Patients with rheumatoid arthritis (RA) are predisposed to atherosclerosis and cardiovascular disease. This is thought to be caused in part, by exposure to chronic systemic inflammation during the course of the disease. We hypothesized that RA disease duration augments the effect of age on atherosclerosis. We measured the carotid artery intima-media thickness (IMT) in 631 consecutive RA patients. We ascertained age, sex and disease duration, established CV risk factors, RA clinical manifestations and markers of inflammation. We used multivariable regression to model IMT, with age as the independent variable. We then added RA duration quartile x age interaction terms to estimate the IMT-age relationship within RA duration strata. We found that the rate at which the IMT increased per unit of age steepened in proportion to the RA duration, from 0.154 mm/10 years among patients with RA for 7 years or less, to 0.295 mm/10 years among patients with RA for 20 years or more (P<or=0.001). None of the covariates effaced the significance of the age x RA duration product terms. Thus, patients with prolonged RA have more atherosclerosis than patients of the same age with more recent disease onset. This suggests that atherogenesis accelerates after the onset of RA. Systemic inflammation may amplify the age-related risk of CV disease.