Association of the endogenous nitric oxide synthase inhibitor ADMA with carotid artery intimal media thickness in the Framingham Heart Study offspring cohort.
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.
Maas
Renke
R
Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
Xanthakis
Vanessa
V
Polak
Joseph F
JF
Schwedhelm
Edzard
E
Sullivan
Lisa M
LM
Benndorf
Ralf
R
Schulze
Friedrich
F
Vasan
Ramachandran S
RS
Wolf
Philip A
PA
Böger
Rainer H
RH
Seshadri
Sudha
S
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*
D015415:Biomarkers; C487735:dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase