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(Stroke. 2009;40:2715.)
© 2009 American Heart Association, Inc.

Original Contributions

Association of the Endogenous Nitric Oxide Synthase Inhibitor ADMA With Carotid Artery Intimal Media Thickness in the Framingham Heart Study Offspring Cohort

Renke Maas, MD; Vanessa Xanthakis, MS; Joseph F. Polak, MD; Edzard Schwedhelm, PhD; Lisa M. Sullivan, PhD; Ralf Benndorf, MD; Friedrich Schulze, PhD; Ramachandran S. Vasan, MD; Philip A. Wolf, MD; Rainer H. Böger, MD Sudha Seshadri, MD

From Institute for Experimental and Clinical Pharmacology and Toxicology (R.M.), University Erlangen-Nuremberg, Germany; Clinical Pharmacology Unit (R.M., E.S., R.B., F.S., R.H.B.), Institute of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Germany; Department of Biostatistics (V.X., L.M.S.), Boston University School of Public Health, Boston, Mass; Department of Radiology (J.F.P.), Tufts-New England Medical Center, Boston, Mass; The National Heart, Lung, and Blood Institute’s Framingham Heart Study (L.M.S., R.S.V., P.A.W., S.S.), Framingham, Mass; Department of Neurology (R.S.V., P.A.W., S.S.), School of Medicine, Boston University, Boston, Mass.

Correspondence to Sudha Seshadri, MD, DM, Associate Professor, Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118. E-mail suseshad{at}bu.edu

Background and Purpose— 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 (β per SD increment, 0.012; P<0.001) and ICA/bulb IMT (β 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 (β 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.

Key Words: carotid intimal medial thickness • epidemiology • risk factors

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