Abstract

Background: Oxidative stress and inflammatory processes are of major importance in plaque instability. We demonstrated previously that elevated plasma oxidized low-density lipoprotein (ox-LDL) levels are related to plaque instability. In this study, we investigated whether plasma ox-LDL levels were related to the types of intracoronary thrombi (ICT) obtained by percutaneous thrombectomy in 130 patients within 12 hours of onset of acute myocardial infarction (AMI). We also analyzed whether individual types of ICT were related to long-term mortality. Methods: Frozen samples of aspirated ICT from 130 AMI patients were studied. Serial sections were investigated immunohistochemically using antibodies against platelets, red blood cells (RBCs) (glycophorin A) and neutrophils (CD66b and MPO). The ICT were classified into three types: platelet (PL) type (>70% of the ICT surface area consisting of platelets; n=45), RBC type (>70% of the ICT surface area consisting of RBCs; n=31) or mixed type (mixture of platelets and RBCs; n=54). We also measured plasma ox-LDL levels on admission using a specific monoclonal antibody. Results: Plasma ox-LDL levels were significantly higher in the RBC type than in the PL type (RBC, 1.89±1.84; mixed, 1.35±1.21; PL, 1.01±0.94 ng/5 μ g LDL protein; RBC versus PL, P<0.05). Quantitative analysis demonstrated the percentage of MPO-positive neutrophils in the RBC or mixed types were significantly higher than in the PL type (RBC, 35±16%; mixed, 36±18%; PL, 23±17%; RBC versus PL, P<0.05 and mixed versus PL, P<0.005). Over a mean follow-up period of 33.5 months (range 1 day – 87.6 months), there were 17 cases (13%) of cardiac death. Kaplan-Meier survival curves showed that RBC and mixed types had significantly worse mortality than the PL type (P=0.040 by log-rank test). Multivariate analysis demonstrated that RBC and mixed types were independent determinants of long-term mortality (OR, 5.34; 95%CI, 1.083 – 26.37, P=0.039). Conclusions: The present study demonstrates that neutrophil activation and MPO release in mixed or RBC types of thrombi may play a role in generating excessive pro-oxidants. In addition, the presence of thrombi with RBC and mixed types is an independent predictor of long-term mortality.

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