke severity and mortality: The 'bergen stroke study'. BMC Neurol 2009, 9:18. BioMed Central Full Text
- [33]Di Napoli M, Papa F, Bocola V: C-reactive protein in ischemic stroke: An independent prognostic factor. Stroke 2001, (32):917-924.
- [34]Winbeck K, Poppert H, Etgen T, Conrad B, Sander D: Prognostic relevance of early serial C-reactive protein measurements after first ischemic stroke. Stroke 2002, 33:2459-64.
- [35]Song IU, Kim YD, Kim JS, Lee KS, Chung SW: Can high-sensitivity C-reactive protein and plasma homocysteine levels independently predict the prognosis of patients with functional disability after first-ever ischemic stroke? Eur Neurol 2010, 64:304-10.
- [36]Tseng MY, Hutchinson PJ, Richards HK, Czosnyka M, Pickard JD, Erber WN, Brown S, Kirkpatrick PJ: Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, double-blind, placebo-controlled trial. Clinical article. Journal of neurosurgery 2009, 111:171-180.
- [37]Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F: Erythropoietin therapy for acute stroke is both safe and beneficial. Molecular medicine 2002, 8:495-505.
- [38]Yuen CM, Leu S, Lee FY, Yen CH, Lin YC, Chua S, Chung SY, Chai HT, Sheu JJ, Ko SF, Sun CK, Yip HK: Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat. J Investig Med 2010, (58):893-904.
- [39]Spence JD: Treating hypertension in acute ischemic stroke. Hypertension 2009, (54):702-703.
- [40]Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA: Blood pressure and clinical outcomes in the international stroke trial. Stroke 2002, (33):1315-1320.
- [41]Sare GM, Ali M, Shuaib A, Bath PM: Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA collaboration. Stroke 2009, 40:2098-2103.
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