Ciencias Médicas y de la Salud
Oxidized LDL is associated with Metabolic Syndrome independently of obesity and insulin resistance
Yamilee Hurtado-Roca(1,2),*, Martin Laclaustra(1,2)
(1) Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
(2) CIBERESP. Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain.
*email@example.com, Tel: (+34) 914531200, Fax: (+34) 91 4531245
BACKGROUND AND AIMS: Oxidative stress is defined as an imbalance between oxidants and antioxidants; this process is suspected to be involved in the pathophysiology of several chronic diseases. The biochemical consequences include mainly damage to proteins, nucleic acid bases, and lipids, some of which can be used as oxidative stress biomarkers like oxidized-low density lipoproteins (ox-LDL). Metabolic syndrome (MS) is associated with oxidative stress. Several studies have examined the involvement of ox-LDL in the development of metabolic syndrome. However, no study has examined the relationship between oxidative stress and MS and its components analyzing either the potentially suspected mediator role of oxidative stress or its effects independent of obesity and insulin resistance.
METHODS: We used baseline data from 3987 non-diabetic subjects in the Progression and Early detection of subclinical Atherosclerosis (PESA) Study. We estimate adjusted odds ratios (ORs) across quartiles of ox-LDL. Using mediation analysis, we analyzed to what extent ox-LDL mediates the effect of waist circumference on the MS and to what extent insulin resistance (HOMA-IR) mediates ox-LDL effect on the MS. Confidence intervals (95% CIs) were calculated for all estimations. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed using R statistical software.
RESULTS: The prevalence of MS criteria and MS increased across ox-LDL quartiles. These associations were independent of insulin resistance and anthropometric measurements. Odds ratio for the metabolic syndrome was 2.57 (1.66, 4.04) in the 4th quartile of ox-LDL versus the 1st quartile independently of HOMA-IR, BMI, and waist circumference. The effect of waist circumference on metabolic syndrome-related parameters that is mediated by ox-LDL reflects higher ox-LDL only mediates 13.9 % of the influence of waist circumference on triglycerides and between 1 and 3% of the influence on HDL-cholesterol, blood pressure, and insulin concentration.
CONCLUSIONS: Higher concentrations of ox-LDL were associated with MS and its components. Moreover, our study suggests that lipid peroxidation products no belong to the same way that obesity to produce MS, those have an independent effect to MS. We propose that increased ox-LDL is an important underlying cause of metabolic syndrome; hence this oxidative stress biomarker could be use, in all population independently overweight or obesity, as an early signal of metabolic syndrome. Also, our results suggest that ox-LDL has a role independently of insulin resistance effect on metabolic syndrome and ox-LDL reflect the mechanisms by which the components of metabolic syndrome develop and progress.