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May 14, 2026Diabetes & Metabolism Journal2 citationsOpen Access

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

JGJun-Xu GuJHJuan HuangAZA R Zhang

Key Points

  • This research aims to investigate the prognostic significance of oxidized lipoproteins for major adverse cardiovascular events in patients with type 2 diabetes and coronary heart disease.
  • Multicenter cohort study involving 3,733 patients with angiographically confirmed T2DM-CHD
  • Follow-up period of 5 years, measuring circulating oxidized lipoproteins and assessing associations with coronary severity and MACEs
  • Statistical analyses using Cox regression, Kaplan-Meier, and restricted cubic spline models to evaluate risk associations.
  • Patients with MACEs had higher levels of ox-HDL-C, ox-LDL-C, and ox-Lp(a), which correlated with greater coronary lesion burden and impaired β-cell function.
  • Risk of MACEs increased above specific thresholds for oxidized lipoproteins (19.88 ng/mL for ox-HDL-C, 25.71 ng/mL for ox-LDL-C, and 19.96 μmol/L for ox-Lp(a)).
  • Individuals in the highest quartile of oxidized lipoproteins showed significantly elevated MACEs risk compared to those in the lowest quartile, with adjusted HRs for ox-HDL-C at 1.872, ox-LDL-C at 2.239, and ox-Lp(a) at 1.917, all with p<0.001.

Abstract

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.

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Cite This Study

Gu et al. (2026) studied this question.

synapsesocial.com/papers/6a0567d2a550a87e60a1ffc6https://doi.org/10.4093/dmj.2025.1029
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