Ten years follow-up under atorvastatin therapy of patients with carotid artery stenosis: the prognostic impact of oxidised low-density lipoprotein on carotid plaque progression and restenosis. Atorvastatin and oxidized LDL in carotid artery stenosis

PDF
Published: Jun 24, 2022
DOI: https://doi.org/10.12681/jhcvm.30181
Keywords:
carotid stenosis oxidize LDL atorvastatin angioplasty atheromatosis
Adamantia Polydorou
1Onassis Cardiac Surgery Center, Echo division, Piraeus, Greece
Konstantinos Alexopoulos
2Department of Anatomy, National and Kapodestrian University of Athens, School of Health Sciences, Faculty of Medicine, Athens, Greece.
Victoria Polydorou
3School of Medicine, European University Cyprus, Nicosia, Cyprus.
Elias Skopelitis
4 2nd Department of Internal Medicine, General Hospital of Nikaia and Piraeus, Athens";}
Xanthula Κougiali
5Biochemistry Laboratory, General Hospital of Nikaia and Piraeus, Greece.
Nikolaos Liasis
6Affidea Medical Centre, Echo division Athens Greece. 7Vascular screening and diagnostic Centre. Nicosia, Cyprus
Theano Demesticha
2Department of Anatomy, National and Kapodestrian University of Athens, School of Health Sciences, Faculty of Medicine, Athens, Greece.
Maria Piagkou
2Department of Anatomy, National and Kapodestrian University of Athens, School of Health Sciences, Faculty of Medicine, Athens, Greece.
Vasilios Protogerou
2Department of Anatomy, National and Kapodestrian University of Athens, School of Health Sciences, Faculty of Medicine, Athens, Greece.
Dimitris Filippou
2Department of Anatomy, National and Kapodestrian University of Athens, School of Health Sciences, Faculty of Medicine, Athens, Greece.
Eleni Velissariou
8Medical Genetics, Queen Mary University, London, UK.
George Dimakopulos
9BIOSTATS, Epirus Science and Technology Park, Campus of the University of Ioannina, Ioannina, Greece
Theodoros Troupis
2Department of Anatomy, National and Kapodestrian University of Athens, School of Health Sciences, Faculty of Medicine, Athens, Greece.
Abstract

Background: Atorvastatin reduces oxidized low-density lipoprotein (oxLDL) levels and reduces the rate of plaque progression in patients with and without prior carotid angioplasty. The aim of our study was to investigate the durability of this effect and to explore possible prognostic impact of oxLDL levels on carotid stenosis and plaque stability.


            Methods: 106 patients (71 males, mean age 64.82±7.26 years) were studied. They were divided into two groups. Group 1 including patients with carotid stenosis >70% (n=50) who underwent carotid angioplasty prior to enrolment. Group 2 included those with <70% stenosis who were treated medically and were given atorvastatin with dose adjusted to maintain LDL cholesterol <100mg/dl. Anthropometrics, complete lipid profile, oxLDL and ultrasonography were performed at baseline, 1, 3, 6, 12 months and yearly thereafter for 10 years.


            Results: oxLDL levels significantly decreased from 53.3±10.91 mg/dl at baseline to 8.31±2.08 mg/dl at 12 months (p<0.001) and remained stable until the 10th year. In group 1, restenosis (>70%) was noticed in four patients, yet no further intervention was needed due to plaque morphology (echo-grade IV). In group 2, carotid stenosis was initially reduced (6th month – 4th year) and later relapsed (5th – 10th year), yet plaque morphology was recorded as type III or IV in almost all patients of group 2 (53=95%), indicating a significantly lower risk for stroke.


            Conclusion: Atorvastatin treatment to a target of LDL <100 mg/dl in patients with carotid stenosis is associated with marked and durable reduction of lipid levels, especially oxLDL and LDL and reduction in the rate of stenosis progression, improved plaque stability and decreased stroke risk.

Article Details
  • Section
  • Articles
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

  This work is licensed under a [Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License|https://creativecommons.org/licenses/by-nc-sa/4.0/]. Authors who publish with this journal agree to the following terms: # Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a CC-BY-NC-SA that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. # Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g. post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. # Authors are permitted and encouraged to post their work online (preferably in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See [The Effect of Open Access|http://opcit.eprints.org/oacitation-biblio.html]).

Downloads
Download data is not yet available.
References
Toshima S, Hasegawa A, Kurabayashi M, Itabe H, Takano T, Sugano J, et al. Circulating oxidized low density lipoprotein levels. A biochemical risk marker for coronary heart disease. Arterioscler Thromb Vasc Biol 2000;20(10):2243-7.
Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, et al. Elevated
levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001;103(15):1955-60.
Holvoet P, Harris TB, Tracy RP, Verhamme P, Newman AB, Rubin SM, et al. Association of high coronary heart disease risk status with circulating oxidized LDL in the well-functioning elderly: findings from the Health, Aging, and Body Composition study. Arterioscler Thromb Vasc Biol 2003;23(8):1444-8.
Penny WF, Ben-Yehuda O, Kuroe K, Long J, Bond A, Bhargava V, et al. Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasmaoxidized low density lipoprotein. J Am Coll Cardiol 2001;37(3):766-74.
Nishi K, Itabe H, Uno M, Kitazato KT, Horiguchi H, Shinno K, et al.
Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol 2002;22(10):1649-54.
Holvoet P, Collen D, Van de Werf F. Malondialdehyde-modified LDL as a marker of acute coronary syndromes. Jama 1999;281(18):1718-21.
Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D.
Modification of low density lipoprotein by endothelial cells involves lipid
peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A 1984;81(12):3883-7.
Li D, Chen H, Romeo F, Sawamura T, Saldeen T, Mehta JL. Statins
modulate oxidized low-density lipoprotein-mediated adhesion molecule
expression in human coronary artery endothelial cells: role of LOX-1. J Pharmacol Exp Ther 2002;302(2):601-5.
Steinberg D. Low density lipoprotein oxidation and its pathobiological
significance. J Biol Chem 1997;272(34):20963-6.
Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med
;340(2):115-26.
Li DY, Chen HJ, Mehta JL. Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation. Cardiovasc Res 2001;52(1):130-5.
Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related
effects of statins. Ann Med 2000;32(3):164-76.
Giroux LM, Davignon J, Naruszewicz M. Simvastatin inhibits the oxidation of low-density lipoproteins by activated human monocyte-derived macrophages. Biochim Biophys Acta 1993;1165(3):335-8.
Aviram M, Rosenblat M, Bisgaier CL, Newton RS. Atorvastatin and
gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation. Atherosclerosis 1998;138(2):271-80.
Puccetti L, Pasqui AL, Pastorelli M, Bova G, Cercignani M, Palazzuoli A,et al. Time-dependent effect of statins on platelet function in
hypercholesterolaemia. Eur J Clin Invest 2002;32(12):901-8.
Holvoet P, Donck J, Landeloos M, Brouwers E, Luijtens K, Arnout J, et al. Correlation between oxidized low density lipoproteins and von Willebrand factor in chronic renal failure. Thromb Haemost 1996;76(5):663-9.
S Kougialis, E Skopelitis, T Gialernios, S Nikolaou, A Kroustalis, E Katsadorou, K Gialernios, A Zervou, E Gika, A Polydorou, V Polydorou, C Drakoulis, N Iliopoulos, I Dermitzakis, H Mpilinis, A Polydorou. Atorvastatin therapy is associated with improvement of oxidized low-density lipoprotein cholesterol levels, which correlates with the degree of stenosis in patients with carotid atheromatosis with and without prior angioplasty. Int Angiol. 2010 Aug;29(4):338-47.
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(2):340-6.
Executive Summary of The 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). Jama 2001;285(19):2486-97.
van Tits LJ, van Himbergen TM, Lemmers HL, de Graaf J, Stalenhoef AF. Proportion of oxidized LDL relative to plasma apolipoprotein B does not change during statin therapy in patients with heterozygous familial hypercholesterolemia. Atherosclerosis 2006;185(2):307-12.
Liu ML, Ylitalo K, Salonen R, Salonen JT, Taskinen MR. Circulating
oxidized low-density lipoprotein and its association with carotid intima-media thickness in asymptomatic members of familial combined hyperlipidemia families. Arterioscler Thromb Vasc Biol 2004;24(8):1492-7.
Robbesyn F, Salvayre R, Negre-Salvayre A. Dual role of oxidized LDL on the NF-kappaB signaling pathway. Free Radic Res 2004;38(6):541-51.
Hulthe J, Fagerberg B. Circulating oxidized LDL is associated with
subclinical atherosclerosis development and inflammatory cytokines (AIR Study). Arterioscler Thromb Vasc Biol 2002;22(7):1162-7.
Archbold RA, Timmis AD. Modification of coronary artery disease
progression by cholesterol-lowering therapy: the angiographic studies. Curr Opin Lipidol 1999;10(6):527-34.
Bellosta S, Bernini F, Ferri N, Quarato P, Canavesi M, Arnaboldi L, et al. Direct vascular effects of HMG-CoA reductase inhibitors. Atherosclerosis1998;137 Suppl:S101-9.
Weber C, Erl W, Weber KS, Weber PC. HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. J Am Coll Cardiol 1997;30(5):1212-7.
Jarvisalo MJ, Toikka JO, Vasankari T, Mikkola J, Viikari JS, Hartiala JJ, et al. HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease. Atherosclerosis 1999;147(2):237-42.
Rothe G, Herr AS, Stohr J, Abletshauser C, Weidinger G, Schmitz G. A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment in hypercholesterolemic patients with coronary heartdisease. Atherosclerosis 1999;144(1):251-61.
Fuhrman B, Koren L, Volkova N, Keidar S, Hayek T, Aviram M.
Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis 2002;164(1):179-85.
Vasankari T, Ahotupa M, Viikari J, Nuotio I, Vuorenmaa T, Strandberg T, et al. Effects of statin therapy on circulating conjugated dienes, a measure of LDL oxidation. Atherosclerosis 2005;179(1):207-9.
Mason RP, Walter MF, Jacob RF. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation 2004;109(21 Suppl 1):II34-41.
Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, Szarek M, Olsson AG, et al. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial. Circulation 2004;110(11):1406-12.
Mulder DJ, van Haelst PL, Wobbes MH, Gans RO, Zijlstra F, May JF, et al. The effect of aggressive versus conventional lipid-lowering therapy on markers of inflammatory and oxidative stress. Cardiovasc Drugs Ther 2007;21(2):91-7.
Orem C, Orem A, Uydu HA, Celik S, Erdol C, Kural BV. The effects of lipid-lowering therapy on low-density lipoprotein auto-antibodies: relationship with low-density lipoprotein oxidation and plasma total antioxidant status. Coron Artery Dis 2002;13(1):65-71.
Ky B, Burke A, Tsimikas S, Wolfe ML, Tadesse MG, Szapary PO, et al. The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans. J Am Coll Cardiol 2008;51(17):1653-62.
Sakabe K, Fukuda N, Wakayama K, Nada T, Shinohara H, Tamura Y. Effects of atorvastatin therapy on the low-density lipoprotein subfraction,
remnant-like particles cholesterol, and oxidized low-density lipoprotein within 2 weeks in hypercholesterolemic patients. Circ J 2003;67(10):866-70.
Miyagishima K, Hiramitsu S, Kato S, Kato Y, Kitagawa F, Teradaira R, et al. Efficacy of atorvastatin therapy in ischaemic heart disease - effects on oxidized low-density lipoprotein and adiponectin. J Int Med Res 2007;35(4):534-9.