Clinical Significance of Myeloperoxidase, Neopterin, and High Sensitivity C-Reactive Protein as Independent Predictors of Cardiovascular Events

Background: We previously demonstrated that inflammatory biomarkers such as myeloperoxidase (MPO), a member of the heme peroxidase superfamily, and neopterin (produced by activated macrophages after interferon-γ stimulation by T-lymphocytes) are important in the pathogenesis of coronary plaque instability. Additional evidence supports high sensitivity C-reactive protein (hs-CRP) as an independent predictor of increased coronary risk. We assessed the prognostic significance of plasma MPO and neopterin levels, and serum hs-CRP levels in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). Methods: Plasma MPO, neopterin, and serum hs-CRP levels were measured in 219 SAP patients and 144 UAP patients at admission. Cardiovascular (CV) events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Over a mean follow-up of 27±14 months, 56 SAP patients (26%) had CV events. When SAP patients were stratified based on the median neopterin level (15.0 nmol/L), Kaplan-Meier analysis showed that the high-neopterin group (>15.0 nmol/L) had significantly worse outcomes (P=0.015) than the low-neopterin group. Multivariate analysis showed that elevated neopterin was the only independent factor associated with CV events (OR, 2.19; 95% CI, 1.18-4.09; P=0.014). In contrast, over a mean follow-up of 30±24 months, 33 UAP patients (23%) had CV events. When UAP patients were divided based on the median MPO level (16.0 ng/mL), Kaplan-Meier analysis showed that the high-MPO group (>16.0 ng/mL) had significantly worse outcomes (P=0.012) than the low-MPO group. Multivariate analysis showed that elevated MPO was the only independent factor associated with CV events (OR, 2.58; 95% CI, 1.07-6.23; P=0.035). With regard to hs-CRP levels, there were no significant differences in CV events between the two groups according to the median hs-CRP in both SAP and UAP patients. Conclusions: The clinical significance of elevated MPO and neopterin levels as independent predictors of CV events differs depending on the clinical condition of SAP and UAP patients, because of different production mechanisms of these biomarkers.