Increased reactive oxygen metabolites is associated with cardiovascular risk factors and vascular endothelial damage in middle-aged Japanese subjects

BACKGROUND Vascular endothelium, a provider of nitric oxide, is essential for the maintenance of homeostasis in healthy vascular systems. Increased oxidative stress promotes vascular inflammation and is a common pathway involved in endothelial damage. The present study sought to investigate the usefulness of derivative reactive oxygen metabolites (d-ROM) as an oxidative stress marker for detecting endothelial damage in the clinical setting in subjects with early-stage atherosclerosis. METHODS Study 1 investigated the relationship between serum d-ROM levels and cardiovascular risk factors in apparently healthy middle-aged subjects (n = 1992, 49 ± 8 years) who participated in our health checkup program. Study 2 analyzed the association between d-ROM levels and endothelial function assessed by flow-mediated dilation and that between d-ROM levels and high-sensitivity C reactive protein (hs-CRP) levels in middle-aged outpatients with mild-to-moderate cardiovascular risk (n = 43, 40 ± 5 years). RESULTS In study 1, the d-ROM level was independently correlated with age, systolic blood pressure, fasting plasma glucose, low-density lipoprotein cholesterol, and brain natriuretic peptide in univariate and multivariate regression analysis. In study 2, the d-ROM level was correlated positively with the hs-CRP level and inversely with the flow-mediated dilation value. Patients in the highest tertile of d-ROM had significantly lower flow-mediated dilation values compared with patients in the other tertiles. Moreover, after subdivision of patients into four groups according to d-ROM and hs-CRP levels, patients with high levels of both d-ROM and hs-CRP showed significantly reduced flow-mediated dilation as compared with those with low levels of both indices. CONCLUSION The close relationship of d-ROM with cardiovascular risk factors, brain natriuretic peptide, inflammatory markers (hs-CRP), and endothelial function (flow-mediated dilation) suggest that d-ROM is a useful oxidative stress marker for detection of endothelial damage in the clinical setting. Assessment of d-ROM, especially combined with hs-CRP, may be a possible predictor of cardiovascular disease.