Research On The Relationship Between Serum Inflammatory Markers And Stability Of Carotid Plaques In Patients With Ischemic Cerebrovascular Diseases

Objective:To study the relationship between serum levels of inflammatory markers and stability of carotid plaques in patients with ischemic cerebrovascular diseases and evaluate the ability of each serum marker in identifying vulnerable carotid plaques. To explore a new approach for identifying vulnerable carotid plaques early.Methods:The study included 65 consecutive patients with ischemic cerebrovascular diseases and with carotid plaques confirmed by imaging examinations. Of these patients,17 were diagnosed as transient ischemic attack,44 cerebral infarction and 4 were detected with carotid stenosis incidentally. Patients were excluded if they have any other disease or disease state influencing the expression of serum inflammatory markers.All the patients were examined by digital subtraction cerebral angiography and high resolution magnetic resonance imaging. Patients were classified as stable plaques group (n=21) or unstable plaques group (n=44) according to the characteristic findings of plaques in MRI such as the thickness of fibrous cap, the existence of a large lipid core and intra-plaque hemorrhage. The patients of unstable plaques group were further classified as unrupture plaques group (n=29) and rupture plaques group (n=15) according to the integrity of fibrous cap.Peripheral blood samples of the study patients were collected in tubes containing ethylenediamine tetraacetic acid (EDTA). After centrifugation the serum was siphoned into freezing vials and stored at-80℃. Serum levels of sCD40L, MCP-1, MMP-2, MMP-9, MPO and PAPP-A were determined by enzyme-linked immunosorbent assay (ELISA).Results:Serum levels of sCD40L in patients of unstable plaques group, unrupture plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group, P value being 0.011,0.001 and 0.000 respectively. There was no significant difference in serum levels of sCD40L between unrupture plaques group and rupture plaques group, P value being 0.085.Serum levels of MMP-9 in patients of unstable plaques group, unrupture plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group, P value being 0.045,0.032 and 0.003 respectively. There was no significant difference in serum levels of MMP-9 between unrupture plaques group and rupture plaques group, P value being 0.192.Serum levels of PAPP-A in patients of unstable plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group, P value being 0.008 and 0.000 respectively. Serum levels of PAPP-A in patients of rupture plaques group were significantly enhanced compared to individuals of unrupture plaques group, P value being 0.000. There was no significant difference in serum levels of PAPP-A between unrupture plaques group and stable plaques group, P value being 0.745.Spearman rank correlation indicated that the serum levels of sCD40L, MMP-9 and PAPP-A were positively correlated with the degrees of vulnerability of plaques, r value being 0.556,0.424 and 0.424 respectively, P value being 0.000,0.000 and 0.000 respectively.Logistic regression indicated that the serum levels of sCD40L≥673.22 pg/ml (OR=22.47,95%CI 2.11-239.81), MMP-9≥84.09 ng/ml (OR=10.01,95%CI 1.74-57.78) and PAPP-A≥0.101 ng/ml (OR=14.29,95%CI 2.69-75.90) were all significantly correlated with the vulnerability of carotid plaques, P value being 0.010, 0.010 and 0.002 respectively.There was no significant difference in the serum levels of MCP-1, MMP-2 and MPO between any two groups.Conclusions:There appear to be a relationship between the serum levels of sCD40L, MMP-9 and PAPP-A and the instability of carotid plaques in patients with cerebrovascular diseases and with carotid plaques. High serum levels of the above-mentioned markers may indicate that the plaques were vulnerable or ruptured. Therefore, sCD40L, MMP-9 and PAPP-A can be used as the markers of stability of carotid plaques. It is feasible in some extent to judge whether the plaques are vulnerable or ruptured by the serum levels of the mentioned markers if we take the results from large-sample trials as standards. And it maybe a new approach to identify vulnerable plaques early.