Relationship Between Multiple Plasma Biomarkers and Vulnerable Plaque Determined by Virtual Histology Intravascular Ultrasound

Abstract

Background:The relationship between plasma biomarkers and vulnerable plaque is not well understood. Methods and Results:The 188 patients who underwent 3-vessel virtual histology (VH) intravascular ultrasound (IVUS) with peripheral blood sampling were enrolled. Plasma levels of matrix metalloproteinase 2 and 9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1, adiponectin, and macrophage migration inhibitory factor were measured. VH-IVUS-derived thin cap fibroatheroma (VH-TCFA) was defined as a necrotic core >10% of plaque area in the presence of >40% plaque burden. There were 38 patients with ruptured plaque and 150 patients without (107 patients with VH-TCFA, 43 patients without VH-TCFA) in culprit/target lesions. Among the biomarkers, only the MMP-9 level was significantly higher in patients with ruptured plaque (P=0.002). In the subgroup without ruptured plaque, significant differences in the levels of several biomarkers were not observed between patients with and without VH-TCFA. In both culprit/target and nonculprit/non-target vessels, the MMP-9 level showed a weak correlation with the total number of ruptured plaques (r=0.231, P=0.002).Conclusions: Among the biomarkers tested in this study, the MMP-9 level was significantly higher in patients with ruptured plaque. However, measurement of several biomarkers, including MMP-9, was incapable of predicting the presence of VH-TCFA. (Circ J 2010; 74: 332 - 336)

Virtual Histology Evaluation of Atherosclerosis Regression During Atorvastatin and Ezetimibe Administration - HEAVEN Study -

“…The reason why we saw an increase in hsCRP in both groups is unclear, but it may be related to the large number of smokers in both groups (68.3% in A and 61.7% in S group) because a higher level of hsCRP is described in smokers with CAD. 32 The level of hsCRP did not correlate with plaque volume or plaque composition, and a similar finding was reported by Park et al 33 All other markers decreased during the present study, but differences between groups and differences between baseline and follow-up were not significant.…”

Matrix Metalloproteinase-9 for the Earliest Stage Acute Coronary Syndrome - Comparison With High-Sensitivity Troponin T -

“…[15][16][17][18] Previous studies, which evaluated plaque rupture using intravascular ultrasound and virtual histology intravascular ultrasound, indicated that MMP-9 levels were significantly higher in ACS patients with plaque rupture than those without. 19, 20 Thus, previous studies have provided evidence that MMP-9 reflects atherosclerotic plaque rupture or vulnerability, but the diagnostic value or time-dependent changes of MMP-9 at the earliest stage of ACS have not been compared with other biomarkers. Depending on the molecular mechanisms of the pathogenesis, it is reasonable to hypothesize that elevation of MMP-9 may precede that of biomarkers for cardiac damage, including high-sensitivity troponin T (hs-TnT).…”

Biomarkers and Coronary Atherosclerotic Burden and Activity as Assessed by Coronary Angiography and Intra-Coronary Imaging Modalities

“…Taken together, these data suggest the intriguing possibility that the association between CRP and risk of cardiovascular events is mediated by unstable plaque phenotype, raising the possibility that CRP is not only a marker of vascular inflammation but also of plaque disruption. However, Park et al (Park et al, 2010) recently enrolled 188 patients who underwent 3-vessel VH-IVUS with peripheral blood sampling, including CRP levels measurements. VH-TCFA was defined as a necrotic core >10% of plaque area in the presence of >40% plaque burden.…”

“…However, it is worth mentioning that when lesions are analyzed post-rupture, after the necrotic core may have embolized, they most often appear "dark-green" and will be classified as fibrotic plaque rather than necrotic core in VH-IVUS analysis, and have a reduced calculated relative size of the necrotic core. Therefore, when the relationships between each plaque characteristic and plasma biomarker levels, including CRP, were evaluated in the study performed by Park et al (Park et al, 2010), ruptured plaques were excluded to avoid the possibility of incorrect VH-IVUS interpretation and this may partially explain the different results between studies. Takano et al (Takano et al, 2005) have evaluated, using coronary angioscopy, changes of ruptured plaques in non culprit lesions in living patients and ability of CRP to predict disease activity of the plaque ruptures, also shown in other previous studies (Ishibashi et al, 2002).…”

“…Compared with the control group, the plasma levels of CRP, MMP-2, MMP-9 and PAPP-A were markedly elevated (p=0.033, 0.0001, 0.0001, 0.027, respectively). Park et al (Park et al, 2010) recently enrolled 188 patients who underwent 3-vessel VH-IVUS with peripheral blood sampling, including plasma levels of MMP-2,-9, tissue inhibitor of metalloproteinase-1, adiponectin, macrophage migration inhibitory factor, along with CRP levels measurements. Among the biomarkers, only the MMP-9 level was significantly higher in patients with ruptured plaque (p=0.002).…”