Oxidized Low-Density Lipoprotein Predicts the Development of Renal Dysfunction in Atrial Fibrillation

Abstract

Background/Aim: To investigate the role of oxidative stress (OS) in the development of chronic kidney disease (CKD) in atrial fibrillation (AF). Methods: We compared OS burden, determined at study inclusion as plasma concentrations of oxidized low-density lipoprotein (oxLDL), between stable AF patients (n = 256, mean age: 62.8 ± 9.3 years; 60.9% males) with preserved renal function, defined as an estimated glomerular filtration rate (eGFR) ≥ 60 ml/ min/1.73 m 2 , and a matched control group in sinus rhythm (n = 138, mean age: 61.5 ± 11.2 years; 60.9% males). During the prospective follow-up of AF patients, we investigated the association and prognostic validity of oxLDL for CKD development, diagnosed as a sustained decline in eGFR to <60 ml/min/1.73 m 2 . Results: AF patients had a higher mean oxLDL (76.2 ± 21.7 U/l) compared to sinus rhythm controls (61.6 ± 13.1 U/l; p < 0.001). AF presence independently predicted increased oxLDL levels in the study cohort [β = 14.7; 95% confidence interval (CI), 10.7-18.7; p < 0.001]. Over a median 4-year follow-up, 19.9% of AF patients developed CKD. Adjusting for all clinical covariates, oxLDL (per tertile) was associated with a hazard ratio of 2.17 for CKD occurrence (95% CI, 1.40-3.35; p < 0.001). AF patients in the upper oxLDL tertile ( ≥ 88.7 U/l) had a 3.70-fold (95% CI, 1.55-8.81) higher risk for CKD compared to the lower oxLDL tertile (<67.0 U/l) patients (p < 0.001). oxLDL improved discriminative validity ( cstatistic increment: 0.041, 95% CI, 0.007-0.075, p = 0.017), and increased the net reclassifica- tion and integrated discrimination for CKD risk by 12.4 and 6.0%, respectively (both p < 0.001). Conclusions: oxLDL is increased in AF patients compared to sinus rhythm controls. oxLDL has an independent association and an incremental predictive value that might complement clinical CKD risk assessment in AF patients following further research.

Relationship between lipoproteins, thrombosis, and atrial fibrillation

“…Elevated oxLDL levels (detected by 4E6 mAb) are independently associated with several cardiovascular risk factors including increasing age, male gender, raised body mass index, abdominal obesity, hypertension, raised C-reactive protein, renal dysfunction, hyperuricaemia and smoking 101 . These risk factors are important in AF, which has also been shown to be directly associated with elevated 4E6-measured oxLDL levels [102][103][104][105] .…”

“… 105 These risk factors are important in AF, which has also been shown to be directly associated with elevated 4E6-measured oxLDL levels. 106–109 …”

Reactive Oxygen Species and Their Involvement in Red Blood Cell Damage in Chronic Kidney Disease

“…It has been observed that patients with chronic CKD have increased levels of plasma thiol oxidation even contributing to progressive renal dysfunction [ 112 ]. In turn, OxLDL has recently been reported to predict the development of renal dysfunction [ 113 ]. Another marker of oxidative stress in inflammatory diseases is 3-nitrotyrosine (TyrNO 2 ) associated with the overproduction of NO [ 114 ].…”

Oxidative Stress in Kidney Diseases: The Cause or the Consequence?

“…The accumulation of OxLDL stimulates production of pro-inflammatory cytokines by overlying endothelial cells, and therefore it becomes one of the main mediators of CVD development (Mertens and Holvoet 2001 ), also in patients with kidney diseases (Pandya et al 2015 ). Interestingly, OxLDL has recently been reported to predict the development of renal dysfunction in atrial fibrillation (Polovina et al 2016 ). However, in hemodialyzed patients OxLDL levels did not significantly correlate with the risk major adverse cardiac events (Wagner et al 2017 ), so the applicability of this marker in renal disorders remains to be fully elucidated.…”