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Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease

Patel, RS; Ghasemzadeh, N; Eapen, DJ; Sher, S; Arshad, S; Ko, YA; Veledar, E; ... Quyyumi, AA; + view all (2016) Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease. Circulation , 133 (4) pp. 361-369. 10.1161/CIRCULATIONAHA.115.019790. Green open access

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Abstract

BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 ± 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (>+1 SD and <-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

Type: Article
Title: Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCULATIONAHA.115.019790
Publisher version: http://dx.doi.org/10.1161/CIRCULATIONAHA.115.01979...
Language: English
Additional information: Copyright © 2015 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.
Keywords: coronary artery disease, cystine, glutathione, inflammation, mortality, oxidative stress, prognosis, redox, risk
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1483575
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