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

Authors
  • Parikh, Rushi V1
  • Pargaonkar, Vedant2
  • Ball, Robyn L3
  • Kobayashi, Yuhei2
  • Kimura, Takumi2
  • Yeung, Alan C2
  • Cooke, John P4
  • Tremmel, Jennifer A5
  • 1 Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, United States of America. , (United States)
  • 2 Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States of America. , (United States)
  • 3 Quantitative Sciences Unit, Division of Biomedical Informatics Research, Stanford University, Palo Alto, CA, United States of America. , (United States)
  • 4 Department of Cardiovascular Sciences, Texas Methodist Research Institute, Houston, TX, United States of America. , (United States)
  • 5 Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States of America. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
International journal of cardiology
Publication Date
Jan 15, 2020
Volume
299
Pages
7–11
Identifiers
DOI: 10.1016/j.ijcard.2019.07.062
PMID: 31416658
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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). 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. Copyright © 2019 Elsevier B.V. All rights reserved.

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