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Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis
Sandra Wagner1, Mugurel Apetrii2,3, Ziad A Massy1,2
1a Inserm U1018, Université Paris-Saclay, UVSQ, Université Paris-Sud , Villejuif , France.
Insights
Oxidized low-density lipoprotein (oxLDL) was not associated with major adverse cardiac events (MACE) or mortality in hemodialysis patients. Statin treatment did not improve outcomes by reducing oxLDL levels in this population.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Biochemistry
Background:
- Statins benefit the general population but show limited efficacy in hemodialysis (HD) patients, suggesting different cardiovascular disease (CVD) pathophysiology.
- Oxidative stress, potentially involving oxidized low-density lipoprotein (oxLDL), may play a role in CVD in HD patients.
Purpose of the Study:
- To investigate the association of baseline oxLDL with major adverse cardiac events (MACE) and all-cause mortality in HD and non-HD patients.
- To determine if statin-induced reduction in oxLDL improves cardiovascular outcomes in HD patients.
Main Methods:
- Analysis of baseline oxLDL levels and their association with MACE and mortality using Cox proportional hazard models in the AURORA (HD) and LURIC (non-HD) studies.
- Assessment of oxLDL changes during statin treatment (rosuvastatin) and their correlation with outcomes.
Main Results:
- Lower baseline oxLDL was associated with higher MACE risk in AURORA, but this association disappeared after adjusting for apolipoprotein B.
- Baseline oxLDL was not related to mortality in the LURIC study.
- Statin treatment reduced oxLDL by 30.9% at 3 months, but this reduction was not significantly linked to improved MACE or mortality rates.
Conclusions:
- No significant association was found between oxLDL and MACE after adjusting for apolipoprotein B, possibly due to assay properties.
- Rosuvastatin did not demonstrate improved cardiovascular outcomes through oxLDL reduction in HD patients.
- Further research is needed to explore oxidative stress modification strategies for CVD risk in HD patients.
Abstract:
Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 ± 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 ± 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.
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