Asymmetric dimethylarginine predicts impaired epicardial coronary vasomotion in patients with angina in the absence of obstructive coronary artery disease

Background: Impaired epicardial coronary vasomotion is a potential mechanism of angina and a predictor of adverse cardiovascular outcomes in patients without angiographic evidence of obstructive coronary artery disease (CAD). We sought to evaluate the association of asymmetric dimethylarginine (ADMA)—a marker of nitric oxide-mediated vascular dysfunction—with epicardial coronary vasomotor dysfunction in this select population. Methods: Invasive testing for epicardial vasomotor dysfunction was performed using intracoronary acetylcholine in the left anterior descending coronary artery. Impaired vasomotor response was defined as a luminal constriction of >20% on quantitative coronary angiography. Plasma ADMA levels were measured using high performance liquid chromatography. A robust multivariate linear mixed-effect model approach and Akaike information criterion were used to determine predictors of vasomotor dysfunction. Results: In 191 patients with angina in the absence of obstructive CAD, abnormal epicardial vasomotion was observed in 137 (71.7%) patients. Median ADMA rose as the extent of impairment progressed: none (0.48 [0.44–0.59] μM), any (0.51 [0.46–0.60] μM, p = 0.12), focal (0.54 [0.49,0.61] μM, p = 0.17), and diffuse (0.55 [0.49,0.63] μM, p = 0.02). In unadjusted analysis, ADMA was highly predictive of vasomotor dysfunction (χ²=15.1, p = 0.002). Notably, ADMA remained a significant predictor even after adjusting for other factors in the best fit model (χ²=10.0, p = 0.02). Conclusions: ADMA is an independent predictor of epicardial coronary vasomotor dysfunction in patients with angina in the absence of obstructive CAD. These data support a very early mechanistic role of ADMA in the continuum of atherosclerotic heart disease.