title: Association of the endogenous nitric oxide synthase inhibitor ADMA with carotid artery intimal media thickness in the Framingham Heart Study offspring cohort.
abstract: OBJECTIVE
  Higher plasma concentrations of the endogenous nitric oxides synthase inhibitor asymmetrical dimethylarginine (ADMA) are associated with increased risk of cardiovascular and cerebrovascular events and death, presumably by promoting endothelial dysfunction and subclinical atherosclerosis. We hypothesized that plasma ADMA concentrations are positively related to common carotid artery intimal-media thickness (CCA-IMT) and to internal carotid (ICA)/bulb IMT.
  
  
  METHODS
  We investigated the cross-sectional relations of plasma ADMA with CCA-IMT and ICA/bulb IMT in 2958 Framingham Heart Study participants (mean age, 58 years; 55% women).
  
  
  RESULTS
  In unadjusted analyses, ADMA was positively related to both CCA-IMT (beta per SD increment, 0.012; P<0.001) and ICA/bulb IMT (beta per SD increment, 0.059; P<0.001). In multivariable analyses (adjusting for age, sex, systolic blood pressure, antihypertensive treatment, smoking status, diabetes, BMI, total-to-HDL cholesterol ratio, log C-reactive protein, and serum creatinine), plasma ADMA was not associated with CCA-IMT (P=0.991), but remained significantly and positively related to ICA/bulb IMT (beta per SD increment, 0.0246; P=0.002).
  
  
  CONCLUSIONS
  In our large community-based sample, we observed that higher plasma ADMA concentrations were associated with greater ICA/bulb IMT, but not with CCA-IMT. These data are consistent with the notion that ADMA promotes subclinical atherosclerosis in a site-specific manner, with a greater proatherogenic influence at known vulnerable sites in the arterial tree.
authors.affiliation: Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Vanessa
authors.initials: V
authors.lastname: Xanthakis
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sullivan
authors.forename: Ralf
authors.initials: R
authors.lastname: Benndorf
authors.forename: Friedrich
authors.initials: F
authors.lastname: Schulze
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D032721:Adult Children; D000368:Aged; D001120:Arginine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood* / Q000201:enzymology* / Q000473:pathology; D017536:Carotid Artery, Common / Q000201:enzymology / Q000473:pathology; D002343:Carotid Artery, Internal / Q000201:enzymology / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000378:metabolism; D017539:Tunica Intima / Q000201:enzymology / Q000473:pathology*; D017540:Tunica Media / Q000201:enzymology / Q000473:pathology*
chemical_list: D015415:Biomarkers; C487735:dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase