Abstract
Background: In previous proteomics experiments, we have found several proteins to be differentially expressed in human hemorrhagic carotid atherosclerotic plaques, which are considered as unstable, when compared to fibrotic plaques. Circulating concentrations of these proteins may predict cardiovascular outcome in patients with coronary artery disease. Methods and results: Blood samples were drawn in 768 patients who underwent coronary angiography for acute coronary syndrome or stable angina pectoris in a prospective biomarker study in a tertiary center between 2008 and 2011. We selected the 88 patients (cases) with major adverse cardiovascular events (MACE) within one year and 176 controls without MACE, matched on age, sex and number of diseased coronary vessels. MACE was defined as all-cause mortality, acute coronary syndrome, unplanned coronary revascularization and stroke. Thirteen circulating protein biomarkers that were previously found to have altered expression in hemorrhagic plaques were evaluated. Univariable conditional logistic regression analyses showed that baseline plasma neutrophil gelatinase-associated lipocalin (NGAL, p=0.038), osteoglycin (OGN, p=0.011), thrombospondin-2 (p=0.066), pro-B-type natriuretic peptide 1-108 (p=0.088), metalloproteinase inhibitor-1 (p=0.020) and NGAL/matrix metalloproteinase-9 complex (NGAL/MMP9, p=0.070) concentrations were higher in patients with MACE during follow-up. After further adjustment for established cardiovascular risk factors, OGN (OR 1.84 per SD of ln-transformed OGN unit, 95%CI 1.10-3.08, p=0.021) and NGAL/MMP9 (OR 1.76, 95%CI 1.04-2.98, p=0.034) were independently associated with MACE. Conclusions: Circulating OGN and NGAL/MMP9 complex may be promising biomarkers that are expressed in atherosclerotic plaques and that are independently associated with occurrence of MACE after coronary angiography.
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