Re-Elevation of High-Sensitivity C-Reactive Protein but not the von Willebrand Factor After Withdrawing Atorvastatin Therapy in Patients With Unstable Angina Undergoing Coronary Artery Stenting A Kinetic Study
Statins are known to reduce high-sensitivity C-reactive protein (hs-CRP) concentrations and improve endothelial function. However, whether statin withdrawal causes re-elevated concentrations of hs-CRP and von Willebrand Factor (vWF) (a marker of endothelial damage) remains unknown. We hypothesized t...
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| Published in | International Heart Journal Vol. 47; no. 4; pp. 501 - 509 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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International Heart Journal Association
2006
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| ISSN | 1349-2365 1349-3299 |
| DOI | 10.1536/ihj.47.501 |
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| Abstract | Statins are known to reduce high-sensitivity C-reactive protein (hs-CRP) concentrations and improve endothelial function. However, whether statin withdrawal causes re-elevated concentrations of hs-CRP and von Willebrand Factor (vWF) (a marker of endothelial damage) remains unknown. We hypothesized that the concentrations of hs-CRP and vWF are substantially increased in patients with unstable angina pectoris (UAP) and noticeably decreased following coronary stenting along with atorvastatin therapy. However, re-elevations of these biomarker concentrations occurred once again after withdrawing atorvastatin therapy. We serially examined the plasma concentrations of hs-CRP and vWF in 51 patients with UAP before (day 0) and after (days 21, 90, 180, 270) performing coronary artery stenting. The concentrations of these 2 biomarkers were also measured in 30 healthy control subjects. Patients were treated with atorvastatin (40 mg/day orally) for 180 days, after which the therapy was withdrawn. The hs-CRP and vWF concentrations were significantly higher in the patients than in the healthy control subjects before the procedure (both P values < 0.001). The hs-CRP concentration decreased significantly on day 21 (P < 0.001), and further to a substantially lower level on day 180 (P < 0.0001). However, the hs-CRP level significantly increased again on day 270, as compared with that on day 180 (P < 0.001). The vWF plasma concentration decreased gradually to a significantly lower level on day 180. The concentration of this biomarker did not differ between days 180 and 270. In conclusion, although hs-CRP concentrations decreased markedly following combined stenting and atorvastatin therapy, re-elevation after atorvastatin therapy was withdrawn in UAP patients undergoing coronary stenting was not observed. Conversely, restoration of endothelial function was slow and persistent in these patients. |
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| AbstractList | Statins are known to reduce high-sensitivity C-reactive protein (hs-CRP) concentrations and improve endothelial function. However, whether statin withdrawal causes re-elevated concentrations of hs-CRP and von Willebrand Factor (vWF) (a marker of endothelial damage) remains unknown. We hypothesized that the concentrations of hs-CRP and vWF are substantially increased in patients with unstable angina pectoris (UAP) and noticeably decreased following coronary stenting along with atorvastatin therapy. However, re-elevations of these biomarker concentrations occurred once again after withdrawing atorvastatin therapy. We serially examined the plasma concentrations of hs-CRP and vWF in 51 patients with UAP before (day 0) and after (days 21, 90, 180, 270) performing coronary artery stenting. The concentrations of these 2 biomarkers were also measured in 30 healthy control subjects. Patients were treated with atorvastatin (40 mg/day orally) for 180 days, after which the therapy was withdrawn. The hs-CRP and vWF concentrations were significantly higher in the patients than in the healthy control subjects before the procedure (both P values < 0.001). The hs-CRP concentration decreased significantly on day 21 (P < 0.001), and further to a substantially lower level on day 180 (P < 0.0001). However, the hs-CRP level significantly increased again on day 270, as compared with that on day 180 (P < 0.001). The vWF plasma concentration decreased gradually to a significantly lower level on day 180. The concentration of this biomarker did not differ between days 180 and 270. In conclusion, although hs-CRP concentrations decreased markedly following combined stenting and atorvastatin therapy, re-elevation after atorvastatin therapy was withdrawn in UAP patients undergoing coronary stenting was not observed. Conversely, restoration of endothelial function was slow and persistent in these patients. |
| Author | Chua, Sarah Wu, Chiung-Jen Yip, Hon-Kan Youssef, Ali A. Hang, Chi-Ling Yeh, Kuo-Ho Hung, Wei-Chin Chen, Yen-Hsun |
| Author_xml | – sequence: 1 fullname: Hang, Chi-Ling organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine – sequence: 1 fullname: Yip, Hon-Kan organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine – sequence: 1 fullname: Youssef, Ali A. organization: Cardiology Department, Suez Canal University Hospital – sequence: 1 fullname: Hung, Wei-Chin organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine – sequence: 1 fullname: Wu, Chiung-Jen organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine – sequence: 1 fullname: Chua, Sarah organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine – sequence: 1 fullname: Chen, Yen-Hsun organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine – sequence: 1 fullname: Yeh, Kuo-Ho organization: Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine |
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| Cites_doi | 10.1161/01.CIR.0000012625.02748.62 10.1161/01.CIR.0000089191.72957.ED 10.1161/01.ATV.0000081637.36475.BC 10.1253/circj.69.1202 10.1056/NEJM199901143400207 10.1161/01.CIR.0000077912.12202.FC 10.1253/circj.70.838 10.1161/01.CIR.0000089190.95415.9F 10.1016/S0021-9150(02)00316-7 10.1161/01.CIR.0000015507.29953.38 10.1253/circj.69.890 10.1161/01.CIR.80.2.410 10.1378/chest.127.3.803 10.1161/01.CIR.0000023397.12047.03 10.1161/01.CIR.99.2.237 10.1016/S0002-9149(02)03156-9 10.1161/01.CIR.89.1.36 10.1111/j.1749-6632.1997.tb51996.x 10.1161/01.CIR.102.18.2165 10.1056/NEJMoa021993 10.1161/01.CIR.0000033220.97592.9A 10.1016/S0002-9149(02)03268-X 10.1378/chest.126.5.1417 |
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| References_xml | – reference: 5. Mueller C, Buettner HJ, Hodgson JM, et al. Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients. Circulation 2002; 105: 1412-5. – reference: 7. Yip HK, Hung WC, Yang CH, et al. Serum concentrations of high-sensitivity C-reactive protein predict progressively obstructive lesions rather than late restenosis in patients with unstable angina undergoing coronary artery stenting. Circ J 2005; 69: 1202-7. – reference: 9. Ridker PM, Rifai N, Rose L, Buring JE, Cook N. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347: 1557-65. – reference: 19. Ishikawa T, Hatakeyama K, Imamura T, et al. Involvement of C-reactive protein obtained by directional coronary atherectomy in plaque instability and developing restenosis in patients with stable or unstable angina pectoris. Am J Cardiol 2003; 91: 287-92. – reference: 11. Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation 2003; 108: 2054-9. (Review) – reference: 22. Kinlay S, Selwyn AP. Effects of statins on inflammation in patients with acute and chronic coronary syndromes. Am J Cardiol 2003; 91(suppl): 9B-13. (Review) – reference: 12. Yip HK, Wu CJ, Yang CH, et al. 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: 890-5. – reference: 2. Libby P, Geng YJ, Sukhova GK, Simon DI, Lee RT. Molecular determinants of atherosclerotic plaque vulnerability. Ann N Y Acad Sci 1997; 811: 134-42; discussion 142-5. 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Chest 2005; 127: 803-8. – reference: 20. Yip HK, Sun CK, Chang LT, Wu CJ. Strong correlation between serum levels of inflammatory mediators and their distribution in infarct coronary artery. Circ J 2006; 70: 838-45. – reference: 18. Burke AP, Tracy RP, Kologie F, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation 2002; 105: 2019-23. – reference: 16. Kobayashi S, Inoue N, Ohashi Y, et al. Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of C-reactive protein. Arterioscler Thromb Vasc Biol 2003; 23: 1398-404. – reference: 1. 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. – reference: 8. Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99: 237-42. – reference: 4. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102; 2165-8. – reference: 21. Yeung AC, Tsao P. Statin therapy: beyond cholesterol lowering and anti-inflammatory effects. Circulation 2002; 105: 2937-8. – reference: 15. Braunwald E. Unstable angina. A classification. Circulation 1989; 80: 410-4. – reference: 14. Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003; 107: 3141-5. – reference: 23. Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 1321 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors. 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| Subtitle | A Kinetic Study |
| Title | Re-Elevation of High-Sensitivity C-Reactive Protein but not the von Willebrand Factor After Withdrawing Atorvastatin Therapy in Patients With Unstable Angina Undergoing Coronary Artery Stenting |
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