Background and Purpose
Higher plasma concentrations of the endogenous nitric oxides synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) are associated with increased risk of cardio- 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.
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).
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, body mass index (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).
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.