Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease

Qurratu Aini Musthafa, Muhd Faizan Abdul Shukor, Noor Akmal Shareela Ismail, Azmee Mohd Ghazi, Rosli Mohd Ali, Ika Faizura M. Nor, Mohd Zamrin Dimon, Wan Zurinah Wan Ngah

Identifying patients at risk of developing premature coronary artery disease (PCAD) which occurs at age below 45 years old and constitutes approximately 7-10% of coronary artery disease (CAD) worldwide remains a problem. Oxidative stress has been proposed as a crucial step in the early development of PCAD. This study was conducted to determine the oxidative status of PCAD in comparison to CAD patients. PCAD (<45 years old) and CAD (>60 years old) patients were recruited with age-matched controls (n=30, each group). DNA damage score, plasma malondialdehyde (MDA) and protein carbonyl content were measured for oxidative damage markers. Antioxidants such as erythrocyte glutathione (GSH), oxidized glutathione (GSSG) and glutathione peroxidase activity (GPx), superoxide dismutase (SOD) and catalase (CAT) were also determined. DNA damage score and protein carbonyl content were significantly higher in both PCAD and CAD when compared to age-matched controls while MDA level was increased only in PCAD (p<0.05). In contrast, GSH, GSH/GSSG ratio, α-tocotrienol isomer and GPx activity were significantly decreased but only in PCAD when compared to age-matched controls. The decrease in GSH was associated with PCAD (OR=0.569 95%CI [0.375-0.864], p=0.008) and cut-off values of 6.69 μM with areas under the ROC curves (AUROC) 95%CI: 0.88 [0.80-0.96] (sensitivity of 83.3%; specificity of 80%). However, there were no significant differences in SOD and CAT activities in all groups. A higher level of oxidative stress indicated by elevated MDA levels and low levels of GSH, α-tocotrienol and GPx activity in patients below 45 years old may play a role in the development of PCAD and has potential as biomarkers for PCAD.