Abstract 17062: Plasma Asymmetric Dimethylarginine Levels Correlate with Peripheral Arterial Disease Severity but not Coronary Artery Disease
Plasma levels of Asymmetric Dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase causally linked to endothelial dysfunction, is associated with increased cardiovascular events in population-based studies and has been postulated as 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: As part of a prospective multicenter study, subjects referred for cardiac catheterization (n=510; age=66+/-10, male=66%) underwent clinical evaluation, coronary angiography and measurement of plasma ADMA levels and Ankle Brachial Indices (ABI). Coronary angiograms were analysed for CAD severity (number of vessels with > 60% stenosis) and modified Gensini score.
Results: Plasma ADMA was positively correlated with diastolic blood pressure (p=0.001), low density lipoprotein level (p=0.048) and hypercholesterolaemia (p=0.012), but negatively correlated with glomerular filtration rate (p=0.011). ADMA levels correlated with PAD (ABI <0.9) OR= 3.7 (95% CI 1.5 to 8.8, p=0.004) on univariate analysis. Plasma ADMA was significantly negatively correlated with ABI (coefficient -0.17, 95% CI -0.26 to -0.86, p<0.001). The association remained significant after adjustment for cardiovascular risk factors (coefficient -0.14, 95% CI -0.05 to -0.23, p=0.003). By contrast, plasma ADMA was not associated with CAD severity (coefficient -0.459, CI -0.969 to 0.051, p=0.078) or Gensini score (Coefficient -0.24, 95% CI -0.85 to 0.37, p=0.44) despite significant correlations between major traditional CAD risk factors and angiographic CAD severity.
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.
- © 2012 by American Heart Association, Inc.