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

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 w...

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Autores principales: Patel, Riyaz S., Ghasemzadeh, Nima, Eapen, Danny J., Sher, Salman, Arshad, Shawn, Ko, Yi-an, Veledar, Emir, Samady, Habib, Zafari, A. Maziar, Sperling, Laurence, Vaccarino, Viola, Jones, Dean P., Quyyumi, Arshed A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722941/
https://www.ncbi.nlm.nih.gov/pubmed/26673559
http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019790
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author Patel, Riyaz S.
Ghasemzadeh, Nima
Eapen, Danny J.
Sher, Salman
Arshad, Shawn
Ko, Yi-an
Veledar, Emir
Samady, Habib
Zafari, A. Maziar
Sperling, Laurence
Vaccarino, Viola
Jones, Dean P.
Quyyumi, Arshed A.
author_facet Patel, Riyaz S.
Ghasemzadeh, Nima
Eapen, Danny J.
Sher, Salman
Arshad, Shawn
Ko, Yi-an
Veledar, Emir
Samady, Habib
Zafari, A. Maziar
Sperling, Laurence
Vaccarino, Viola
Jones, Dean P.
Quyyumi, Arshed A.
author_sort Patel, Riyaz S.
collection PubMed
description 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.
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spelling pubmed-47229412016-02-02 Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease Patel, Riyaz S. Ghasemzadeh, Nima Eapen, Danny J. Sher, Salman Arshad, Shawn Ko, Yi-an Veledar, Emir Samady, Habib Zafari, A. Maziar Sperling, Laurence Vaccarino, Viola Jones, Dean P. Quyyumi, Arshed A. Circulation Original Articles 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. Lippincott Williams & Wilkins 2016-01-26 2016-01-25 /pmc/articles/PMC4722941/ /pubmed/26673559 http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019790 Text en © 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 (http://creativecommons.org/licenses/by-nc/3.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Patel, Riyaz S.
Ghasemzadeh, Nima
Eapen, Danny J.
Sher, Salman
Arshad, Shawn
Ko, Yi-an
Veledar, Emir
Samady, Habib
Zafari, A. Maziar
Sperling, Laurence
Vaccarino, Viola
Jones, Dean P.
Quyyumi, Arshed A.
Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
title Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
title_full Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
title_fullStr Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
title_full_unstemmed Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
title_short Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease
title_sort novel biomarker of oxidative stress is associated with risk of death in patients with coronary artery disease
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722941/
https://www.ncbi.nlm.nih.gov/pubmed/26673559
http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019790
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