Oxidative Stress Markers and the Risk of Incident Stroke and Ischemic Heart Disease: A Case-Cohort Study

Background and Purpose: To investigate the association between derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP) and the risk of stroke by subtype, and ischemic heart disease (IHD). Methods: We employed a case cohort design consisting of cardiovascular disease cases (n=1,521; stroke, n=1,271; IHD, n=265) and a random sub-cohort (n=4,761) in a large Japanese population-based study. d-ROMs and BAP were measured in plasma samples collected between 1995 and 1999. Hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods according to d-ROMs and BAP quartiles, adjusted for age, sex, area, and potential confounding factors. Results: Analysis revealed a positive association between d-ROMs and the risk of total stroke, ischemic stroke, IHD, and the composite outcome of ischemic stroke and IHD. The multivariable HRs and 95% confidence intervals (CIs) for the highest versus lowest quartiles for d-ROMs were 1.34 (95% CI: 1.11-1.63) for total stroke (P for trend<0.001), 1.47 (1.16-1.86) for ischemic stroke (P for trend<0.001), 1.47 (1.02-2.11) for IHD (P for trend=0.072), 1.47 (0.87-2.49) for subarachnoid hemorrhage (P for trend=0.101), and 1.01 (0.72-1.41) for intraparenchymal hemorrhage (P for trend=0.618). In contrast, no significant association was detected between BAP levels and the risk of cardiovascular disease. Conclusions: Analysis revealed that d-ROMs levels were positively associated with the risk of ischemic stroke and heart disease but not with hemorrhagic stroke.