American Journal of Cardiovascular Drugs

, Volume 9, Issue 2, pp 109–115 | Cite as

Effects on Coronary Atherosclerosis by Targeting Low-Density Lipoprotein Cholesterol with Statins

Review Article

Abstract

A correlation exists between circulating levels of low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular disease (CVD). Evidence from clinical trials indicates that reducing LDL-C levels can result in beneficial clinical outcomes in patients at risk of CVD and in high-risk patients with clinical symptoms of CVD. Lipid-lowering agents, of which HMG-CoA reductase inhibitors (statins) are the most effective, protect against the vascular changes seen in the development of atherosclerotic plaque formation. Clinical trials assessing the effects of statins on coronary atherosclerosis using quantitative coronary angiography or intravascular ultrasound showed that statins can reduce progression or even cause regression of atherosclerotic plaque. This improvement of vascular structure after statin treatment is correlated with reductions in LDL-C levels. This appears to be the principal mechanism by which statin therapy reduces cardiovascular risk, with emerging evidence for statin-mediated changes in high-density lipoprotein and C-reactive protein levels contributing to modification of the atherosclerotic plaque.

Notes

Acknowledgments

Wolters Kluwer Health Medical Communications provided writing assistance on behalf of Astra Zeneca. Professor Ferrières received an honorarium from Astra Zeneca for the preparation of this manuscript; received honoraria from Astra Zeneca, Bristol Myers Squibb, Sanofi Aventis, and Pfizer, and received grants from Bristol Myers Squibb, Pfizer, and Sanofi Aventis. Professor Ferrières has no other potential conflicts of interest that may be relevant to the contents of this article.

References

  1. 1.
    European mortality database [online database]. Copenhagen: WHO Regional Office for Europe, 2007 [online]. Available from URL: http://www.euro.who.int/InformationSources/Data/20011017_1 [Accessed 2009 Feb 26].
  2. 2.
    National Institute for Statistics and Economic Studies (INSEE). France in facts and figures: main causes of death. 2008 [online]. Available from URL: http://www.insee.fr/fr/themes/tableau.asp?reg_id=0&ref_id=NATFPS06205 [Accessed 2009 Feb 26].
  3. 3.
    National Institute for Health and Clinical Excellence. Technology Appraisal 94: statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease [online]. Available from URL: http://www.nice.org.uk/Guidance/TA94 [Accessed 2009 Feb 26].
  4. 4.
    Kruth HS. Lipoprotein cholesterol and atherosclerosis. Curr Mol Med 2001 Dec; 1(6): 633–53PubMedCrossRefGoogle Scholar
  5. 5.
    Croce K, Libby P. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 2007 Jan; 14(1): 55–61PubMedCrossRefGoogle Scholar
  6. 6.
    NCEP. 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 Dec 17; 106(25): 3143–421Google Scholar
  7. 7.
    Gordon D, Probstfield JL, Garrison RJ, et al. High density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989; 79: 8–15PubMedCrossRefGoogle Scholar
  8. 8.
    Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol lower risk of ischemic heart disease? BMJ 1994; 308: 367–72PubMedCrossRefGoogle Scholar
  9. 9.
    Saini HK, Xu YJ, Arneja AS, et al. Pharmacological basis of different targets for the treatment of atherosclerosis. J Cell Mol Med 2005 Oct–Dec; 9(4): 818–39PubMedCrossRefGoogle Scholar
  10. 10.
    Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–43PubMedCrossRefGoogle Scholar
  11. 11.
    Tuzcu EM, Nicholls SJ. Statins: targeting inflammation by lowering lowdensity lipoprotein. J Am Coll Cardiol 2007; 49(20): 2010–2PubMedCrossRefGoogle Scholar
  12. 12.
    Sankatsing RR, de Groot E, Jukema JW, et al. Surrogate markers for atherosclerotic disease. Curr Opin Lipidol 2005 Aug; 16(4): 434–41PubMedCrossRefGoogle Scholar
  13. 13.
    Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness consensus (2004–2006). An update on behalf of the advisory board of the 3rd and 4th Watching the Risk Symposium 13th and 15th European stroke conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis 2007; 23(1): 75–80PubMedCrossRefGoogle Scholar
  14. 14.
    Bisoendial RJ, Hovingh GK, de Groot E, et al. Measurement of subclinical atherosclerosis: beyond risk factor assessment. Curr Opin Lipidol 2002 Dec; 13(6): 595–603PubMedCrossRefGoogle Scholar
  15. 15.
    Staub D, Meyerhans A, Bundi B, et al. Prediction of cardiovascular morbidity and mortality: comparison of the internal carotid artery resistive index with the common carotid artery intima-media thickness. Stroke 2006 Mar; 37(3): 800–5PubMedCrossRefGoogle Scholar
  16. 16.
    Berry C, L’Allier PL, Gregoire J, et al. Comparison of intravascular ultrasound and quantitative coronary angiography for the assessment of coronary artery disease progression. Circulation 2008; 115: 1851–7CrossRefGoogle Scholar
  17. 17.
    Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006 Apr 5; 295(13): 1556–65PubMedCrossRefGoogle Scholar
  18. 18.
    Brown BG, Zhao X-Q. Is intravascular ultrasound the gold standard surrogate for clinically relevant atherosclerosis progression? J Am Coll Cardiol 2007; 49(9): 933–8PubMedCrossRefGoogle Scholar
  19. 19.
    Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004 Mar 3; 291(9): 1071–80PubMedCrossRefGoogle Scholar
  20. 20.
    Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004 Jul 13; 110(2): 227–39PubMedCrossRefGoogle Scholar
  21. 21.
    Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J 2009 Jan; 157(1): 111–7.e2PubMedCrossRefGoogle Scholar
  22. 22.
    MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 Jul 6; 360(9326): 7–22CrossRefGoogle Scholar
  23. 23.
    Patel T, Usmani A, Bavry A, et al. Relationship between intensive statin therapy and cardiovascular outcomes in patients with stable coronary artery disease: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 2007; 49(9 Suppl. A): 245Google Scholar
  24. 24.
    Brown BG, Stukovsky KH, Zhao X-Q. Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and their combinations: a meta-analysis of 23 randomized trials. Curr Opin Lipidol 2006; 17: 631–6PubMedCrossRefGoogle Scholar
  25. 25.
    Lennernas H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet 1997 May; 32(5): 403–25PubMedCrossRefGoogle Scholar
  26. 26.
    Bulbulia R, Bowman L, Wallendszus K. MRC/BHF Heart Protection Study (HPS): mortality, cancer incidence and major vascular events during 4 years post-trial follow-up of HPS. J Am Coll Cardiol 2007; 49(9 Suppl. A): 393Google Scholar
  27. 27.
    Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003 Jun 28; 326(7404): 1423PubMedCrossRefGoogle Scholar
  28. 28.
    Balamuthusamy S, Molnar J, Adigopula S. Statins decrease the risk of acute myocardial infarction and coronary heart disease mortality in patients with renal failure. J Am Coll Cardiol 2007; 49(9 Suppl. A): 188–9Google Scholar
  29. 29.
    Saha S, Saremi A, Velasquez-Cecena J-L. Statins reduce the risk of death and the occurrence of adverse cardiovascular events in patients with dyslipidemia and renal dysfunction: a meta-analysis of randomized placebo-controlled trials. Am J Cardiol 2007; 49(9 Suppl. A): 344Google Scholar
  30. 30.
    Brown BG, Zhao X-Q, Sacco DE, et al. Arteriographic view of treatment to achieve regression of coronary atherosclerosis and to prevent plaque disruption and clinical cardiovascular events. Br Heart J 1993; 69 Suppl.: S48–53PubMedCrossRefGoogle Scholar
  31. 31.
    Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic changes with lovastatin therapy: the Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 1993; 119(10): 966–76Google Scholar
  32. 32.
    Thompson GR, Hollyer J, Waters DD. Percentage change rather than plasma level of LDL-cholesterol determines therapeutic response in coronary heart disease. Curr Opin Lipidol 1995 Dec; 6(6): 386–8PubMedCrossRefGoogle Scholar
  33. 33.
    Ballantyne CM, Herd JA, Dunn JK, et al. Effects of lipid lowering therapy on progression of coronary and carotid artery disease. Curr Opin Lipidol 1997 Dec; 8(6): 354–61PubMedCrossRefGoogle Scholar
  34. 34.
    Ballantyne CM, Raichlen JS, Nicholls SJ, et al. Effect of rosuvastatin therapy on coronary artery stenoses assessed by quantitative coronary angiography: a study to evaluate the effect of rosuvastatin on intravascular ultrasoundderived coronary atheroma burden. Circulation 2008; 117: 2458–66PubMedCrossRefGoogle Scholar
  35. 35.
    Crouse J, Grobbee D, O’Leary D, on behalf of the METEOR Study Group. Rosuvastatin arrests progression of carotid intima media thickness in low risk individuals: main results of the METEOR study. Am J Cardiol 2007; 49(9 Suppl. A): 392–3Google Scholar
  36. 36.
    Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007; 297(5): 499–508PubMedCrossRefGoogle Scholar
  37. 37.
    O’Keefe Jr JH, Cordain L, Harris WH, et al. Optimal low-density lipoprotein is 50 to 70mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 2004 Jun 2; 43(11): 2142–6PubMedCrossRefGoogle Scholar
  38. 38.
    Nicholls SJ, Sipahi I, Crowe T. Baseline lipid status does not influence the promotion of coronary atheroma regression in response to use of high dose statin therapy: insights from ASTEROID. Am J Cardiol 2007; 49(9 Suppl. A): 365Google Scholar
  39. 39.
    Sipahi I, Tuzcu M, Nicholls SJ. Regression of coronary atherosclerosis during treatment with statins: does age make a difference? Am J Cardiol 2007; 49(9 Suppl. A): 336Google Scholar
  40. 40.
    Takashima H, Asai K, Wakita Y. Impact of HMG-CoA reductase inhibitors (statins) on new cardiovascular events following coronary intervention and on the progression-regression of coronary atherosclerotic plaque: a three-dimensional intravascular ultrasound study. Am J Cardiol 2007; 49(9 Suppl. A): 325Google Scholar
  41. 41.
    Hausenloy DJ, Yellon DM. Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. Heart 2008; 94: 706–14PubMedCrossRefGoogle Scholar
  42. 42.
    Nicholls SJ, Tuzcu EM, Sipahi I. Statin-mediated increases in HDL cholesterol promote regression of coronary atherosclerosis: insights from intravascular ultrasound. Am J Cardiol 2007; 49(9 Suppl. A): 365Google Scholar
  43. 43.
    Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein and coronary artery disease. N Engl J Med 2005; 352(1): 29–38PubMedCrossRefGoogle Scholar
  44. 44.
    Kinlay S. Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein. J Am Coll Cardiol 2007; 49(20): 2003–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Department of CardiologyToulouse University School of Medicine, Rangueil HospitalToulouseFrance

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