Association between Oxidative Burden and Restenosis: A Case-Control Study

Abstract

Background. In-stent restenosis (ISR) is an important clinical complication that occurs following stent implantation. The application of drug-eluting stents (DES) and even consumption of drugs such as antiplatelet agents and statins are not completely effective in reducing ISR risk. Since the number of these patients continues to rise, it is pivotal to detect patients who are at a higher risk of ISR. In addition, identification of biochemical markers of ISR could give the right perspective on choosing the proper strategy to treat these patients. Several pathophysiological pathways including oxidative stress (OS) are implicated in the progression of ISR. Hence, this study aimed to evaluate the association between oxidative/anti-oxidative markers and ISR. Methods. This was a case-control study which comprised 21 ISR, 26 NISR (non-ISR), and 20 healthy subjects. The serum levels of OS markers including malondialdehyde (MDA), thiol groups (GSH), total antioxidant capacity (TAC), and the activity of serum antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed by colorimetric methods. The overall oxidative burden was assessed using a pro-oxidant-antioxidant balance (PAB) assay. Results. MDA levels were considerably higher in the ISR group when compared to healthy subjects ( $P=0.004$ ). PAB also indicated significantly higher values in both ISR ( $P<0.001$ ) and NISR ( $P<0.001$ ) groups related to healthy subjects. No significant differences were observed between the studied groups regarding thiol levels, antioxidant enzyme activities, and TAC. Multinomial logistic regression analysis showed that elevated serum levels of MDA (OR: 1.028, 95% CI: 1.008-1.048; $P=0.006$ ) and PAB (OR: 1.076, 95% CI: 1.017-1.139; $P=0.011$ ) were significantly associated with higher ISR risk; however, increased values of TAC (OR: 0.990, 95% CI: 0.982-0.999; $P=0.030$ ) were significantly associated with decreased ISR risk, while after adjustment for confounders, only SOD activity (OR: 0.0, 95% CI: 0.0-0.0; $P<0.001$ ) and PAB value (OR: 1.866, 95% CI: 1.856-1.900; $P<0.001$ ) showed association with ISR risk. Conclusion. According to the present findings, some oxidative and antioxidative markers like PAB and SOD activity showed the potential in the prediction of ISR risk.