Abstract 13916: A Novel Biomarker of Oxidative Stress is Predictive of Incident Death and Myocardial Infarction in Patients with Coronary Artery Disease
Introduction: Oxidative stress (OS) is implicated in cellular damage and atherosclerosis, yet clinical experience of free radical scavengers has been uniformly disappointing, promoting the concept that clinically important OS may be mediated by alternative non-free radical processes.
Hypothesis: We hypothesized that novel aminothiol markers of non-free radical mediated OS would predict incident adverse outcomes in patients at high risk for CAD
Methods: 1411 consecutive patients undergoing coronary angiography (mean age 63 years, male 66%), were recruited from the Emory Cardiovascular Biobank study. Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were measured by high performance liquid chromatography at baseline and patients followed prospectively for a primary composite endpoint of death or non-fatal MI.
Results: During a mean follow up of 3.9± 2.2 years, 19% died or suffered a non-fatal MI. The adjusted hazard ratios for all cause death/MI based on high vs low cut-points for the oxidized disulphide cystine was 1.65 (95% CI, 1.27-2.15); for reduced glutathione was 0.69 (0.52-0.92), and for the ratio of cystine/glutathione was 1.79 (1.39-2.30). Compared to a model containing clinical risk factors and CRP, addition of the cystine/glutathione ratio improved the C-Statistic (p=0.03) and also correctly reclassified 17% of events and 23% of non-events. When combined with high/low CRP into a 3 level multi-marker score, those with 2 high markers had an annualized event rate of 12.8% compared to 4.5% and 1.4% for those with 1 raised marker or none, respectively. Similar associations were found for all-cause and cardiovascular death endpoints and also in stratified analysis for those with and without significant CAD.
Conclusions: A high extracellular oxidant burden and reduced intracellular antioxidant capacity quantified by the plasma aminothiols, cystine, glutathione and their respective ratio, is associated with adverse events in patients with CAD, a finding that is independent of and additive to any inflammatory burden. Further studies are needed to validate these findings, which support an alternative model of oxidative stress independent of free radical biology.
Author Disclosures: R.S. Patel: None. N. Ghasemzadeh: None. D.J. Eapen: None. S. Sher: None. S. Arshad: None. E. Veledar: None. H. Samady: None. A. Zafari: None. L. Sperling: None. V. Vaccarino: None. D.P. Jones: None. A.A. Quyyumi: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.