title: Increased reactive oxygen metabolites is associated with cardiovascular risk factors and vascular endothelial damage in middle-aged Japanese subjects.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. tomosugi@med.nagoya-cu.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Dohi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takase
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Yamashita
authors.forename: Satoru
authors.initials: S
authors.lastname: Tanaka
authors.forename: Genjiro
authors.initials: G
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007564:Japan; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D018836:Inflammation Mediators; D008055:Lipids; D017382:Reactive Oxygen Species; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein