Gender-specific correlation between plasma myeloperoxidase levels and serum high-density lipoprotein-associated paraoxonase-1 levels in patients with stable and unstable coronary artery disease

Abstract

ObjectiveLow high-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease (CAD) and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Recently, myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. This study investigated the relationship between plasma MPO and serum PON-1 levels in patients with stable (SAP) and unstable angina pectoris (UAP). MethodsPlasma MPO levels and serum PON-1 concentration/activity were measured in patients with SAP (n = 226), UAP (n = 151) and in control subjects (n = 99). ResultsPlasma MPO levels in UAP patients were significantly higher than those in SAP patients or in control subjects (UAP, 21.6[16.7–44.6]; SAP, 19.3[15.7–29.1]; control, 15.9[14.7–18.7] ng/mL; P < 0.0001). Serum PON-1 concentrations in UAP and SAP patients were significantly lower than those in control subjects (UAP, 55.6[45.9–69.7]; SAP, 55.0[46.9–64.9]; control, 62.5[51.1–78.8] μg/mL; P = 0.0002). Plasma MPO levels showed a weak inverse correlation with serum PON-1 concentrations in all subjects (R = −0.163, P < 0.0005). Moreover, in women, plasma MPO levels showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity in SAP (concentration: R = −0.537, P < 0.0001; arylesterase-activity: R = −0.469, P < 0.001) and UAP (concentration: R = −0.340, P < 0.05; arylesterase-activity: R = −0.350, P < 0.05) patients, but not in men. ConclusionThis study demonstrates that plasma MPO levels have a significant inverse correlation with PON-1 levels, especially in women, in SAP and UAP patients, and suggests that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression of coronary plaque instability.