MANAGEMENT OF THE CAROTID ARTERY STENOSIS IN ASYMPTOMATIC PATIENTS
DOI:
https://doi.org/10.48729/pjctvs.25Abstract
Background: An asymptomatic carotid stenosis (CS) is defined as a stable atherosclerotic luminal narrowing in patients with no history of ipsilateral cerebral or ocular ischemic events in the past six months. The bifurcation of the common carotid artery makes this area vulnerable to atherosclerosis due to the features of haemodynamic flow. The exact prevalence of asymptomatic patients with CS remains unknown and opinions on the treatment of these patients are controversial.
Objective: The authors aimed to review the evidence on the management of the asymptomatic CS and describe its clinical characteristics, diagnosis and treatment management.
Methods: A comprehensive review of the literature was carried out to collate data from relevant studies concerning patients with extracranial moderate to severe asymptomatic carotid stenosis. The data used was identified by a search using PubMed and Google Scholar with the keywords / MESH terms "carotid stenosis", in combination with the term "asymptomatic". For this study, the authors focused on publications in the past two decades, using English publications.
Results: A few studies have addressed the prevalence, natural course and/or prognostic impact of asymptomatic CS in patients under medical treatment or undergoing vascular surgery procedures. The prevalence of asymptomatic CS ranged from 0.3% to 4.5% in women and 0.5% to 5.7% in men - The risk of stroke/TIA in these patients was reported between 2% to 5% annually with a downward trend across time to 0.5% with current best medical therapy.
Conclusion: A great proportion of patients with asymptomatic CS should be submitted to conservative management with best medical therapy. However, selective surgical management should be considered if high risk features are present.
Downloads
References
Silva ENF d. Doença Vascular Cerebral Extracraniana – critérios de tratamento médico e cirúrgico, in Angiologia e Cirurgia Vascular.
Nichols M, Townsend N, Luengo-Fernandez R, Leal J, Scarborough P RM. European cardiovascular disease statistics. Eur Hear Netw Eur Soc Cardiol. 2012.
AR. Naylor, Why is the management of asymptomatic carotid disease so controversial? Surg. 2015:34,43.
M. de Weerd, J.P. Greving, B. Hedblad, M.W. Lorenz, E.B. Mathiesen, D.H. O’Leary, , M. Rosvall, M. Sitzer, E. Buskens and MLB. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis. Stroke. 2010;41:1294-1297.
Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RK, Meldrum HE BH. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. N Engl J Med. 2000;342:1693–1700.
Hennerici M, Hulsbomer HB, Hefter H, Lammerts D RW. Natural history of asymptomatic extracranial arterial disease: results of a long-term prospective study. Brain. 1987;110:777–791.
Norris JW, Zhu CZ, Bornstein NM CB. Vascular risks of asymptomatic carotid stenosis. Stroke. 1991;22:1485–1490.
O’Holleran LW, Kennelly MM, McClurken M JJ. Natural history of asymptomatic carotid plaque: five year follow-up study. Am J Surg. 1987;154:659–662.
Lal. BK. Carotid artery stenosis. BMJ Best Pract. 2019.
Autret A, Pourcelot L, Saudeau D, Marchal C, Bertrand P de BS. Stroke risk in patients with carotid stenosis. Lancet. 1987:888–890.
Prasad K. Pathophysiology and Medical Treatment of Carotid Artery Stenosis. Int J Angiol. 2015;24:158–172.
Inês Müller Pinheiro, Gil Marques, Nádia Duarte, Ana Gonçalves, Pedro Barroso, António Gonzalez MJF. Patologia da carótida. Rev Port Clin Geral. 2010;26:496-501.
Jacob Fog Bentzon, Fumiyuki Otsuka, Renu Virmani and EF. Mechanisms of Plaque Formation and Rupture. Circ Res. 2014;114:1852–1866.
Mauriello A, Sangiorgi G M VR et al. A pathobiologic link between risk factors profile and morphological markers of carotid instability. Atherosclerosis. 2010;208:572–580.
Prasad K KJ. Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E. Am Hear J. 1993;125:958–973.
K. Prasad. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation. 1999;99:1355–1362.
Willam C, Schindler R, Frei U EKU. Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells. Am J Physiol. 1999;276:2044–2052.
Chiu J J, Wung B S, Shyy J Y-J, Hsieh H J WDL. Reactive oxygen species are involved in shear stress-induced intercellular adhesion molecule-1 expression in endothelial cells. Arter Thromb Vasc Biol. 1997;17:3570–3577.
Cushing S D, Berliner J A VAJ et al. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci U S A. 1990;87:5134–5138.
Rajagopalan S, Meng X P, Ramasamy S, Harrison D G GZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 1996;98:2572–2579.
Ajoe John Kattoor, Jawahar L. Mehta. Oxidative Stress in Atherosclerosis. Genet Genomics. 2017;42.
Phan S H, McGarry B M, Loeffler K M KSL. Regulation of macrophage- derived fibroblast growth factor release by arachidonate metabolites. J Leukoc Biol. 1987;42:106–113.
Yamazaki M US. Pathophysiology of carotid stenosis. Brain Nerve. 2010;62:1269–1275.
Yung-Chih Chen, Alex L. Huang, Tin S. Kyaw, Alex Bobik and KP. Atherosclerotic Plaque Rupture. Arterioscler Thromb Vasc Biol. 2016.
Ronald M. Fairman. Management of asymptomatic carotid atherosclerotic disease. UpToDate. https://www.uptodate.com/contents/management-of-asymptomatic-carotid-atherosclerotic-disease
Jack N. Alpert. Extracranial carotid artery. Current concepts of diagnosis and management. Texas Heart Inst J. 1991;18:93–97.
Audrey Bowen, Martin James GY. National Clinical Guideline for stroke. R Coll Physicians. Fifth edition, 2016.
Mathiesen E B, Joakimsen O BKH. Prevalence of and risk factors associated with carotid artery stenosis: the Tromsø Study. Cerebrovasc Dis. 2001;12:44– 51.
de Weerd M, Greving JP, Hedblad B, Lorenz MW, Mathiesen EB, O’Leary DH et al. Prediction of asymptomatic carotid artery stenosis in the general population identification of high-risk groups. Stroke. 2014;45:2366-2371.
Prasad K. Pathophysiology of atherosclerosis. New York, NY Springer Verlag. 2000:85-105.
O’Donnell R W, Johnson D K, Ziegler L M, DiMattina A J, Stone R I HJA. Endothelial NADPH oxidase: mechanism of activation by low-density lipoprotein. Endothelium. 2003;10:291–297.
Amarenco P LJ. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009:453-463.
Kim Y S, Sung H J SSJ et al. Triglyceride (TG) down-regulates expression of MCP-1 and CCR2 in PMA-derived THP-1 macrophages. Genes and Genomics. 2013;35:125–130.
Bautista L E, Vera L M, Arenas I A GG. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension. J Hum Hypertens. 2005;19:149–154.
Shalia K K, Mashru M R, Vasvani J B, Mokal R A, Mithbawkar S M TPK. Circulating levels of cell adhesion molecules in hypertension. Indian J Clin Biochem. 2009;24:388–397.
Aldons J. Lusis. Atherosclerosis. Nature. 2000;407:233–241.
Kitiyakara C WCS. Antioxidants for hypertension. Curr Opin Nephrol Hypertens. 1998;7:531–538.
Mast H, Thompson J LP LI-F et al. Cigarette smoking as a determinant of high- grade carotid artery stenosis in Hispanic, black, and white patients with stroke or transient ischemic attack. Stroke. 1998;29:908–912.
Kalra J, Chaudhary A K PK. Increased production of oxygen free radicals in cigarette smokers. Int J Exp Pathol. 1991;72:1-7.
Nicholl I D BR. Advanced glycation endproducts and cigarette smoking. Cell Mol Biol. 1998;44:1025–1033.
K. P. Soluble receptor for advanced glycation end products (sRAGE) and cardiovascular disease. Int J Angiol. 2006;15:57–68.
Bonnefont-Rousselot. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care. 2002;5:561–568.
Inoguchi T, Li P UF et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C—dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49:1939–1945.
Xia P, Inoguchi T, Kern T S, Engerman R L, Oates P J KGL. Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes. 1994;43:1122–1129.
Zachary T. Bloomgarden. Obesity and diabetes. Diabetes Care. 2000;23:1584–1590.
Kotsis V, Stabouli S, Papakatsika S, Rizos Z PG. Mechanisms of obesity- induced hypertension. Hypertens Res. 2010;33:386–393.
Kailash Prasad. C-reactive protein increases oxygen radical generation by neutrophils. J Cardiovasc Pharmacol Ther. 2004;9:203–209.
Kailash Prasad. C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev. 2006;24:33–50.
Ringer A. Carotid stenosis (carotid artery disease). Mayfield, Brain and Spine. MayfieldClinic.com.https://d3djccaurgtij4.cloudfront.net/pe-carotidstenosis.pdf
Anxin Wang, Lingyun Wu, et al. The prevalence of carotid plaque with different stability and its association with metabolic syndrome in China. Medicine (Baltimore). 2016; 95(34): e4619.
Kakkos SK, Nicolaides AN, Charalambous I, Thomas D, Giannopoulos A, Naylor AR, Geroulakos G A AL. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis. J Vasc Surg. 2014:956-967.
Perren F. Carotid artery stenosis grading and examination of the vulnerable plaque. 3rd Congr Eur Acad Neurol. 2017.
A.R. Naylor, J.-B. Riccoa, G.J. de Bors et al. Editor’s Choice – Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018;55:3-81.
Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160–2236.
Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J med. 2013;368:1279–1290.
Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J am Coll Cardiol. 2014;63:2960–2984.
Sacco RL, Adams R, Albers G et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American StrokeAssociation Council on Stroke: Co-sponsored by the Council on Ca. Stroke. 2006;37:577-617.
Sacks FM, Svetkey LP, Vollmer WM et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3–10.
Chiuve SE, Rexrode KM, Spiegelman D et al. Primary prevention of stroke by healthy lifestyle. Circulation. 2008;118:947–54.
de Lorgeril M, Salen P, Martin J-L et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999;99:779–85.
Naylor AR. Expert commentary on asymptomatic carotid stenosis less is more! Indian J Vasc Endovasc Surg. 2018;5:6-8.
Barnett H J, Taylor D W EM 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.
Study EC for the ACA. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273:1421–1428.
John J. Ricotta et al. Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease. J Vasc Surg. 2011;54:1-31.
Hobson R W II, Mackey W C AE et al. Management of atherosclerotic carotid artery disease: clinical practice guidelines of the Society for Vascular Surgery. J Vasc Surg. 2008;48:480–486.
Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J et al. 10- year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010;376:1074-1084.
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278.
Law MR, Morris JK WN. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:1665.
Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF et al. CSPPT Investigators. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015;313:1325–1335.
Bryan Williams, Giuseppe Mancia, Wilko Spiering, Enrico Agabiti Rosei, Michel Azizi, Michel Burnier, Denis L Clement, Antonio Coca, Giovanni de Simone AD. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104.
Rothwell PM GL. Carotid endarterectomy for Asymptomatic Carotid Surgery Trial. Stroke. 2004;35:2425-2427.
Halliday A, Mansfield A, Marro J et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363:1491- 1502.
Nicolaides AN, Kakkos SK, Griffin M et al. Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study. Eur J Vasc Endovasc Surg. 2005;30:275-284.
Plenge J K, Hernandez T L WKM et al. Simvastatin lowers C-reactive protein within 14 days: An effect independent of low density lipoprotein cholesterol reduction. Circulation. 2002;106:1447–1452.
LS. H. Progression rate and ipsilateral neurological events in asymptomatic carotid stenosis. Stroke. 2014;45:702-706.
Nicolaides AN, Kakkos SK, Kyriacou E et al. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. J Vasc Surg. 2010;52:1486-1496.
Madani A, Beletsky V, Tamayo A, Munoz C, Spence JD et al. High-risk asymptomatic carotid stenosis: ulceration on 3D ultrasound vs TCD microemboli. Neurology. 2011;77:744-750.
Mitchell C, Korkarz C, Gepner A, Nye R, Young R, Matsuzaki M, Post W, Kaufman J, McClelland R, Stein J. Carotid Artery Echolucency, Texture Features, and Incident Cardiovascular Disease Events: The MESA Study. J. Am. Heart Assoc. 2019; 8(3): e010875
Paraskevas KI, Spence JD, Veith FJ, Nicolaides AN et al. Identifying which patients with asymptomatic carotid stenosis could benefit from intervention. Stroke. 2014;45:3720-3724.
Abbott AL, Chambers BR, Stork JL, Levi CR, Bladin CF DG. Embolic signals and prediction of ipsilateral stroke or transient ischemic attack in asymptomatic carotid stenosis: a multicenter prospective cohort study. Stroke. 2005;36:1128- 1133.
Gupta A, Chazen JL, Hartman M et al. Cerebrovascular reserve and stroke risk in patients with carotid stenosis or occlusion: a systematic review and meta- analysis. Stroke. 2012;43:2884-2891.
Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:3754-3832.
Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:517-584.
J David Spence, Hongsong Song GC. Appropriate management of asymptomatic carotid stenosis. BMJ. 2016;1.
Selim M H MCA. Medical versus surgical treatment of asymptomatic carotid stenosis: the ever-changing nature of evidence-based medicine. Stroke. 2011;42:1156–1157.
Kamal Gupta ZS. What Is the Future of Asymptomatic Carotid Artery Disease? Am Coll Cardiol. Jun 16, 2015.
