Association of oxidative stress with mortality: the Beaver Dam Eye Study.

Epidemiological studies have shown that oxidative stress is associated with cardiovascular disease (CVD) and diabetes. However, the association of oxidative stress marker with non-CVD and CVD mortality has not been extensively evaluated. The association of baseline serum 8-isoprostane (8-ISO) with all-cause, non-CVD, and CVD mortality was examined in a random subset (n = 1,753) of a population-based study of 4,926 adults (99% non-Hispanic whites; 56% women) aged 43-86 years from the Beaver Dam Eye Study. Cause of death was ascertained by death certificate between 1987 and 2002. 8-ISO was measured by immunoassay. Cox proportional hazards regression analysis was used to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs) by one 8-ISO standard deviation. During a median follow-up of 13.1 years, 590 (33.7%) participants died (290 CVD deaths). After adjusting for socio-demographics and CVD risk factors, 8-ISO was significantly associated with all-cause (HR = 1.1, 95% CI 1.01-1.2) and non-CVD (HR = 1.14, 95% CI 1.01-1.28) mortality but not with CVD mortality (HR = 1.06, 95% CI 0.93-1.2). When limited to participants with BMI < 25 kg/m2, individuals in the highest 8-ISO quartile had approximately 34 to 36% increased risk of all-cause, non-CVD, and CVD death compared to those at the lowest quartile. In contrast, 8-ISO was not significantly associated with mortality among those with BMI ≥ 25 kg/m2. These findings suggest that baseline serum 8-ISO, a marker of oxidative stress, is an independent risk factor of all-cause, non-CVD, and CVD mortality among a cohort of middle-aged adults with normal BMI.