The role of inflammation is well established in the pathogenesis of atherosclerosis and an increased level of circulating inflammatory markers may predict the future risk of atherosclerosis progression and plaque rupture. C-reactive protein (CRP) identification by hypersensitive methods (high-sensitivity CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid endarterectomy (CEA) is a well-established procedure for carotid stenosis treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis reduction may be prevented by the anti-inflammatory effect of statins. This review considers the recent findings on the presence of hsCRP and C3 complement concentration and inflammatory plaque composition as well as their effects on ICA restenosis rate, following eversion CEA with emphasis on human studies.
LiJJFangCH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses. 2004;62(4):499–506.
2.
RossR. Atherosclerosis is an inflammatory disease. Am Heart J. 1999;138(5 pt 2):S419–S420.
3.
DósaERugonfalvi-KissSProhászkaZ. Marked decrease in the levels of two inflammatory markers, hs-C-reactive protein and fibrinogen in patients with severe carotid atherosclerosis after eversion carotid endarterectomy. Inflamm Res. 2004;53(11):631–635.
4.
LibbyP. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–874.
5.
VermaSBuchananMRAndersonTJ. Endothelial function testing as a biomarker of vascular disease. Circulation. 2003;108(17):2054–2059.
6.
RidkerPMRifaiNRoseLBuringJECookNR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557–1565.
7.
RidkerPMHennekensCHBuringJERifaiN. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(20):836–843.
8.
RidkerPM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107(3):363–369.
9.
VermaSLiSHBadiwalaMV. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation. 2002;105(16):1890–1896.
10.
VermaSWangCHLiSHDumontASFedakPWBadiwalaMV. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation. 2002;106(8):913–919.
11.
PasceriVChengJSWillersonJTYehET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation. 2001;103(21):2531–2534.
12.
PasceriVWillersonJTYehET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102(18):2165–2168.
13.
ZwakaTPHombachVTorzewskiJ. C-reactive protein-mediated low-density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation. 2001;103(9):1194–1197.
14.
WangCHLiSHWeiselRD. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation. 2003;107(13):1783–1790.
15.
VermaSLiSHWangCH. Hyperglycemia potentiates the proatherogenic effects of C-reactive protein: reversal with rosiglitazone. J Mol Cell Cardiol. 2003;35(4):417–419.
16.
VermaSKuliszewskiMALiSH. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation. 2004;109(17):2058–2067.
17.
YehETWillersonJT. Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation. 2003;107(3):370–371.
18.
VenugopalSKDevarajSYuhannaIShaulPJialalI. Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation. 2002;106(12):1439–1441.
19.
DevarajSXuDYJialalI. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation. 2003;107(3):398–404.
20.
LiuzzoGBiasucciLMRebuzziAGGallimoreJRLanzaAGQuarantaG. Plasma protein acute-phase response in unstable angina is not induced by ischemic injury. Circulation. 1996;94(10):2373–2380.
21.
ParaskevasKIBessiasNPapasTTAndrikopoulosVMikhailidisDP. Is high-sensitivity C-reactive protein associated with subclinical peripheral atherosclerosis?. Angiology. 2009;60(1):8–11.
22.
ParaskevasKIMikhailidisDPVeithFJ. Mechanisms to explain the poor results of carotid artery stenting (CAS) in symptomatic patients to date and options to improve CAS outcomes. J Vasc Surg. 2010;52(5):1367–1375.
23.
NASCETInvestigators. Clinical alert: benefit of carotid endarterectomy for patients with high-grade stenosis of the internal carotid artery. National Institute of Neurological Disorders and Stroke, Stroke and Trauma Division. North American Symptomatic Carotid Endarterectomy Trial. Stroke. 1991;22(6):816–817.
24.
LiapisCDBellPFMikhailidisDP. ESVS Guidelines Collaborators; European Society for Vascular Surgery. ESVS Guidelines: Section A-prevention in patients with carotid stenosis. Curr Vasc Pharmacol. 2010;8(5):673–681.
25.
SchillingerMExnerMMlekuschW. Acute-phase response after stent implantation in the carotid artery: association with 6-month in-stent restenosis. Radiology. 2003;227(2):516–521.
26.
SzmitkoPEWangC-HWeiselRDde AlmeidaJRAndersonTJVermaS. New markers of inflammation and endothelial cell activation Part I. Circulation. 2003;108(16):1917–1923.
27.
Gottsauner-WolfMZasmetaGHornykewyczS. Plasma levels of C-reactive protein after coronary stent implantation. Eur Heart J. 2000;21(14):1152–1158.
28.
FusterVFalkEFallonJTBadimonLChesebroJHBadimonJJ. The three processes leading to post PTCA restenosis: dependence on the lesion substrate. Thromb Haemost. 1995;74(1):552–559.
29.
RidkerPMCushmanMStampferMJTracyRP. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336(14):973–979.
30.
HaverkateFThompsonSGPykeSDMGallimoreJRPepysMB. Production of C-reactive protein and risk of coronary events in stable and unstable patients. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet. 1997;349(9050):462–466.
31.
TossHLindhalBSiegbahnAWallentinL. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in coronary artery disease. Circulation. 1997;96(12):4204–4210.
32.
DoggenCJMBerckmansRJSturkAMangerVRosendaalFR. C-reactive protein, cardiovascular risk factors and the association with myocardial infarction in men. J Intern Med. 2000;248(5):406–414.
33.
RidkerPMCushmanMStampferMJTracyRPHennekensCH. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998;97(5):425–428.
34.
Van ExelEGusseklovJde CraenAJMBootsma van der WielAFrolichMWestendorpRGJ. Inflammation and stroke: the Leiden 85-Plus Study. Stroke. 2002;33(4):1135–1138.
35.
Di NapoliMPapaFBocolaV. Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke. 2001;32(1):133–138.
36.
MuirKWWeirCJAlwanWSquireIBLeesKR. C-reactive protein and outcome after ischemic stroke. Stroke. 1999;30(5):981–985.
YehETWillersonJT. Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation. 2003;107(3):370–371.
39.
PearsonTAMensahGAAlexanderRW. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107(3):499–511.
40.
BuffonALiuzzoGBiasucciLM. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol. 1999;34(5):1512–1521.
41.
AngioiMAbdelmouttalebIRodriguezRM. Increased C-reactive protein levels in patients with in-stent restenosis and its implications. Am J Cardiol. 2001;87(10):1189–1193.
42.
DibraAMehilliJBraunS. Association between C-reactive protein levels and subsequent cardiac events among patients with stable angina treated with coronary artery stenting. Am J Med. 2003;114(9):715–722.
43.
de WinterRJKochKTvan StraalenJP. C-reactive protein and coronary events following percutaneous coronary angioplasty. Am J Med. 2003;115(2):85–90.
44.
AndersonJLMuhlesteinJB. Restenosis after coronary intervention: narrowing C-reactive protein’s prognostic potential?. Am J Med. 2003;115(2):147–149.
45.
OtsukaMHayashiYUedaHImazuMKohnoN. Predictive value of preprocedural fibrinogen concerning coronary stenting. Atherosclerosis. 2002;164(2):371–378.
46.
Van Der MeerIde MaatMPHakAE. C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study. Stroke. 2002;33(12):2750–2755.
47.
Alvarez GarciaBRuizCChaconPSabinJAMatasM. High-sensitivity C-reactive protein in high-grade carotid stenosis: risk marker for unstable carotid plaque. J Vasc Surg. 2003;38(5):1018–1024.
48.
HunterGC. Edgar J, Poth Memorial/WL Gore and Associates, Inc. Lectureship. The clinical and pathological spectrum of recurrent carotid stenosis. Am J Surg. 1997;174(6):583–588.
49.
FrericksHKievitJvan BaalenJMvan BockelJH. Carotid recurrent stenosis and risk of ipsilateral stroke: a systematic review of the literature. Stroke. 1998;29(1):244–250.
50.
ZierlerREBandykDFThieleBLStrandnessDEJr. Carotid artery stenosis following endarterectomy. Arch Surg. 1982;117(11):1408–1415.
51.
RicottaJJO'BrienMSDeWeeseJA. Natural history of recurrent and residual stenosis after carotid endarterectomy: implications for postoperative surveillance and surgical management. Surgery. 1992;112(4):656–661.
52.
TrisalVPaulsonTHansSSMittalV. Carotid artery restenosis: an ongoing disease process. Am Surg. 2002;68(3):275–279.
53.
Rugonfalvi-KissSDósaEMadsenHO. High rate of early restenosis after carotid eversion endarterectomy in homozygous carriers of the normal mannose-binding lectin genotype. Stroke. 2005;36(5):944–948.
54.
SzéplakiGVargaLLakiJ. Elevated complement C3 is associated with early restenosis after eversion carotid endarterectomy. Thromb Haemost. 2006;96(4):529–534.
55.
TelmanGKouperbergEHlebtovskyA. Embolic potential and ultrasonic characteristics of plaques in patients with severe unilateral carotid restenosis more than one year after surgery. J Neur Sci. 2009;285(1-2):85–87.
56.
MakiharaNTozodaKUdaK. Characteristic sonoraphic findings of early restenosis after carotid endarterectomy. J Ultrasound Med. 2008;27(9):1345–1352.
57.
MalekAMalekAKLeszczynskiJ. Carotid clamping time as a risk factor for early restenosis after carotid endarterectomy. Eur J Vasc Endovasc Surg. 2005;30(2):143–146.
58.
HellingsWEMollFLDe VriesJPAckerstaffRGSeldenrijkKAMetR. Atherosclerotic plaque composition and occurrence of restenosis after carotid endarterectomy. J Vasc Surg. 2008;299(5):547–554.
59.
ParaskevasKIMikhailidisDPLiapisCD. Internal carotid artery occlusion: association with atherosclerotic disease in other arterial beds and vascular risk factors. Angiology. 2007;58(3):329–335.
60.
BalkEMLauJGoudasLC. Effects of statin non-lipid serum markers associated with cardiovascular disease. Ann Intern Med. 2003;139(8):670–682.
61.
NagilaAPermpongpaiboonTTantrarongrojS. Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status. Pharmacol Rep. 2009;61(5):892–898.
62.
KassanMMonteroMJSevillaMA. In vitro antioxidant activity of pravastatin provides vascular protection. Eur J Pharmacol. 2010;630(1-3):107–111.
63.
TsimihodimosVKostoulaAKakafikaA. Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. J Cardiovasc Pharmacol Ther. 2004;9(1):27–33.
64.
BelfortRBerriaRCornellJCusiK. Fenofibrate reduces systemic inflammation markers independent of its effects on lipid and glucose metabolism in patients with the metabolic syndrome. J Clin Endocrinol Metab. 2010;95(2):829–836.
65.
TziomalosKKakafikaAIAthyrosVGKaragiannisAMikhailidisDP. The role of statins for the primary and secondary prevention of coronary heart disease in women. Curr Pharm Des. 2009;15(10):1054–1062.
66.
AthyrosVGKakafikaAITziomalosKKaragiannisAMikhailidisDP. Pleiotropic effects of statins—clinical evidence. Curr Pharm Des. 2009;15(5):479–489.
67.
ParaskevasKIStathopoulosVMikhailidisDP. Pleiotropic effects of statins: implications for a wide range of diseases. Curr Vasc Pharmacol. 2008;6(4):237–239.
68.
KoutouzisMParaskevasKIRallidisLS. Statin treatment, carotid atherosclerotic plaque macrophage Infiltration and circulating inflammatory markers. Open Cardiovasc Med J. 2008;2:110–114.
69.
RidkerPMRifaiNPfefferMASacksFBraunwaldE. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100(3):230–235.
70.
RidkerPMRifaiNPfefferMA. Inflammation, pravastatin and the risk of coronary events after mzocardial infacrtion in patients with average cholesterol levels. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1998;98(9):839–844.
71.
RidkerPMDanielsonEFonsecaFAH. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–2207.
72.
HlatkyM. Expanding the orbit of primary prevention—moving beyond JUPITER [editorial]. N Engl J Med. 2008;359(21):2280–2282.
73.
ZachoJTybjærg-HansenAJensenJS. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008;359(18):1897–1908.
74.
BreimerLHMikhailidisDP. Primary prevention using statins: to be or not to be?. Curr Med Res Opin. 2010;26(11):2701–2706.
75.
[No authors listed]A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348(9038):1329–1339.
76.
ChewDPBhattDLRobbinsMA. Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein. Am J Cardiol. 2001;88(6):672–674.
77.
IijimaRByrneRANdrepepaG. Pre-procedural C-reactive protein levels and clinical outcomes after percutaneous coronary interventions with and without abciximab: pooled analysis of four ISAR trials. Heart. 2009;95(2):107–112.
78.
RidkerPMRifaiNPfefferMASacksFBraunwaldE. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100(3):230–235.
79.
AlbertMADanielsonERifaiNRidkerPM. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. J Am Med Assoc. 2001;286(1):64–70.
80.
RidkerPMRifaiNLowenthalSP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation. 2001;103(9):1191–1193.
81.
WagnerDDBurgerPC. Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol. 2003;23(12):2131–2137.
82.
WeyrichASLindemannSZimmermanGA. The evolving role of platelets in inflammation. J Thromb Haemost. 2003;1(9):1897–1905.
83.
IkonomidisIAndreottiFEconomouEStefanadisCToutouzasPNihoyannopoulosP. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation. 1999;100(8):793–798.
84.
KlinkhardtUBauersachsRAdamsJGraffJLindhoff-LastEHarderS. Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther. 2003;73(3):232–241.
85.
VavuranakisMLatsiosGAggelisD. Randomized comparison of the effects of ASA plus clopidogrel versus ASA alone on early platelet activation in acute coronary syndromes with elevated high-sensitivity C-reactive protein and soluble CD40 ligand levels. Clin Ther. 2006;28(6):860–871.
86.
QuinnMJBhattDLZidarF. Effect of clopidogrel pretreatment on inflammatory marker expression in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2004;93(6):679–684.
87.
KreutzRPTantryUSBlidenKPGurbelPA. Inflammatory changes during the ‘common cold’ are associated with platelet activation and increased reactivity of platelets to agonists. Blood Coagul Fibrinolysis. 2007;18(8):713–718.
88.
ModicaAKarlssonFMooeT. Platelet aggregation and aspirin nonresponsiveness increase when an acute coronary syndrome is complicated by an infection. J Thromb Haemost. 2007;5(3):507–511.
89.
CanavanBSalemROSchurginS. Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation. J Clin Endocrinol Metab. 2005;90(10):5779–5785.
90.
SimonTVerstuyftCMary-KrauseM. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360(4):363–375.
91.
RadakDJIlijevskiNSNenezicD. Temporal trends in eversion carotid endarterectomy for carotid atherosclerosis: single-center experience with 5,034 patients. Vascular. 2007;15(4):205–210.
92.
RadakDTanaskovicSIlijevskiN. Eversion carotid endarterectomy versus best medical treatment in symptomatic patients with near total internal carotid occlusion: a prospective nonrandomized trial. Ann Vasc Surg. 2009;24(2):185–189.
93.
RadakDDavidovicLVukobratovV. Carotid artery aneurysms: serbian multicentric study. Ann Vasc Surg. 2007;21(1):23–29.
94.
IlijevskiNGajinPNeskovicVKolarJRadakD. Postendarterectomy common carotid artery pseudoaneurysm. Vascular. 2006;14(3):177–180.
95.
IlijevskiNKrivokapicBSmiljanicB. Carotid endarterectomy in cervical block anesthesia in patients with occluded contralateral internal carotid artery. Srp arh celok lek. 2006;134(3-4):122–128.
96.
RadakDRadevicBSternicN. Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study. Cardiovasc Surg. 2000;8(6):422–428.
