Findings of this hospital-based case control study demonstrated that TAC levels despite MDA levels, which were higher in patients with stroke, were lower in this group. Also, it showed that MDA levels is a better predictor of stroke development than TCA, while none of these measures was significantly associated with having risk factors for stroke. Furthermore, we found a negative correlation between clinical tools, NIHSS and mRS, and chemical measures, TAC and MDA.
Numerous studies have investigated the TAC and MDA levels in stroke patients and showed that serum TAC levels in stroke cases were significantly lower (20, 21) and MDA levels were higher than the control group (22, 23). A case-control study on 195 hospitalized cases with stroke and 195 healthy controls in Iranian populations which were categorized into three groups showed that the top tertile of dietary TAC had lower chance to have stroke than the bottom tertile (OR = 0.49 (95% CI: 0.23, 1.00)), although our study revealed a significant protective association between the bottom quartile of TCA and stroke (OR = 0.29 (95% CI: 0.09–0.94)) (24). The discrepancy might be due to different methods for determining categories. Moreover, the article by Guldiken et al. which categorized participants into diabetic stroke, nom-diabetic stroke, and healthy controls showed that TAC levels were significantly higher in diabetic acute stroke patients than in non-diabetic ones (10.03 vs. 5.97 mM; P < 0.001) and was higher in diabetic patients with stroke compared to control group (10.03 vs. 5.44 mM; P < 0.001) (25). Opara et al. found that the total antioxidant capacity was depleted in the diabetic patients compared to normal subjects (26). On the contrary, Savu et al. showed that the TAC of plasma, despite of high oxidative stress levels, was increased in patients with uncomplicated type Ⅱ diabetes (27). In the present study, the TAC levels of the patient at risk of stroke did not show any significant difference from control group, whereas it was higher than the stroke patients and healthy group, which might be due to the different assays for determination of TAC.
The study by Al-Rawi et al. conducted on 50 patients with ischemic stroke, 75 participants with a risk factor for stroke, including diabetes, hypertension, and ischemic heart disease, and 25 healthy individuals. MDA levels were measured in the serum and saliva of subjects and showed that MDA levels in both groups were significantly higher than the healthy group (P < 0.001) (28). Our findings confirmed that MDA has a significant increasing association with stroke occurrence, while this association was not significant in patients who were at risk of stroke. We propose that significant increase in MDA level in stroke is a reflection of increased MDA production and oxidative stress in cerebral ischemia since the top quartile of MDA was in higher risk of stroke compared to the bottom quartile, although they were not significant.
A case-control study on 50 patients with stroke and 50 healthy controls represented higher levels of MDA in cases than controls (3.31 vs. 1.62 nmol/ml; P < 0.0001) (29). In this regard, the article by Bir et al. showed significantly greater MDA values in both atherothrombotic ischemic stroke and with lacunar infarction compared to healthy controls (P < 0.001) (30). It has been suggested that blood or neural lipids may be the source of lipid peroxidation caused by ischemia. In addition, during ischemia, increased cytosolic calcium leads to the activation of phospholipases and proteases, which leading to conversion of xanthine dehydrogenase to xanthine oxidase or activation of protein kinase. Consequently, these activated enzymes can also be the cause of the increased free radicals (31).
This study also compared the correlation between TAC or MDA with NIHSS-baseline, NIHSS-follow-up, mRS-discharge, and mRS-follow-up. A cohort study on 42 patients with acute ischemic stroke found no significant association between severity of stroke based on baseline NIHSS and level of MDA (P = 0.60), whereas there was a significant positive correlation between level of MDA and mRS after three months of follow-up (r = 0.54; P = 0.001) (32). In addition, Yaseen et al. revealed that level of MDA on the 7th day had a positive correlation with NIHSS and mRS scores at 7th day (r = 0.335; P = 0.024 for NIHSS and r = 0.342; P = 0.022) (33). We found a negative correlation between levels of MDA and TAC and NIHSS and mRS. Our findings is in accordance with a study on 34 ischemic stroke patients and 34 healthy controls that showed a negative correlation between total antioxidant status (TAS) and NIHSS values, even though it was not significant (r= -0.17; P = 0.34) (34). Moreover, another study on acute ischemic stroke patients and healthy controls showed that TAC levels were negatively correlated with NIHSS scores (r= -0.38; P = 0.02) (21). The differences in results of our study with mentioned articles can be due to differences in methods of measurement of factors, especially oxidative stress parameters, time to assess the values, and study participants.
The strength of this study is that it is among pioneer studies which included a group of participants who were potentially at risk of having stroke, while several previous studies compared serum levels of oxidative markers only between stroke cases and healthy controls. However, our study had some limitations. First, we adjusted multiple logistic regression test by age, sex, and BMI, while other potential confounding and risk factors, especially atrial fibrillation for stroke were not included in our analysis (35). Second, selection and recall bias could have influenced the results because of susceptibility of case-control studies. Third, we could not reach to a cause-effect relationship because of observational design of this study. Fourth, body composition might have effects on inflammatory factors (36), while the study did not include data on some body composition components measures such as fat mass.