Oxidative markers in spontaneous intracerebral hemorrhage: leukocyte 8-hydroxy-2′-deoxyguanosine as an independent predictor of the 30-day outcome

Abstract

Object Oxidative stress may play a role in spontaneous intracerebral hemorrhage (ICH), but data on oxidative burden in cerebral hemorrhage are limited, and it is not clear whether oxidative markers add predictive power regarding ICH outcome beyond that of traditional factors. The authors therefore examined redox status and traditional factors in ICH patients within 3 days of hemorrhage onset to delineate redox status in ICH and investigate the predictive value with respect to 30-day functional outcome. Methods Sixty-four patients with ICH and 114 controls were prospectively enrolled in this study. Blood samples were collected within 3 days of ICH onset and processed for isolation of plasma, erythrocytes, and leukocytes. The authors evaluated levels or activities of leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG), erythrocyte glucose-6-phosphate dehydrogenase (G6PD), erythrocyte glutathione peroxidase (GPx), plasma malondialdehyde (MDA), vitamin E, and vitamin A, as well as traditional factors including the presence of hypertension or diabetes mellitus, total cholesterol level, and measures of liver function. A general linear model and multivariable logistic regression were used for analyses where appropriate. Results After adjustment for age and sex and traditional risk factors, ICH was significantly associated with an increased level of 8-OHdG (p < 0.0001), decreased GPx activity (p = 0.0002), and a decreased level of vitamin E (p = 0.003). There was no association of ICH risk with G6PD activity or MDA or vitamin A level. Considering all the oxidative markers and traditional risk factors together, logistic regression showed an independent association of ICH with 8-OHdG (OR 2.7, 95% CI 1.7–4.2, p < 0.0001). The association between increased 8-OHdG level and lower 30-day Barthel Index was also independent of the effects of age, sex, hemorrhage location and size, and traditional factors (p = 0.026). Unfavorable outcome (modified Rankin Scale score ≥ 3) at 30 days after ICH onset was not significantly associated with any of the examined oxidative markers. Conclusions Increased leukocyte 8-OHdG levels, as well as decreased GPx activity and vitamin E levels, were found during acute ICH. Only 8-OHdG was associated with ICH and the 30-day outcome independently from the other oxidative markers and traditional factors. Leukocyte 8-OHdG may add power beyond the traditional factors in predicting ICH outcome and thus may be used as an independent surrogate for clinical ICH study.