Oxidized Lipoproteins as Independent Predictors of Major Adverse Cardiovascular Events in Type 2 Diabetes Mellitus with Coronary Heart Disease: A Multicenter Prospective Cohort Study

Background: Oxidized lipoproteins contribute to atherosclerosis and metabolic dysfunction; however, their prognostic significance for major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and coexisting coronary heart disease (CHD) remains unclear. Methods: This multicenter cohort included 3,733 patients with angiographically confirmed T2DM-CHD, followed for 5 years. Baseline circulating oxidized high-density lipoprotein cholesterol (ox-HDL-C), oxidized low-density lipoprotein cholesterol (ox- LDL-C), and oxidized lipoprotein(a) (ox-Lp(a)) were measured, and associations with coronary severity, β-cell function, and MACEs were analyzed using Cox regression, Kaplan-Meier, and restricted cubic spline models. Results: Patients with MACEs had higher baseline ox-HDL-C, ox-LDL-C, and ox-Lp(a), correlating with greater coronary lesion burden and impaired β-cell function. Restricted cubic spline analyses revealed nonlinear, dose-dependent associations, with MACEs risk increasing above thresholds of 19.88 ng/mL (ox-HDL-C), 25.71 ng/mL (ox-LDL-C), and 19.96 μmol/L (ox-Lp(a)), with sexspecific differences observed. In Cox proportional hazards models, individuals in the highest quartile of oxidized lipoproteins had significantly elevated 5-year MACEs risk compared to those in the lowest quartile, and these associations remained robust after adjusting for confounders (ox-HDL-C: adjust hazard ratio [HR], 1.872; 95% confidence interval [CI], 1.408 to 2.489; P<0.001; ox- LDL-C: adjust HR, 2.239; 95% CI, 1.686 to 2.974; P<0.001; ox-Lp(a): adjust HR, 1.917; 95% CI, 1.442 to 2.549; P<0.001). Conclusion: Oxidized lipoproteins are independent predictors of MACEs in patients with T2DM-CHD and reflect vascular and metabolic dysfunction. Incorporating oxidized lipoprotein profiling into clinical risk assessment may improve early identification of high-risk individuals and guide preventive strategies.