Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis.
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.
a Inserm U1018, Université Paris-Saclay, UVSQ, Université Paris-Sud , Villejuif , France.
Sandra
S
Wagner
b Service de Néphrologie , Hôpital Ambroise Paré APHP , Boulogne-Billancourt , France.|c Department of Nephrology , University of Medicine and Pharmacy "Gr. T. Popa" , Iasi , Romania.
Mugurel
M
Apetrii
a Inserm U1018, Université Paris-Saclay, UVSQ, Université Paris-Sud , Villejuif , France.|b Service de Néphrologie , Hôpital Ambroise Paré APHP , Boulogne-Billancourt , France.
Ziad A
ZA
Massy
d Institute of Nutrition , Friedrich Schiller University Jena , Jena , Germany.|e Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim , Heidelberg University , Mannheim , Germany.
Marcus E
ME
Kleber
e Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim , Heidelberg University , Mannheim , Germany.
Graciela E
GE
Delgado
f Clinical Institute of Medical and Chemical Laboratory Diagnostics , Medical University Graz , Graz , Austria.
Hubert
H
Scharnagel
e Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim , Heidelberg University , Mannheim , Germany.|f Clinical Institute of Medical and Chemical Laboratory Diagnostics , Medical University Graz , Graz , Austria.|g Synlab Academy , Synlab Holding Deutschland GmbH , Mannheim , Germany.
Winfried
W
März
a Inserm U1018, Université Paris-Saclay, UVSQ, Université Paris-Sud , Villejuif , France.
Marie
M
Metzger
h Inserm, Centre d'Investigations Cliniques - Plurithématique 14-33, and Inserm U1116, CHU de Nancy, and Université de Lorraine, France and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy , France.|i Association Lorraine de Traitement de l'Insuffisance Rénale (ALTIR) , Vandoeuvre-lès-Nancy , France.
Patrick
P
Rossignol
j British Heart Foundation Glasgow Cardiovascular Research Centre , Glasgow , UK.
Alan
A
Jardine
k Rikshospitalet , Oslo , Norway.
Hallvard
H
Holdaas
l University Hospital , Uppsala , Sweden.
Bengt
B
Fellström
m University Hospital , Erlangen-Nürnberg , Erlangen , Germany.
Roland
R
Schmieder
a Inserm U1018, Université Paris-Saclay, UVSQ, Université Paris-Sud , Villejuif , France.
Bénédicte
B
Stengel
h Inserm, Centre d'Investigations Cliniques - Plurithématique 14-33, and Inserm U1116, CHU de Nancy, and Université de Lorraine, France and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy , France.
Faiez
F
Zannad
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D003131:Combined Modality Therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000628:therapy*; D008077:Lipoproteins, LDL / Q000097:blood*; D008875:Middle Aged; D018384:Oxidative Stress; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000068718:Rosuvastatin Calcium
Oxidized LDL; cardiovascular risks; hemodialyzed patients; mortality; statin