Mediators of Inflammation / 2015 / Article / Tab 2

Review Article

Markers of Inflammation Associated with Plaque Progression and Instability in Patients with Carotid Atherosclerosis

Table 2

Summary of the main studies concerned with the relationship between carotid artery atherosclerosis and its relationship with circulating inflammatory biomarkers.

AuthorPatientsMarkersResults

Puz et al. [24]9526 asymptomatic carotid artery stenosis  patients
39 symptomatic carotid artery stenosis  patients
30 healthy controls
Leucocyte count, ESR, CRP, fibrinogen, TNFα, IL1β, IL-6 and IL10, and anti-cytomegalovirus IgG antibody titreIL-6, fibrinogen, ESR, and CRP are higher in patients than in the control group. TNFα, IL-6, fibrinogen, number of leukocytes, monocytes, and CRP are higher in symptomatic patients than in asymptomatic patients

Debing et al. [25]360180 asymptomatic carotid artery stenosis patients  
180 healthy controls
hs-CRP, sVCAM-1, and IL-6hs-CRP, sVCAM-1, and IL-6 are higher in patients with stenosis than in healthy controls and correlate with the degree of stenosis

Halvorsen et al. [26]53413205 asymptomatic carotid artery stenosis  patients
2136 healthy controls
White blood cell count, fibrinogen, and CRPWhite blood cells and fibrinogen were associated with the presence of plaque

Chapman et al. [27]1111Randomly selected, population-basedIL-6, hs-CRP, fibrinogen, monocyte count, and white blood cellsOnly monocyte counts were associated with carotid artery plaque upon multivariate analysis

Abbas et al. [34]181159 high grade carotid artery stenosis  patients
22 healthy controls
S100A8, S100A9, and S100A12S100A12 levels were higher in patients with carotid atherosclerosis and highest in symptomatic patients. S100A8 and S100A9 were higher in symptomatic patients

Andersson et al. [35]1016Population-based survey. All individuals were 70 years of ageApolipoprotein B/A1 ratio, OxLDL, TNFα, HOMA insulin resistance, leucocyte count, BCD-LDL, L-selectinInflammatory markers associated with plaque size

Shindo et al. [38]5858 asymptomatic carotid artery stenosis patients undergoing surgical or endovascular interventionIL-6, IL1β, IL10, TNFα, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3PTX3 associated with histologic features of plaque vulnerability

Willems et al. [39]39175 asymptomatic carotid artery stenosis  patients
316 symptomatic carotid artery stenosis patients
s = serum ST2No association with features of plaque instability

Sugioka et al. [40]102102 asymptomatic carotid artery stenosis patients with stable coronary artery diseaseNeopterinNeopterin associated with complex plaque morphology

Pelisek et al. [41]10137 histologically stable asymptomatic lesions 
64 histologically unstable lesions
Serum levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2, TNFα, IL-1β, IL-6, IL-8, IL-10, and IL-12MMP-1, MMP-7, TIMP-1, TNFα, and IL-8 were higher in the sera of patients bearing histological features of plaque instability

Koutouzis et al. [45]11957 asymptomatic patients  
62 symptomatic patients
IL-6, TNFα, IL-1β, SAA, and hs-CRPIL-6 was found higher in symptomatic patients

Garcia et al. [46]6236 symptomatic  patients
26 asymptomatic patients
hs-CRPhs-CRP was higher in symptomatic patients

Handberg et al. [47]6216 symptomatic patients <2 months 
15 symptomatic patients, 2–6 months 
31 asymptomatic patients
CD36Soluble CD36 was higher in recently symptomatic patients, that is, symptoms <2 months

Edsfeldt et al. [49]16292 symptomatic carotid artery stenosis  patients
70 asymptomatic high grade stenosis patients
suPARsuPAR was higher in symptomatic patients and correlated with higher histological signs of inflammation

Olson et al. [50]255255 symptomatic carotid artery stenosis patientssuPAR(I–III), suPAR(II-III), and uPAR(I)suPAR(I–III) and suPAR(II-III) were higher in TIAs and strokes than in amaurosis fugax

Basta et al. [51]2919 symptomatic carotid artery stenosis  patients
10 asymptomatic carotid artery stenosis patients
sRAGEsRAGE was higher in symptomatic patients

Abbas et al. [52]205182 asymptomatic carotid artery stenosis patients  
23 healthy controls
MMP-7 MMP-7 was higher in patients with carotid artery stenosis than in healthy controls, with highest values in symptomatic patients

Duivenvoorden et al. [55]130130 patients with stable coronary artery diseaseMyeloperoxidase, hs-CRP, IL-6, soluble P-selectin, soluble E-selectin, sICAM1, sVCAM-1, MMP-3, and MMP-9Only myeloperoxidase correlated with baseline carotid artery FDG TBR in its most diseased segment

Mani et al. [56]130130 patients with stable coronary artery diseaseIL-6, LpPLA2, apolipoprotein A-I, and hs-CRPIL-6 correlated with baseline carotid artery FDG TBR in its most diseased segment

Rudd et al. [57]4141 suffering from atherosclerosis in multiple vascular districtsMMP-3, MMP-9, hs-CRP, fibrinogen, IL18, adiponectin, and PAI1Levels of MMP-3 correlated with carotid artery FDG TBR, while a negative correlation was established between carotid TBR and PAI1

Grufman et al. [58]160160 patients undergoing carotid endarterectomyhs-CRPBlood levels of hs-CRP did not correlate with inflammatory activity within the plaque

Norata et al. [65]156156 healthy volunteersLDL-RF, TGRL, and sdLDLLDL-RF, TGRL, and sdLDL correlated with carotid IMT in healthy volunteers

Holm et al. [77]26128 asymptomatic carotid artery stenosis  patients
31 symptomatic carotid artery stenosis  patients
202 acute stroke patients, 4.4-year follow-up
FABP4FABP4 was higher in atherosclerotic patients and associated with cardiovascular mortality in the acute stroke cohort

Mayer et al. [87]853853 symptomatic carotid artery stenosis patientsNeutrophils, eosinophils, basophils, monocytes, lymphocytes, and total leukocyte countNeutrophils predicted cardiovascular mortality during 6-year follow-up

Nasr et al. [88]6060 symptomatic carotid artery stenosis patientsNeutrophil, lymphocytes, and monocytes countsNeutrophils predicted the occurrence of microembolic events on transcranial Doppler ultrasound

Jurk et al. [89]10348 asymptomatic carotid stenosis patients 
25 patients with previous stroke 
30 healthy controls
Surface CD11b, P-selectin, and TSP-1 on macrophages. Platelet-monocytes aggregatesTSP-1 and P-selectin were higher on the surface of monocytes from symptomatic patients

Ritter et al. [91]4630 asymptomatic carotid stenosis  patients
16 recently symptomatic carotid stenosis patients
P-selectin and thrombospondin expressions on platelets. Soluble P-selectinHigher soluble P-selectin was found in patients with microembolic signals on transcranial Doppler

Sternberg et al. [92]7240 patients undergoing carotid endarterectomy (both symptomatic and asymptomatic)  
32 healthy controls
MMP-9 and PPAR-γ expression levels in circulating monocytes. Several monocytes activation markersMonocytes from patients suffering from carotid atherosclerosis displayed higher levels of activation, MMP-9, and PPAR-γ than in healthy controls

Martin-Ventura et al. [93]27570 patients undergoing carotid endarterectomy 
205 healthy controls
CD74 expression in PBMCCD74 expression was higher in PBMC of patients suffering from carotid atherosclerosis. In healthy controls it correlated with IMT

Mantani et al. [94]700700 subjects from the cardiovascular cohort from the Malmo studyCD19+CD40+ and CD19+CD86+ B cells countCD19+CD86+ B cells were shown to correlate with the degree of carotid artery stenosis and the risk of stroke. CD19+CD40+ B cells were shown to predict a low risk of stroke

Baragetti et al. [97]768768 patients from the PLIC studyLTLLTL was inversely correlated with IMT and the occurrence of cardiovascular events

Schulze Horn et al. [102]30923092 subjects over 55 years of age from the INVADE studyhs-CRPhs-CRP was shown to correlate with IMT

Orbe et al. [103]400400 healthy subjectsMMP-1, MMP-9, and MMP-10, fibrinogen, IL-6, von Willebrand factor, and hs-CRPMMP-10 was associated with IMT

Olson et al. [104]912912 participants in the MESA studyCD4+CD45RA+ (naive) and CD4+CD45RO+ (memory) T cellsIMT negatively correlated with the percentage of circulating naïve T cells

Ammirati et al. [105]183183 free living subjectsCD3+CD4+CD45RA−CD45RO+CCR7− T effector memory cellsT effector memory cells were strongly associated with IMT

Rogacev et al. [106]622622 healthy volunteersCD14++CD16−, CD14++CD16+, and CD14+CD16+ cells monocytesCD16+ monocytes were associated with IMT

Qian et al. [111]4040 patients undergoing carotid endarterectomySoluble CD146Soluble CD146 correlated with histologically determined plaque neovascularization

Pelisek et al. [112]5628 stable lesions determined by histology 
28 unstable lesions determined by histology
VEGFVEGF was higher in patients bearing plaques with histological features of instability and correlated with the degree of neovascularization

Jaipersad et al. [113]12040 severe (>50%) asymptomatic carotid stenosis and stable angina patients  
40 patients with stable angina and stenosis of <50% 
40 hypercholesterolaemic controls
CD14++ CD16−CCR2 +, CD14+CD16++ CCR2−, and CD14++ CD16+CCR2+ monocytes and their surface expression of TLR4, IL-6 receptor, and Tie2TLR4 and Tie2 were enriched in all monocytes subsets of patients suffering from carotid stenosis. CD14++CD16−CCR2+ monocytes correlated with carotid stenosis and IMT and were associated with severe plaque neovascularization

ESR: erythrocytes sedimentation rate; CRP: C-reactive protein; TNFα: tumour necrosis factor α; IL: interleukin; sVCAM: soluble vascular cell adhesion molecule; OxLDL: oxidized lipoproteins; HOMA: homeostasis model assessment; BCD-LDL: baseline conjugated dienes of low-density lipoprotein; PTX3: pentraxin-3; MMP: matrix metalloproteinase; TIMP: tissue inhibitor of matrix proteinases; SAA: serum amyloid A; suPAR: soluble urokinase plasminogen activator receptor; sRAGE: soluble receptor of advanced glycation end products; sICAM: soluble intercellular adhesion molecule; LpPLA2: lipoprotein-associated phospholipase A2; PAI1: plasminogen activator inhibitor; LDL-RF: LDL relative floatation; TGRL: triglyceride-rich lipoproteins; sdLDL: small dense LDL; FABP4: fatty acid binding protein 4; TSP-1: thrombospondin 1; PPARγ: peroxisome proliferator-activated receptor γ; PBMC: peripheral blood mononuclear cells; LTL: leukocyte telomere length; VEGF: vascular endothelial growth factor; TLR4: toll-like receptor 4.

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