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Page 6 of 10 Mueller et al. Vessel Plus 2018;2:13 I http://dx.doi.org/10.20517/2574-1209.2018.19

Table 4. Inflammatory plasmatic biomarkers according to presence or absence of MES
MES+ MES- P value
(n = 19), pg/mL (n = 88), pg/mL
MMP-9 257,003 230,582 0.9938
MMP-8 11,885 9698 0.4884
MMP-3 13,022 24,087 0.001
MMP-2 319,239 344,595 0.06
TNF-α 5.8 5.3 0.6712
ICAM-1 304,084 272,250 0.03
VCAM-1 1,250,217 963,976 0.2967
P-selectin 69,370 100,415 0.009
E-selectin 35,766 39,562 0.22
RANTES 40,975 47,131 0.3653
MCP-1 265 270 0.6836
MPO 83 85 0.7081
IL-6 1.3500 1.3500 0.9022
IL-1 1968 1794 0.2006
lp-PLA2 124 139 0.7652
TBR 2.3 1.8 0.01
MMP: matrix-metalloproteases; TNF: tumor necrosis factor; ICAM: intercellular adhesion molecule; VCAM: vascular cell adhesion
molecule; MCP: monocyte chemoattractant protein; MPO: myeloperoxidase; IL: interleukin; lp-PLA2: lipoprotein-associated
phospholipase; TBR: target to background ratio; MES: microembolic signal

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Table 5. Sensitivity and specificity of biomarkers to predict high TBR values of FDG or presence of MES
Sensitivity (%) Specificity (%) AUC Criterion P value
RANTES 82 42 0.614 > 27,835 pg/mL 0.03
ICAM-1 90 42 0.615 > 239,642 pg/mL 0.015
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AUC: area under the curve; ICAM: intercellular adhesion molecule; TBR: target to background ratio; MES: microembolic signal; FDG:
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Fluorodoeoxyglucose
DISCUSSION
The clinical role of plasmatic biomarkers in the setting of carotid atherosclerosis has been extensively studied
in these recent years [17-19] . This not only for the assessment of the embolic risk but also for the choice of the
best type of carotid intervention [20-22] .

The present study has examined the relationship between plasmatic mediators of inflammation, FDG
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uptake in carotid plaques and the presence of MES. We found a significant correlation between higher FDG
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uptake and the plasmatic levels chemokine RANTES [Table 3 and Figure 1]. Furthermore in MES+ patients
higher levels of ICAM-1 were present.

In the dal-PLAQUE study, baseline FDG uptake positively correlated with blood MPO and IL-6 [23,24] .
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Interestingly, hs-CRP, P-selectin, E-selectin, ICAM-1, MMP-3 and MMP-9 did not correlate with TBR
values [23,24] . In an earlier report by Rudd et al. , FDG uptake was significantly associated with serum MMP-
[9] 18
9 levels. We did not find a correlation of PET-CT to MMP-9 in our study. One possible explanation is that
MMP-9 may be influenced by the burden of ischemic brain lesions and does not only reflect inflammation
within the carotid plaque. Supporting this hypothesis, we found a higher level of MMP-9 in stroke in contrast
to TIA patients with a trend towards significance [Table 2].

Chemokines coordinate communication between circulating inflammatory cells and endothelium [25,26] . We
found that circulating RANTES correlated positively to FDG uptake in the carotid plaque, but there was no
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significant difference between symptomatic and asymptomatic patients. These findings are inline to those of
Zaremba et al. who found no differences in RANTES levels between the sera of stroke patients and those of
[27]