Cardiovascular Drugs and Therapy

, Volume 24, Issue 4, pp 311–317

Atherosclerotic Plaque Regression: Fact or Fiction?

  • Nesan Shanmugam
  • Ana Román-Rego
  • Peter Ong
  • Juan Carlos Kaski


Coronary artery disease is the major cause of death in the western world. The formation and rapid progression of atheromatous plaques can lead to serious cardiovascular events in patients with atherosclerosis. The better understanding, in recent years, of the mechanisms leading to atheromatous plaque growth and disruption and the availability of powerful HMG CoA-reductase inhibitors (statins) has permitted the consideration of plaque regression as a realistic therapeutic goal. This article reviews the existing evidence underpinning current therapeutic strategies aimed at achieving atherosclerotic plaque regression. In this review we also discuss imaging modalities for the assessment of plaque regression, predictors of regression and whether plaque regression is associated with a survival benefit.

Key words

Atherosclerosis Atheromatous plaque regression Statins IVUS Cardiac magnetic resonance 


  1. 1.
    Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet. 1997;349:1436–42.CrossRefPubMedGoogle Scholar
  2. 2.
    Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–95.CrossRefPubMedGoogle Scholar
  3. 3.
    Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–65.CrossRefPubMedGoogle Scholar
  4. 4.
    Halvorsen B, Otterdal K, Dahl TB, Skjelland M, Gullestad L, Øie E, et al. Atherosclerotic plaque stability—what determines the fate of a plaque? Prog Cardiovasc Dis. 2008;51:183–94.CrossRefPubMedGoogle Scholar
  5. 5.
    Stary HC. Atlas of atherosclerosis: progression and regression. The Encyclopedia of Visual Medicine Series. New York: The Parthenon publishing group; 1999.Google Scholar
  6. 6.
    Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.CrossRefPubMedGoogle Scholar
  7. 7.
    Klein LW. Atherosclerosis regression, vascular remodeling, and plaque stabilization. J Am Coll Cardiol. 2007;49:271–3.CrossRefPubMedGoogle Scholar
  8. 8.
    Blankenhorn DH, Azen SP, Kramsch DM, Mack WJ, Cashin-Hemphill L, Hodis HN, et al. Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med. 1993;119:969–76.PubMedGoogle Scholar
  9. 9.
    Waters D, Higginson L, Gladstone P, Kimball B, Le May M, Boccuzzi SJ. Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial. Circulation. 1994;89:959–68.PubMedGoogle Scholar
  10. 10.
    Jukema JW, Bruschke AV, van Boven AJ, Reiber JH, Bal ET, Zwinderman AH, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation. 1995;91:2528–40.PubMedGoogle Scholar
  11. 11.
    Pitt B, Mancini GB, Ellis SG, Rosman HS, Park JS, McGovern ME. McGovern ME.Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation. J Am Coll Cardiol. 1995;26:1133–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289–98.CrossRefPubMedGoogle Scholar
  13. 13.
    MAAS Study Group. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet. 1994;344:633–8.CrossRefGoogle Scholar
  14. 14.
    Williams KJ, Feig JE, Fisher EA. Rapid regression of atherosclerosis: insights from the clinical and experimental literature. Nat Clin Pract Cardiovasc Med. 2008;5:91–102.CrossRefPubMedGoogle Scholar
  15. 15.
    Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, U-King-Im JM, et al. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009;53:2039–50.CrossRefPubMedGoogle Scholar
  16. 16.
    Callister TQ, Raggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med. 1998;339:1972–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol. 1997;146:483–94.PubMedGoogle Scholar
  18. 18.
    Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, et al. The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med. 1998;128:262–9.PubMedGoogle Scholar
  19. 19.
    Jang IK, Bouma BE, Kang DH, Park SJ, Park SW, Seung KB, et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol. 2002;39:604–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Aoki J, Rodríguez-Granillo GA, Serruys PW. Emergent strategies in interventional cardiology. Rev Esp Cardiol. 2005;58:962–73.CrossRefPubMedGoogle Scholar
  21. 21.
    Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation. 2002;106:2200–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Schaar JA, de Korte CL, Mastik F, Baldewsing R, Regar E, de Feyter P, et al. Intravascular palpography for high-risk vulnerable plaque assessment. Herz. 2003;28:488–95.CrossRefPubMedGoogle Scholar
  23. 23.
    Corti R. Noninvasive imaging of atherosclerotic vessels by MRI for clinical assessment of the effectiveness of therapy. Pharmacol Ther. 2006;110:57–70.CrossRefPubMedGoogle Scholar
  24. 24.
    Ruehm SG, Corot C, Vogt P, Cristina H, Debatin JF. Ultrasmall superparamagnetic iron oxide-enhanced MR imaging of atherosclerotic plaque in hyperlipidemic rabbits. Acad Radiol. 2002;9 Suppl 1:S143–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Ortego M, Bustos C, Hernández-Presa MA, Tuñón J, Díaz C, Hernández G, et al. Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis. 1999;147:253–61.CrossRefPubMedGoogle Scholar
  26. 26.
    Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–80.CrossRefPubMedGoogle Scholar
  27. 27.
    Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, et al. Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med. 2005;352:29–38.CrossRefPubMedGoogle Scholar
  28. 28.
    Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297:499–508.CrossRefPubMedGoogle Scholar
  29. 29.
    Underhill HR, Yuan C, Zhao XQ, Kraiss LW, Parker DL, Saam T, et al. Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial. Am Heart J. 2008;155:584.e1–8.Google Scholar
  30. 30.
    Yonemura A, Momiyama Y, Fayad ZA, Ayaori M, Ohmori R, Higashi K, et al. Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging. J Am Coll Cardiol. 2005;45:733–42.CrossRefPubMedGoogle Scholar
  31. 31.
    Lima JA, Desai MY, Steen H, Warren WP, Gautam S, Lai S. Statin-induced cholesterol lowering and plaque regression after 6 months of magnetic resonance imaging-monitored therapy. Circulation. 2004;110:2336–41.CrossRefPubMedGoogle Scholar
  32. 32.
    Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation. 2001;103:926–33.PubMedGoogle Scholar
  33. 33.
    Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, et al. Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years’ follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002;106:2884–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Gordon DF, Rifkind BM. High-density lipoprotein: the clinical implications of recent studies. N Engl J Med. 1989;321:1311–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583–92.CrossRefPubMedGoogle Scholar
  36. 36.
    Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology 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.CrossRefPubMedGoogle Scholar
  37. 37.
    Airan-Javia SL, Wolf RL, Wolfe ML, Tadesse M, Mohler E, Reilly MP. Atheroprotective lipoprotein effects of a niacin-simvastatin combination compared to low- and high-dose simvastatin monotherapy. Am Heart J. 2009;157:687.e1–8.Google Scholar
  38. 38.
    Lee JM, Robson MD, Yu LM, Shirodaria CC, Cunnington C, Kylintireas I, et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol. 2009;54:1787–94.CrossRefPubMedGoogle Scholar
  39. 39.
    Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290:2292–300.CrossRefPubMedGoogle Scholar
  40. 40.
    Waksman R, Kent K, Pichard A, Suddath W, Satler L, Martin D, et al. Abstract 1697: A First-In Man, Randomized, Placebo-Controlled Study to Evaluate the Safety and Feasibility of Autologous Delipidated High Density Lipoprotein Plasma Infusions in Patients With Acute Coronary Syndrome. Circulation. 2008;118:S_371.Google Scholar
  41. 41.
    Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. Renin-angiotensin system and cardiovascular risk. Lancet. 2007;369:1208–19.CrossRefPubMedGoogle Scholar
  42. 42.
    Miyazaki M, Sakonjo H, Takai S. Anti-atherosclerotic effects of an angiotensin converting enzyme inhibitor and an angiotensin II antagonist in Cynomolgus monkeys fed a high-cholesterol diet. Br J Pharmacol. 1999;128:523–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Tani S, Nagao K, Anazawa T, Kawamata H, Furuya S, Takahashi H, et al. Relation of change in apolipoprotein B/apolipoprotein A-I ratio to coronary plaque regression after Pravastatin treatment in patients with coronary artery disease. Am J Cardiol. 2010;105:144–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, et al. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.CrossRefPubMedGoogle Scholar
  45. 45.
    Tani S, Nagao K, Anazawa T, Kawamata H, Furuya S, Takahashi H, et al. Association of leukocyte subtype counts with coronary atherosclerotic regression following pravastatin treatment. Am J Cardiol. 2009;104:464–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Nesan Shanmugam
    • 1
  • Ana Román-Rego
    • 1
  • Peter Ong
    • 1
  • Juan Carlos Kaski
    • 1
  1. 1.Division of Cardiac and Vascular SciencesSt George’s University of LondonLondonUK

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