Therapeutic Lifestyle Changes Improve HDL Function by Inhibiting Myeloperoxidase-Mediated Oxidation in Patients With Metabolic Syndrome

OBJECTIVE: Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are associated with metabolic syndrome (MetS) and increased cardiovascular disease risk. Therapeutic lifestyle changes (TLCs), such as a Mediterranean diet and exercise, decrease this risk. However, the link among TLCs, HDL, and MPO-mediated oxidative stress remains unclear. RESEARCH DESIGN AND METHODS: In this study, we characterized changes in cholesterol efflux capacity (CEC), a metric of HDL function; MPO-mediated oxidation; and the HDL proteomic profile in 25 patients with MetS who underwent 12 weeks of TLCs. RESULTS: After 12 weeks, before significant changes to HDL levels, most MetS components improved as a result of the TLCs. CEC was significantly increased, and HDL MPO oxidation products, 3-chlorotyrosine and 3-nitrotyrosine, were decreased with TLCs. The changes in CEC were inversely related to the unit changes in 3-chlorotyrosine after we controlled for changes in the other MetS components. TLCs did not remodel the HDL proteome. CONCLUSIONS: In summary, TLCs improved HDL function by inhibiting MPO-mediated oxidative stress even before appreciable changes in HDL levels.