Oxidized high-density lipoprotein associates with cardiometabolic dysfunction in coronary artery disease and acute coronary syndrome

Background: High-density lipoprotein (HDL) function, rather than its concentration, plays a crucial role in the development of coronary artery disease (CAD). Diminished HDL antioxidant properties, indicated by elevated oxidized HDL (nHDL _ox) and diminished paraoxonase-1 (PON-1) activity, may contribute to vascular dysfunction and inflammation. Data on these associations in CAD patients, including acute coronary syndrome (ACS), remain limited. The aim of this study is to assess the association of oxidized HDL with PON-1 activity, oxidized low-density lipoprotein (LDL), vascular cell adhesion molecule-1 (VCAM-1), IL-6 levels, and nitric oxide (NO) production as markers of vascular health. Methods: We assessed HDL function in three groups: 90 CAD patients, 90 healthy controls, and 90 ACS patients. HDL antioxidant function was measured using a validated biochemical assay to quantify oxidized HDL (nHDL _ox). Plasma PON-1 activity, oxidized LDL, VCAM-1, IL-6, and NO production were also evaluated. Results: ACS patients had nHDL _ox levels 140% higher than healthy controls (p < 0.001). Higher nHDL _ox levels were significantly linked to vascular inflammation, reflected by elevated VCAM-1 levels. Additionally, a reduced PON-1 activity indicates an impaired antioxidant protection in ACS patients. Finally, oxidized LDL levels were elevated, and NO production was reduced, suggesting impaired vascular function. Conclusion: HDL _ox levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS. Clinical trial registration: DRKS00014037.