Evaluation of Oxidative Stress Status in Familial Hypercholesterolemia

Abstract

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), thiol (p < 0.001), NO (p < 0.01), and PAB (p < 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (p < 0.001) and PAB (p < 0.001) when compared to healthy subjects. Elevated levels of MDA (p < 0.001) and PAB (p < 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979; p = 0.033), and MDA (OR: 0.996; p = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished. Conclusion: Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.