title: Association of endothelial and oxidative stress with metabolic syndrome and subclinical atherosclerosis: multi-ethnic study of atherosclerosis.
abstract: OBJECTIVE
  A cluster of metabolic abnormalities termed metabolic syndrome (MetS) is associated with vascular endothelial dysfunction and oxidative internal milieu. We examined whether the association of MetS with subclinical atherosclerosis is explained by biomarkers of endothelial damage and oxidative stress.
  
  
  METHODS
  Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of 45- to 84-year-old individuals of four US ethnicities without clinical cardiovascular disease. A random sample of 997 MESA participants had data on the following biomarkers: von Willebrand factor, soluble intercellular adhesion molecule-1 (sICAM-1), CD40 ligand (CD40L), soluble thrombomodulin, E-selectin and oxidized LDL (oxLDL). We examined whether the associations of MetS with B-mode ultrasound-defined common and internal carotid intimal-medial thickness (IMT) and coronary artery calcium (CAC) measured using computerized tomography were explained by the biomarkers using multiple regression methods.
  
  
  RESULTS
  MetS was associated with higher levels of each of the biomarkers (P<0.001, CD40L-suggestive association P=0.004), with greater IMT (P<0.001), and with greater extent of CAC in those in whom CAC was detectable (P=0.01). The association of MetS with measures of subclinical atherosclerosis remained unchanged after adjustment for the biomarkers. After adjusting for MetS, oxLDL was suggestively associated with greater prevalence of detectable CAC (P=0.005) and thicker internal carotid IMT (P=0.002), whereas sICAM-1 was significantly associated with greater prevalence of detectable CAC (P=0.001).
  
  
  CONCLUSIONS
  The association of MetS with subclinical atherosclerosis was independent of its association with biomarkers of endothelial damage and oxidative stress, suggesting that metabolic abnormalities and oxidative endothelial damage may lead to atherosclerotic disease through distinct mechanisms.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. dvaidya1@jhmi.edu
authors.forename: D
authors.initials: D
authors.lastname: Vaidya
authors.forename: M
authors.initials: M
authors.lastname: Szklo
authors.forename: M
authors.initials: M
authors.lastname: Cushman
authors.forename: P
authors.initials: P
authors.lastname: Holvoet
authors.forename: J
authors.initials: J
authors.lastname: Polak
authors.forename: H
authors.initials: H
authors.lastname: Bahrami
authors.forename: N S
authors.initials: NS
authors.lastname: Jenny
authors.forename: P
authors.initials: P
authors.lastname: Ouyang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000175:diagnosis / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000453:epidemiology / Q000209:etiology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D018384:Oxidative Stress; D015995:Prevalence; D012720:Severity of Illness Index; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1