Association of oxidative DNA damage and C-reactive protein in women at risk for cardiovascular disease.

OBJECTIVE: The aim of the current study was to examine the relationship between clinical markers of inflammation and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG), an oxidative stress marker, in middle-aged women drawn from the HANDLS study, a longitudinal epidemiological study. METHODS AND RESULTS: We examined commonly assayed markers of inflammation, the DNA base adduct 8-oxodG, a marker of oxidative stress, and cardiovascular risk factors in a cohort of women matched on age and race in 3 groups (n=39 per group) who had low (<3 mg/L) high-sensitivity C-reactive protein (hsCRP), mid (>3-20 mg/L), and high (>20 mg/L) hsCRP. We found a significant relationship between hsCRP level and the oxidative stress marker, 8-oxodG. 8-oxodG was positively correlated with systolic blood pressure, pulse pressure, and interleukin-23. hsCRP was associated with obesity variables, high-density lipoprotein, serum insulin levels, interleukin-12p70 and intracellular adhesion molecule-1. Incubation of primary human endothelial cells with hsCRP generated reactive oxygen species in vitro. Furthermore, hsCRP specifically induced DNA base lesions, but not other forms of DNA damage, including single and double strand breaks. CONCLUSIONS: These data suggest that in women 8-oxodG is associated with hsCRP and is independently related to select cardiovascular risk factors. Our data in women suggest that hsCRP may contribute to cardiovascular disease by increasing oxidative stress.