血清Cystatin C在急性心肌梗死病人中的变化
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摘要
背景：弹性蛋白溶解的半胱氨酸蛋白酶、天冬氨酸蛋白酶等组织蛋白酶的过度表达，参与动脉粥样硬化的形成。蛋白酶溶解活性和抗蛋白酶溶解活性比例失衡在血管壁重建和动脉粥样硬化斑块稳定性中发挥重要作用。在血清中Cystatin C是最丰富的蛋白酶抑制剂。有研究发现，在主动脉瘤患者血清Cystatin C水平较低，且通过超声探测发现早期动脉瘤患者血清Cystatin C水平与动脉瘤病变扩展呈负相关。也有研究发现在动脉粥样硬化和动脉瘤病变组织中Cystatin C表达明显低下。
目的：探讨血清Cystatin C在急性心肌梗死病人发病不同时期的浓度变化及作为早期诊断指标和预测斑块稳定性的临床价值。
方法：采用速率散射比浊法对发病48小时内及1周后的急性心肌梗死病人、不稳定心绞痛患者和对照组的血清Cystatin C水平进行测定。
结果：血清Cystatin C在急性心肌梗死组发病48小时内与对照组相比有所下降，但没有达到统计学意义(P=0.28)。然而当用肌酐校正后即Cystatin C／Creatinine进行计算时，差别明显，达到统计学意义(P=0.003)。同一组急性心肌梗死患者在发病1周后与发病48小时内相比，血清Cystatin C水平明显升高(P=0.04)。在直线相关分析中，血清Cystatin C水平与年龄、肌酐呈正相关。在多元逐步回归分析时，年龄与肌酐仍与血清Cystatin C水平独立相关，Multiple R=0.413。
结论：血清Cystatin C水平在急性心肌梗死发病早期明显下降。是否血清Cystatin C水平的下降先于急性心肌梗死发病已经存在，且能触发冠状动脉粥样斑块的破裂，或是血清Cystatin C水平的下降仅代表一种负向的急性期反应，目前仍然不清楚。提示血清Cystatin C浓度变化在一定程度上可作为急性心肌梗死早期诊断的参考指标。
Background: Overexpression of elastolytic cysteine and aspartic proteases, known as cathepsins, is implicated in atherogenesis. Imbalance of proteolytic and antiproteolytic levels plays a important role in vascular wall remodeling and the stability of the atherosclerosis plaque. Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients' with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. Low intralesion Cystatin C expression have also been found in patients with established aortic aneurysm and atherosclerosis.
Objective: To explore the changes of serum Cystatin C and its value as a sign of early diagnosis and predicting stability of atherosclerotic plaque in patients with acute myocardial infarction.
Methods: In this study, serum levels of Cystatin C have been investigated in patients with acute myocardial infarction, unstable angina and controls.
Results: Cystatin C was lower in acute myocardial infarction (AMI) patients during onset but the difference did not reach statistical significance compared to controls(P=0.28). Nevertheless, when Cystatin C/Creatinine ratio was considered, significantly lower values were found in acute AMI patients(P=0.003). Cystatin C plasma levels increased in the same AMI patients in a week after the acute event(P=0.04). At univariate analyses, Cystatin C levels were positively correlated with age and creatinine. The same variables were also independently correlated with Cystatin C levels in a multiple-regression analysis with a multiple R=0.413.
目的：探讨血清Cystatin C在急性心肌梗死病人发病不同时期的浓度变化及作为早期诊断指标和预测斑块稳定性的临床价值。
方法：采用速率散射比浊法对发病48小时内及1周后的急性心肌梗死病人、不稳定心绞痛患者和对照组的血清Cystatin C水平进行测定。
结果：血清Cystatin C在急性心肌梗死组发病48小时内与对照组相比有所下降，但没有达到统计学意义(P=0.28)。然而当用肌酐校正后即Cystatin C／Creatinine进行计算时，差别明显，达到统计学意义(P=0.003)。同一组急性心肌梗死患者在发病1周后与发病48小时内相比，血清Cystatin C水平明显升高(P=0.04)。在直线相关分析中，血清Cystatin C水平与年龄、肌酐呈正相关。在多元逐步回归分析时，年龄与肌酐仍与血清Cystatin C水平独立相关，Multiple R=0.413。
结论：血清Cystatin C水平在急性心肌梗死发病早期明显下降。是否血清Cystatin C水平的下降先于急性心肌梗死发病已经存在，且能触发冠状动脉粥样斑块的破裂，或是血清Cystatin C水平的下降仅代表一种负向的急性期反应，目前仍然不清楚。提示血清Cystatin C浓度变化在一定程度上可作为急性心肌梗死早期诊断的参考指标。
Background: Overexpression of elastolytic cysteine and aspartic proteases, known as cathepsins, is implicated in atherogenesis. Imbalance of proteolytic and antiproteolytic levels plays a important role in vascular wall remodeling and the stability of the atherosclerosis plaque. Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients' with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. Low intralesion Cystatin C expression have also been found in patients with established aortic aneurysm and atherosclerosis.
Objective: To explore the changes of serum Cystatin C and its value as a sign of early diagnosis and predicting stability of atherosclerotic plaque in patients with acute myocardial infarction.
Methods: In this study, serum levels of Cystatin C have been investigated in patients with acute myocardial infarction, unstable angina and controls.
Results: Cystatin C was lower in acute myocardial infarction (AMI) patients during onset but the difference did not reach statistical significance compared to controls(P=0.28). Nevertheless, when Cystatin C/Creatinine ratio was considered, significantly lower values were found in acute AMI patients(P=0.003). Cystatin C plasma levels increased in the same AMI patients in a week after the acute event(P=0.04). At univariate analyses, Cystatin C levels were positively correlated with age and creatinine. The same variables were also independently correlated with Cystatin C levels in a multiple-regression analysis with a multiple R=0.413.
引文
1. Libby p, Geng YJ, Aikawa M, et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol, 1996, 75:330-335
2. Libby P. Molecular bases of the acute coronary syndromes. Circulation, 1995, 91: 2844-2850
3. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res, 2002,90:251-262
4. Thompson RW, Parks WC. Role of matrix metalloproteinases in abdominal aortic aneurysm. Ann N YAcad Sci, 1996, 800:157-174
5. Rao SK, Reddy KV, Cohen JR. Role of serine proteases in aneurysm development. Ann N Y Acad Sci, 1996, 800:131-137
6. Sukhova GK, Shi GP, Simon DI, et al. Expression of elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest, 1998, 102:576-583
7. Shimizu-Tokiwa A, Kobata M, Io H, et al. Serum Cystatin C is a more sensitive marker of glomerular function than serum creatinine. Nephron, 2002, 92:224-226
8. Chapman HA, Reilly J J, Yee R, et al. Identification of Cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. Am Rev Respir Dis, 1990, 141:698-705
9. Warfel AH, Zucker-Franklin D, Frangione B, et al. Constitutive secretion of Cystatin C by monocytes and macrophages and its downregulation after stimulation. J Exp Med,1987,166:1912-17
10. Shi GP, Sukhova GK, Grubb A, et al. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest, 1999, 104(9):1191-1197
11. Lindholt JS, Erlandsen EJ, Henneberg EW. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg, 2001, 88(11):1472-1475
12. Randers E, Erlandsen EJ. Serum Cystatin C as an endogenous marker of the renal function. Clin Chem Lab Med, 1999, 37(4):389
13．黄亚，石娟娟，忻鼎广，等。血清半胱氨酸蛋白酶抑制物C：肾功能的敏感指标。上海医学检验杂志，2001，16(5)
14．裘晓蕙，钟光辉，陈巍，等。应用血清西司他汀浓度测定肾小球滤过率的相关研究。中华肾脏病杂志，2001，17(1)：35-3615. Parks WC. Who are the proteolytic culprits in vascular disease? J Clin Invest, 1999, 104(9): 1167-1168
16. Davide Noto, Angelo Baldassare Cefalu, Carlo Maria Barbagallo, et al. Cystatin C levels are decreased in acute myocardial infarction. Effect of Cystatin C G73A gene polymorphism on plasma levels. International Journal of Cardiology, 2005, 101:213-217
17. Pfohl M, Schreiber I, Liebich HM, et al. Upregulation of cholesterol synthesis after acute myocardial infarction—is cholesterol a positive acute phase reactant? Atherosclerosis, 1999,142(2):389-393
18. Wattanasuwan N, Khan IA, Gowda RM, et al. Effect of acute myocardial infarction on cholesterol ratios. Chest, 2001, 120(4): 1196-1199
19. Eriksson P, Deguchi H, Samnegard A, et al. Human evidence that the Cystatin C gene is implicated in focal progression of coronary artery disease. Arterioscler Thromb Vasc Biol, 2004, 24:551-557
20. Bengtsson E, To F, Grubb A, et al. Absence of the protease inhibitor Cystatin C in inflammatory cells results in larger plaque area in plaque regression of apoE-deficient mice. Atherosclerosis, 2005,180(1 ):45-53
21. Johnston N, Jernberg T, Lindahl B, et al. Biochemical indicators of cardiac and renal function in a healthy elderly population. Clinical Biochemistry, 2004, 37 (3):210-216
22. Luc G, Bard JM, Lesueur C, et al. Plasma Cystatin C and development of coronary heart disease: The PRIME Study. Atherosclerosis, 2006,185(2):375-380
23. Tomas J, Bertil L, Stefan J, et al. Cystatin C: a novel predictor of outcome in suspected or confirmed non-st-elevation acute coronary syndrome . Circulation, 2004,110:2342-2348
24. Michael G, Shlipak MD, Mark J, et al. Cystatin C and mortality in elderly persons with heart failure. Journal of the American College of Cardiology, 2005, 45(2): 268-271
25. Hans L, Jacobien C, Verhave J, et al. Cystatin C, a novel risk marker for mortality in the general population: data obtained from the PREVEND study. JACC, 2004, 3:190-194
26.刘航, 陈香美, 丁瑞,等.血清胱蛋白酶抑制剂C随增龄的变化.中国老年学杂志, 2005, 25 (5): 493-495
1. Simonsen O, Grubb A, Thysell H. The blood serum concentration of Cystatin C(gamma-trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest, 1985,45(2):97-101
2．裘晓蕙，钟光辉．Cystatin家族的研究进展．《癌症》，2001，20(2)：217-218
3. Abramhmson K, Olaffson Ⅰ, Palsdottir A, et al. Biochem J, 1990,268:287-299
4. Dickinson DP, Zhao Y, Thiese M, et al. Direct mapping of seven genes encoding human type 2 cystatins to a single site located 20p11. Genomics, 1994, 24(1): 172-175
5. Kyhse-Andersen J, Schmidt C, Nordin G, et al. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidmetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem, 1994,40(10):1921-1926
6. Finney H, Newman DJ, Gruber W, et al. Initial evaluation of cystatin Cmeasurement by particle-enhanced immunonephelometry on the Behring nephlometer systems(BNA,BNII). Clin Chem, 1997,43(6 pt 1):1061-1022
7. Dhamidharka VR, Kwon G, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function:a recta-analysis. Am J Kidney Dis, 2002,40(2):221-227
8. Bostom AG, Bausserman L, Jacques PF, et al. Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vasc Biol, 1999,19(9):2241-2244
9．任豫申，许迅辉．血清胱抑素C：在肌酐范围检测GFR的标志物．国外医学：泌尿系统分册，2002，22(5)：318-320
10. Shi G-P, Sukhova GK, Grubb A, et al. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest, 1999,104:1191-1197
11. Eriksson P, Deguchi H, Samnegard A, et al. Human evidence that the cystatin cgene is implicated in focal progression of coronary artery disease. Arterioscler Thromb Vase Biol, 2004,24:551-557
12. Lindholt JS, Erlandsen EJ, Henneberg EW. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg, 2001, 88:1472-1475
13．冯建芳，汪淑荣，李平，等．急性心机梗死病人血清巯基蛋白酶抑制肽C的变化．基础医学与临床，1995，15：45-4714. Davide Noto, Angelo Baldassare Cefalu, Carlo Maria Barbagallo, et al. Cystatin C levels are decreased in acute myocardial infarction. Effect of cystatin C G73 A gene polymorphism on plasma levels.International Journal of Cardiology, 2005, 101: 213-217
15. Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril :the HOPE randomized trisl. Ann Intern Med, 2001,134:629-636
16. Muntner P, He J, Hamm L, et al. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol, 2002,13:745-753
17. James SK, Lindahl B, Siegbahn A, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV substudy. Circulation, 2003,108:275-281
18. Januzzi JL Jr, Snapinn SM, DiBattiste PM, et al. Benefits and safety of tirofiban among acute coronary syndrome patients with mild to moderate renal insufficiency: results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS)trial. Circulation, 2002,105:2361-2366
19. Santopinto JJ, Fox KA, Goldberg RJ, et al. Creatinine clearance and adverse hospital outcomes in patients with acute Coronary syndromes:findings from the Global Registry of Acute Coronary Events (GRACE). Heart, 2003,89:1003-1008
20. Tomas J, Bertil L, Stefan J, et al. Cystatin C: a novel predictor of outcome in suspected or confirmed non-st-elevation acute coronary syndrome. Circulation, 2004,110:2342-2348
21. Wolfgang Koenig, Dorothee Twardella, Hermann Brenner, et al. Plasma concentration of cystatin c in patients with coronary heart disease and risk for secondary cardiovascular events : more than simply a marker of glomerular filtration rate. Clinical Chemistry, 2005,51(2):321-327
22. Michael G, Shlipak MD, Mark J, et al. Cystatin C and mortality in elderly persons with heart failure. Journal of the American College of Cardiology, 2005, 45(2): 268-271
23.张晓峰,吕洪太,董耀荣,等.Cystatin C在原发性高血压患者肾功能检测分
析中的应用. 放射免役学杂志, 2003, 16 (4): 253-256
24. Watanabe S, Okura T, Liu J, et al. Serum cystatin c level is a marker of end-organ damage in patients with essential hypertension. Hypertens Res Vol, 2003, 26(11); 895-899
25. Rickli H, Benou K, Ammann P, et al. Time course of serial cystatin c levels in comparison with serum creatinine after application of radiocontrast media. Clin Nephrol, 2004,61(2):98-102
26. Artunc FH, Fischer IU, Risler T, et al. Improved estimation of GFR by serum cystatin c in patients undergoing cardiac catheterization. Int J Cardiol, 2005, 102(2): 173-178
27. Hans L, Jacobien C, Verhave J, et al. Cystatin C, a novel risk marker for mortality in the general population: data obtained from the PREVEND study. JACC. Vascular Disease, Hypertention, and Prevention, 2004, 3 :1159-1194
2. Libby P. Molecular bases of the acute coronary syndromes. Circulation, 1995, 91: 2844-2850
3. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res, 2002,90:251-262
4. Thompson RW, Parks WC. Role of matrix metalloproteinases in abdominal aortic aneurysm. Ann N YAcad Sci, 1996, 800:157-174
5. Rao SK, Reddy KV, Cohen JR. Role of serine proteases in aneurysm development. Ann N Y Acad Sci, 1996, 800:131-137
6. Sukhova GK, Shi GP, Simon DI, et al. Expression of elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest, 1998, 102:576-583
7. Shimizu-Tokiwa A, Kobata M, Io H, et al. Serum Cystatin C is a more sensitive marker of glomerular function than serum creatinine. Nephron, 2002, 92:224-226
8. Chapman HA, Reilly J J, Yee R, et al. Identification of Cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. Am Rev Respir Dis, 1990, 141:698-705
9. Warfel AH, Zucker-Franklin D, Frangione B, et al. Constitutive secretion of Cystatin C by monocytes and macrophages and its downregulation after stimulation. J Exp Med,1987,166:1912-17
10. Shi GP, Sukhova GK, Grubb A, et al. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest, 1999, 104(9):1191-1197
11. Lindholt JS, Erlandsen EJ, Henneberg EW. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg, 2001, 88(11):1472-1475
12. Randers E, Erlandsen EJ. Serum Cystatin C as an endogenous marker of the renal function. Clin Chem Lab Med, 1999, 37(4):389
13．黄亚，石娟娟，忻鼎广，等。血清半胱氨酸蛋白酶抑制物C：肾功能的敏感指标。上海医学检验杂志，2001，16(5)
14．裘晓蕙，钟光辉，陈巍，等。应用血清西司他汀浓度测定肾小球滤过率的相关研究。中华肾脏病杂志，2001，17(1)：35-3615. Parks WC. Who are the proteolytic culprits in vascular disease? J Clin Invest, 1999, 104(9): 1167-1168
16. Davide Noto, Angelo Baldassare Cefalu, Carlo Maria Barbagallo, et al. Cystatin C levels are decreased in acute myocardial infarction. Effect of Cystatin C G73A gene polymorphism on plasma levels. International Journal of Cardiology, 2005, 101:213-217
17. Pfohl M, Schreiber I, Liebich HM, et al. Upregulation of cholesterol synthesis after acute myocardial infarction—is cholesterol a positive acute phase reactant? Atherosclerosis, 1999,142(2):389-393
18. Wattanasuwan N, Khan IA, Gowda RM, et al. Effect of acute myocardial infarction on cholesterol ratios. Chest, 2001, 120(4): 1196-1199
19. Eriksson P, Deguchi H, Samnegard A, et al. Human evidence that the Cystatin C gene is implicated in focal progression of coronary artery disease. Arterioscler Thromb Vasc Biol, 2004, 24:551-557
20. Bengtsson E, To F, Grubb A, et al. Absence of the protease inhibitor Cystatin C in inflammatory cells results in larger plaque area in plaque regression of apoE-deficient mice. Atherosclerosis, 2005,180(1 ):45-53
21. Johnston N, Jernberg T, Lindahl B, et al. Biochemical indicators of cardiac and renal function in a healthy elderly population. Clinical Biochemistry, 2004, 37 (3):210-216
22. Luc G, Bard JM, Lesueur C, et al. Plasma Cystatin C and development of coronary heart disease: The PRIME Study. Atherosclerosis, 2006,185(2):375-380
23. Tomas J, Bertil L, Stefan J, et al. Cystatin C: a novel predictor of outcome in suspected or confirmed non-st-elevation acute coronary syndrome . Circulation, 2004,110:2342-2348
24. Michael G, Shlipak MD, Mark J, et al. Cystatin C and mortality in elderly persons with heart failure. Journal of the American College of Cardiology, 2005, 45(2): 268-271
25. Hans L, Jacobien C, Verhave J, et al. Cystatin C, a novel risk marker for mortality in the general population: data obtained from the PREVEND study. JACC, 2004, 3:190-194
26.刘航, 陈香美, 丁瑞,等.血清胱蛋白酶抑制剂C随增龄的变化.中国老年学杂志, 2005, 25 (5): 493-495
1. Simonsen O, Grubb A, Thysell H. The blood serum concentration of Cystatin C(gamma-trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest, 1985,45(2):97-101
2．裘晓蕙，钟光辉．Cystatin家族的研究进展．《癌症》，2001，20(2)：217-218
3. Abramhmson K, Olaffson Ⅰ, Palsdottir A, et al. Biochem J, 1990,268:287-299
4. Dickinson DP, Zhao Y, Thiese M, et al. Direct mapping of seven genes encoding human type 2 cystatins to a single site located 20p11. Genomics, 1994, 24(1): 172-175
5. Kyhse-Andersen J, Schmidt C, Nordin G, et al. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidmetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem, 1994,40(10):1921-1926
6. Finney H, Newman DJ, Gruber W, et al. Initial evaluation of cystatin Cmeasurement by particle-enhanced immunonephelometry on the Behring nephlometer systems(BNA,BNII). Clin Chem, 1997,43(6 pt 1):1061-1022
7. Dhamidharka VR, Kwon G, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function:a recta-analysis. Am J Kidney Dis, 2002,40(2):221-227
8. Bostom AG, Bausserman L, Jacques PF, et al. Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vasc Biol, 1999,19(9):2241-2244
9．任豫申，许迅辉．血清胱抑素C：在肌酐范围检测GFR的标志物．国外医学：泌尿系统分册，2002，22(5)：318-320
10. Shi G-P, Sukhova GK, Grubb A, et al. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest, 1999,104:1191-1197
11. Eriksson P, Deguchi H, Samnegard A, et al. Human evidence that the cystatin cgene is implicated in focal progression of coronary artery disease. Arterioscler Thromb Vase Biol, 2004,24:551-557
12. Lindholt JS, Erlandsen EJ, Henneberg EW. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg, 2001, 88:1472-1475
13．冯建芳，汪淑荣，李平，等．急性心机梗死病人血清巯基蛋白酶抑制肽C的变化．基础医学与临床，1995，15：45-4714. Davide Noto, Angelo Baldassare Cefalu, Carlo Maria Barbagallo, et al. Cystatin C levels are decreased in acute myocardial infarction. Effect of cystatin C G73 A gene polymorphism on plasma levels.International Journal of Cardiology, 2005, 101: 213-217
15. Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril :the HOPE randomized trisl. Ann Intern Med, 2001,134:629-636
16. Muntner P, He J, Hamm L, et al. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol, 2002,13:745-753
17. James SK, Lindahl B, Siegbahn A, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV substudy. Circulation, 2003,108:275-281
18. Januzzi JL Jr, Snapinn SM, DiBattiste PM, et al. Benefits and safety of tirofiban among acute coronary syndrome patients with mild to moderate renal insufficiency: results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS)trial. Circulation, 2002,105:2361-2366
19. Santopinto JJ, Fox KA, Goldberg RJ, et al. Creatinine clearance and adverse hospital outcomes in patients with acute Coronary syndromes:findings from the Global Registry of Acute Coronary Events (GRACE). Heart, 2003,89:1003-1008
20. Tomas J, Bertil L, Stefan J, et al. Cystatin C: a novel predictor of outcome in suspected or confirmed non-st-elevation acute coronary syndrome. Circulation, 2004,110:2342-2348
21. Wolfgang Koenig, Dorothee Twardella, Hermann Brenner, et al. Plasma concentration of cystatin c in patients with coronary heart disease and risk for secondary cardiovascular events : more than simply a marker of glomerular filtration rate. Clinical Chemistry, 2005,51(2):321-327
22. Michael G, Shlipak MD, Mark J, et al. Cystatin C and mortality in elderly persons with heart failure. Journal of the American College of Cardiology, 2005, 45(2): 268-271
23.张晓峰,吕洪太,董耀荣,等.Cystatin C在原发性高血压患者肾功能检测分
析中的应用. 放射免役学杂志, 2003, 16 (4): 253-256
24. Watanabe S, Okura T, Liu J, et al. Serum cystatin c level is a marker of end-organ damage in patients with essential hypertension. Hypertens Res Vol, 2003, 26(11); 895-899
25. Rickli H, Benou K, Ammann P, et al. Time course of serial cystatin c levels in comparison with serum creatinine after application of radiocontrast media. Clin Nephrol, 2004,61(2):98-102
26. Artunc FH, Fischer IU, Risler T, et al. Improved estimation of GFR by serum cystatin c in patients undergoing cardiac catheterization. Int J Cardiol, 2005, 102(2): 173-178
27. Hans L, Jacobien C, Verhave J, et al. Cystatin C, a novel risk marker for mortality in the general population: data obtained from the PREVEND study. JACC. Vascular Disease, Hypertention, and Prevention, 2004, 3 :1159-1194