Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease

Abstract

BackgroundA residual risk of cardiovascular disease tends to persist despite standard prevention therapy with statins. This may stem partly from increased oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be further reduced beyond statin therapy in high-risk diabetes patients remains unclear. We aimed to clarify the clinical factors associated with oxidized LDL levels in statin-treated high-risk diabetes patients.MethodsThis cross-sectional observational study included 210 diabetes patients with coronary artery diseases (CAD) who were treated with statins. We determined serum malondialdehyde-modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb) A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the factors influencing the MDA-LDL level.ResultsIn univariate analysis, the MDA-LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p < 0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not with age, body mass index, waist circumference, blood pressure, or HbA1c levels. Even after adjusting for the LDL cholesterol level, the correlations between the MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still significant. Among these significant factors, multivariate analysis revealed that the MDA-LDL level was independently associated with the LDL cholesterol, TG, and HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also significantly associated with the CRP level (p = 0.014) and the remnant lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol level. The number of metabolic syndrome (MS) components was significantly associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the use of metformin and α-glucosidase inhibitors was inversely associated with high MDA-LDL levels (p = 0.033 and 0.018, respectively).ConclusionIn statin-treated diabetes patients with CAD, the MDA-LDL level was significantly correlated with TG and HDL cholesterol levels. Adiponectin level was also significantly associated with the MDA-LDL level, but not independent of the above-mentioned factors. The management of dyslipidemic MS components, including the use of metformin or α-glucosidase inhibitors, may be important for reducing the oxidized LDL levels beyond statin therapy in high-risk diabetes patients.

Oxidized low density lipoprotein and total antioxidant capacity in type-2 diabetic and impaired glucose tolerance Saudi men

“…Thus, they suggest that in addition to statin therapy, the management of dyslipidemic MS components is important for reducing the oxidization of LDL and, ultimately, the risk of cardiovascular events in high-risk DM patients [17]. …”

Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk

“…Adiponectin levels were also significantly correlated with MDA-LDL levels, although not independently of TG and HDL cholesterol [59]. The serum MDA-LDL level was significantly associated with serum remnant lipoprotein cholesterol levels [59]. Activation of lectin-like oxidized LDL receptor 1 by remnant lipoprotein particles induced NADPH oxidase-dependent production of superoxide in endothelial cells [60], which may explain the significant association between LDL oxidation and remnant lipoproteins rich in TG.…”

“…Our recent clinical study suggested that in high-risk DM patients treated with statins, the circulating levels of malondialdehyde-modified LDL (MDA-LDL), a surrogate marker of oxidized LDL, were significantly correlated with the TG and HDL cholesterol levels [59]. Adiponectin levels were also significantly correlated with MDA-LDL levels, although not independently of TG and HDL cholesterol [59].…”

Decreased oxidized low-density lipoprotein is associated with improved trunk flexibility in Japanese community-dwelling women

“…Oxidative stress plays an important role in muscle aging and damage to proteins and DNA. 21,22 Recent data have suggested that circulating MDA-LDL level can also be considered a marker of oxidative stress, 23 and increased MDA content induces DNA damage in human skeletal muscles. 24 There are studies that have demonstrated that there is an age-dependent increase in MDA content in skeletal muscle.…”