Journal of Vascular Surgery
Volume 51, Issue 1 , Pages 114-121 , January 2010

Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization

Presented at the Society for Vascular Surgery Annual Meeting, Denver, Colo, Jun 11-14, 2009.

  • Nikolaos P.E. Kadoglou, MD

      Affiliations

    • First Department of Internal Medicine, “Hippokratio” General Hospital of Thessaloniki, Thessaloniki, Greece
    • Department of Vascular Surgery, Medical School, University of Athens, Athens, Greece
    • Corresponding Author InformationReprint requests: Nikolaos P.E. Kadoglou, 124 Vosporou str, GR-54454 Thessaloniki Greece
    • ,
  • Nikolaos Sailer, MD

      Affiliations

    • First Department of Internal Medicine, “Hippokratio” General Hospital of Thessaloniki, Thessaloniki, Greece
    • ,
  • Anestis Moumtzouoglou, MD

      Affiliations

    • Department of Radiology, “Hippokratio” General Hospital of Thessaloniki, Thessaloniki, Greece
    • ,
  • Alkistis Kapelouzou, PhD

      Affiliations

    • Center of Experimental Surgery, Biomedical Research Foundation, Academy of Athens, Athens, Greece
    • ,
  • Thomas Gerasimidis, MD

      Affiliations

    • Fifth Surgical Department, Aristotle's University of Thessaloniki, Thessaloniki, Greece
    • ,
  • Christos D. Liapis, MD, FACS, FRCS

      Affiliations

    • Department of Vascular Surgery, Medical School, University of Athens, Athens, Greece

Received 1 June 2009 ,Accepted 31 July 2009.

References 

  1. Ding S, Zhang M, Zhao Y, Chen W, Yao G, Zhang C, et al. The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. Am J Med Sci. 2008;336:27–31
  2. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis (North American Symptomatic Carotid Endarterectomy Trial Collaborators). N Engl J Med. 1998;339:1415–1425
  3. U-King-Im JM, Tang T, Moustafa RR, Baron JC, Warburton EA, Gillard JH. Imaging the cellular biology of the carotid plaque. Int J Stroke. 2007;2:85–96
  4. Heliopoulos J, Vadikolias K, Mitsias P, Artemis D, Tripsianis G, Piperidou C, et al. A three-dimensional ultrasonographic quantitative analysis of non-ulcerated carotid plaque morphology in symptomatic and asymptomatic carotid stenosis. Atherosclerosis. 2008;198:129–135
  5. Nagano K, Yamagami H, Tsukamoto Y, Nagatsuka K, Yasaka M, Nagata I, et al. Quantitative evaluation of carotid plaque echogenicity by integrated backscatter analysis: correlation with symptomatic history and histologic findings. Cerebrovasc Dis. 2008;26:578–583
  6. Reiter M, Effenberger I, Sabeti S, Mlekusch W, Schlager O, Dick P, et al. Increasing carotid plaque echolucency is predictive of cardiovascular events in high-risk patients. Radiology. 2008;248:1050–1055
  7. Kadoglou NP, Gerasimidis T, Golemati S, Kapelouzou A, Karayannacos PE, Liapis CD. The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability. J Vasc Surg. 2008;47:55–62
  8. Kadoglou NP, Gerasimidis T, Moumtzouoglou A, Kapelouzou A, Sailer N, Fotiadis G, et al. Intensive lipid-lowering therapy ameliorates novel calcification markers and GSM score in patients with carotid stenosis. Eur J Vasc Endovasc Surg. 2008;35:661–668
  9. Nakamura T, Obata JE, Kitta Y, Takano H, Kobayashi T, Fujioka D, et al. Rapid stabilization of vulnerable carotid plaque within 1 month of pitavastatin treatment in patients with acute coronary syndrome. J Cardiovasc Pharmacol. 2008;51:365–371
  10. Yamagami H, Sakaguchi M, Furukado S, Hoshi T, Abe Y, Hougaku H, et al. Statin therapy increases carotid plaque echogenicity in hypercholesterolemic patients. Ultrasound Med Biol. 2008;34:1353–1359
  11. Cho HJ, Cho HJ, Kim HS. Osteopontin: a multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification. Curr Atheroscler Rep. 2009;11:206–213
  12. Kiechl S, Werner P, Knoflach M, Furtner M, Willeit J, Schett G. The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease. Expert Rev Cardiovasc Ther. 2006;4:801–811
  13. Ren MY, Sui SJ, Zhang Y, Xu FY, Xu XQ, Zhao JJ, et al. Increased plasma osteoprotegerin levels are associated with the presence and severity of acute coronary syndrome. Acta Cardiol. 2008;63:615–622
  14. Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP. Pleiotropic effects of statins–clinical evidence. Curr Pharm Des. 2009;15:479–489
  15. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. CARDS investigators Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685–696
  16. Dembowski E, Davidson MH. A review of lipid management in primary and secondary prevention. J Cardiopulm Rehabil Prev. 2009;29:2–12
  17. Liapis CD, Bell PR, Mikhailidis D, Sivenius J, Nicolaides A, Fernandes e Fernandes J, et al. ESVS Guidelines Collaborators ESVS guidelines (Invasive treatment for carotid stenosis: indications, techniques). Eur J Vasc Endovasc Surg. 2009;37(4 Suppl):1–19
  18. Kadoglou NP, Iliadis F, Angelopoulou N, Sailer N, Fotiadis G, Voliotis K, et al. Cardiorespiratory capacity is associated with favourable cardiovascular risk profile in patients with Type 2 diabetes. J Diabetes Complications. 2009;23:160–166
  19. Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis–Society of Radiologists in Ultrasound Consensus Conference. Radiology. 2003;229:340–346
  20. Griffiths GD, Razzaq R, Farrell A, Ashleigh R, Charlesworth D. Variability in measurement of internal carotid artery stenosis by arch angiography and duplex ultrasonography–time for a reappraisal?. Eur J Vasc Endovasc Surg. 2001;21:130–136
  21. Rotstein AH, Gibson RN, King PM. Direct B-mode NASCET-style stenosis measurement and Doppler ultrasound as parameters for assessment of internal carotid artery stenosis. Australas Radiol. 2002;46:52–56
  22. Athyros VG, Kakafika AI, Tziomalos K, Papageorgiou AA, Karagiannis A. Statins for the prevention of first or recurrent stroke. Curr Vasc Pharmacol. 2008;6:124–133
  23. Tikkanen MJ, Holme I, Cater NB, Szarek M, Faergeman O, Kastelein JJ, et al. Incremental DEcrease through Aggressive Lipid Lowering Investigators (Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged <65 versus >or=65 years with coronary heart disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] study)). Am J Cardiol. 2009;103:577–582
  24. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711–1718
  25. Amarenco P, Benavente O, Goldstein LB, Callahan A, Sillesen H, Hennerici MG, et al. Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke. 2009;40:1405–1409
  26. Sillesen H, Amarenco P, Hennerici MG, Callahan A, Goldstein LB, Zivin J, et al. Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2008;39:3297–3302
  27. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. REVERSAL Investigators Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–1080
  28. Yu CM, Zhang Q, Lam L, Lin H, Kong SL, Chan W, et al. Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal-medial thickness in patients with coronary heart disease. Heart. 2007;93:933–939
  29. 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
  30. Kostapanos MS, Milionis HJ, Elisaf MS. An overview of the extra-lipid effects of rosuvastatin. J Cardiovasc Pharmacol Ther. 2008;13:157–174
  31. Leali D, Moroni E, Bussolino F, Presta M. Osteopontin overexpression inhibits in vitro re-endothelialization via integrin engagement. J Biol Chem. 2007;282:19676–19684
  32. Golledge J, McCann M, Mangan S, Lam A, Karan M. Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis. Stroke. 2004;35:1636–1641
  33. Ohmori R, Momiyama Y, Taniguchi H, Takahashi R, Kusuhara M, Nakamura H, et al. Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis. 2003;170:333–337
  34. Tanaka N, Momiyama Y, Ohmori R, Yonemura A, Ayaori M, Ogura M, et al. Effect of atorvastatin on plasma osteopontin levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2006;26:e129–e130
  35. Takemoto M, Kitahara M, Yokote K, Asaumi S, Take A, Saito Y, et al. NK-104, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces osteopontin expression by rat aortic smooth muscle cells. Br J Pharmacol. 2001;133:83–88
  36. Sandberg WJ, Yndestad A, Øie E, Smith C, Ueland T, Ovchinnikova O, et al. Enhanced T-cell expression of RANK ligand in acute coronary syndrome: possible role in plaque destabilization. Arterioscler Thromb Vasc Biol. 2006;26:857–863
  37. Omland T, Ueland T, Jansson AM, Persson A, Karlsson T, Smith C, et al. Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes. J Am Coll Cardiol. 2008;51:627–633
  38. Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation. 2004;109:2175–2180
  39. Ben-Tal Cohen E, Hohensinner PJ, Kaun C, Maurer G, Huber K, Wojta J. Statins decrease TNF-alpha-induced osteoprotegerin production by endothelial cells and smooth muscle cells in vitro. Biochem Pharmacol. 2007;73:77–83
  40. Nellemann B, Gormsen LC, Dollerup J, Schmitz O, Mogensen CE, Rasmussen LM, et al. Simvastatin reduces plasma osteoprotegerin in type 2 diabetic patients with microalbuminuria. Diabetes Care. 2007;30:3122–3124

 Competition of interest: none.

 The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest.

PII: S0741-5214(09)01615-2

doi: 10.1016/j.jvs.2009.07.119

Journal of Vascular Surgery
Volume 51, Issue 1 , Pages 114-121 , January 2010

Article Tools

* Image Usage & Resolution