Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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The Effects of Statin and Niacin on Plaque Stability, Plaque Regression, Inflammation and Oxidative Stress in Patients With Mild to Moderate Coronary Artery Stenosis

  • Lee, Kyoung-Hoon (Department of Cardiology, Gil Hospital, Gachon University of Medicine and Science) ;
  • Ahn, Tae-Hoon (Department of Cardiology, Gil Hospital, Gachon University of Medicine and Science) ;
  • Kang, Woong-Chol (Department of Cardiology, Gil Hospital, Gachon University of Medicine and Science) ;
  • Han, Seung-Hwan (Department of Cardiology, Gil Hospital, Gachon University of Medicine and Science) ;
  • Choi, In-Suck (Department of Cardiology, Gil Hospital, Gachon University of Medicine and Science) ;
  • Shin, Eak-Kyun (Department of Cardiology, Gil Hospital, Gachon University of Medicine and Science)
  • Published : 2011.11.30
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Abstract

Background and Objectives: The aim of this study was to compare the effects of a combination of niacin and simvastatin to simvastatin alone, on plaque regression and inflammatory makers. Subjects and Methods: The study had a prospective, randomized design. Subjects were patients with intermediate coronary artery stenosis. A total of 28 patients received a combination of niacin 1,000 mg plus simvastatin 40 mg (N+S group, n=14); the other group received simvastatin 40 mg alone (S group, n=14). All patients had a baseline and a 9-month follow-up coronary angiogram and an intravascular ultrasound procedure. Parameters such as normalized total atheroma volume (nTAV) and percent atheroma volume (PAV) were analyz-ed before and after treatment as were inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), Matrix me-talloproteinase-9 (MMP-9) and soluble CD40 ligand (sCD40L). Results: There was no difference in baseline characteristics between the two groups. The nTAV and PAV in the N+S group before and after treatment were not different than those in the S group. But the degree of changes (delta) in nTAV in the N+S group was greater than that in the S group (-21.6${\pm}$10.68 vs. 5.25${\pm}$42.19, respectively, p=0.024). Also, the change in PAV in the NS group was higher than that in the S group (-1.2${\pm}$2.5 vs. -0.6${\pm}$5, respectively, p=0.047. Changes in hs-CRP, MMP-9, and sCD40L in the NS group were significantly greater than those of the S group (-0.71${\pm}$1.25, 73.5${\pm}$64.9, -1,970${\pm}$1,925 vs. -0.32${\pm}$0.96, 62.5${\pm}$30.6, -1,673${\pm}$2,628, respectively). Conclusion: The combination of niacin plus simvastatin decreases coronary plaque volume and attenuates the inflammatory response in patients with intermediate coronary artery stenosis.

Keywords

References

  1. The Scandinavian Simvastatin Survival Study (4S). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
  2. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333: 1301-7. https://doi.org/10.1056/NEJM199511163332001
  3. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996;335:1001-9. https://doi.org/10.1056/NEJM199610033351401
  4. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57. https://doi.org/10.1056/NEJM199811053391902
  5. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four Prospective American Studies. Circulation 1989;79:8-15. https://doi.org/10.1161/01.CIR.79.1.8
  6. Kannel WB. Range of serum cholesterol values in the population developing coronary artery disease. Am J Cardiol 1995;76:C69-77. https://doi.org/10.1016/S0002-9149(99)80474-3
  7. The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421.
  8. Meyers CD, Kamanna VS, Kashyap ML. Niacin therapy in atherosclerosis. Curr Opin Lipidol 2004;15:659-65. https://doi.org/10.1097/00041433-200412000-00006
  9. Carlson LA. Nicotinic acid: the broad-spectrum lipid drug: a 50th anniversary review. J Intern Med 2005;258:94-114. https://doi.org/10.1111/j.1365-2796.2005.01528.x
  10. Sakai T, Kamanna VS, Kashyap ML. Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol. Arterioscler Thromb Vasc Biol 2001;21:1783-9. https://doi.org/10.1161/hq1001.096624
  11. Taylor AJ, Zhu D, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2. Vasc Health Risk Manag 2007;3:159-64.
  12. Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 2006;22:2243-50. https://doi.org/10.1185/030079906X148508
  13. Mintz GS, Nissen SE, Anderson WD, et al. A report of the American College of Cardiology Task Force on clinical expert consensus documents. American College of Cardiology Clinical Expert Consensus Do-cument on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). J Am Coll Cardiol 2001;37: 1478-92. https://doi.org/10.1016/S0735-1097(01)01175-5
  14. Park SY, Kwak JJ, Park SH. Dose dependent changes of lipid profiles, IL-6 and CRP in unstable angina patients after simvastatin therapy. Korean Circ J 2003;33:663-70.
  15. Son JW, Koh KK. Effects of statins on endothelium: vasomotor function, inflammation, and hemostasis. Korean Circ J 1999;29:1016-31.
  16. Hong YJ, Jeong MH, Ahn YK, et al. Effect of conventional dose of si-mvastatin on plaque regression and vascular remodeling in the peristent reference segments of normocholesterolemic patients: a serial in-travascular ultrasound assessment. Korean Circ J 2007;37:483-8. https://doi.org/10.4070/kcj.2007.37.10.483
  17. Hong YJ, Jeong MH, Lim JH, et al. The prognostic significance of statin therapy according to the level of C-reactive protein in acute myo-cardial infarction patients who underwent percutaneous coronary intervention. Korean Circ J 2003;33:891-900.
  18. Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity st-atin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006;295:1556-65. https://doi.org/10.1001/jama.295.13.jpc60002
  19. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-92. https://doi.org/10.1056/NEJMoa011090
  20. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial bio-logy for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004;110:3512-7. https://doi.org/10.1161/01.CIR.0000148955.19792.8D
  21. Cipollone F, Mezzetti A, Porreca E, et al. Association between enhanc-ed soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy. Circulation 2002;106:399-402. https://doi.org/10.1161/01.CIR.0000025419.95769.F0
  22. Tomai F, Crea F, Gaspardone A, et al. Unstable angina and elevated c-reactive protein levels predict enhanced vasoreactivity of the culprit lesion. Circulation 2001;104:1471-6. https://doi.org/10.1161/hc3801.096354
  23. Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 2000;102:1000-6. https://doi.org/10.1161/01.CIR.102.9.1000
  24. Son JW, Koh KK, Ahn JY, et al. Effects of statin on plaque stability and thrombogenicity in hypercholesterolemic patients with coronary artery disease. Int J Cardiol 2003;88:77-82. https://doi.org/10.1016/S0167-5273(02)00368-6
  25. Fernandez-Patron C, Martinez-Cuesta MA, Salas E, et al. Differential regulation of platelet aggregation by matrix metalloproteinases-9 and -2. Thromb Haemost 1999;82:1730-5.
  26. Lelongt B, Bengatta S, Delauche M, Lund LR, Werb Z, Ronco PM. Matrix metalloproteinase 9 protects mice from anti-glomerular basement membrane nephritis through its fibrinolytic activity. J Exp Med 2001;193:793-802. https://doi.org/10.1084/jem.193.7.793
  27. Fontaine V, Jacob MP, Houard X, et al. Involvement of the mural th-rombus as a site of protease release and activation in human aortic aneurysms. Am J Pathol 2002;161:1701-10. https://doi.org/10.1016/S0002-9440(10)64447-1
  28. Tang J, Liu J, Zhou C, et al. Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. J Cereb Blood Flow Metab 2004;24:1133-45. https://doi.org/10.1097/01.WCB.0000135593.05952.DE
  29. Johnson JL, George SJ, Newby AC, Jackson CL. Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque st-ability in mouse brachiocephalic arteries. Proc Natl Acad Sci U S A 2005;102:15575-80. https://doi.org/10.1073/pnas.0506201102

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