Abstract 3631: Plasma Asymmetric Dimethylarginine is an Independent Marker of Peripheral Artery Disease but not Coronary Artery Disease: A Novel Marker of Atherosclerosis with Topographical Specificity
Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase causally linked to endothelial dysfunction, are elevated in those with risk factors for atherosclerosis and may be a novel risk factor for atherosclerosis. We sought to study the relationship between plasma ADMA and atherosclerosis as manifest by peripheral artery disease (PAD) and coronary artery disease (CAD).
Methods and Results: As part of a prospective multicenter study, subjects referred for cardiac catheterization (n =280; age, 66±1 years; male patients: 57%) underwent clinical evaluation, determination of serum chemistries and ADMA levels, coronary angiography and measurement of ankle brachial indices (ABI). Coronary angiograms were analysed for CAD severity (number of vessels with > 60% stenosis) and modified Gensini score. Univariate and multivariate analyses revealed that plasma ADMA was positively correlated with body mass index (P<0.001), mean arterial pressure (P=0.03) and presence of diabetes mellitus (P=0.04) but negatively correlated with glomerular filtration rate (P<0.001). ADMA levels were elevated in PAD patients (defined by ABI<0.9)(0.63±0.03μmol/L) compared to those without PAD (0.55±0.01μmol/L)(P=0.03). Plasma ADMA was significantly negatively correlated with ABI on both univariate analysis (r=−0.26, P<0.001) and on multivariate analysis (P<0.001). By contrast, ADMA levels in those with normal coronary angiograms (0.55±0.05μmol/L) were similar to those with significant 1-to-3 vessel CAD (0.56±0.02μmol/ L)(P=0.8). Plasma ADMA levels were not correlated with either CAD severity (r=−0.08, P=0.16) or modified Gensini score (r=−0.05; P=0.44), despite significant correlations between all major traditional CAD risk factors (hypertension, hypercholesterolemia, age, gender and smoking) and both CAD severity and modified Gensini score in our study cohort. Findings for ADMA and CAD were unchanged in multivariate analysis.
Conclusion: Plasma ADMA is independently correlated with PAD severity, but has no correlation with angiographic CAD severity. ADMA may be a novel differential marker for atherosclerosis - a finding with implications for understanding topographic differences in atherogenesis.