title: Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease.
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.
  
  
  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.
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Nima
authors.initials: N
authors.lastname: Ghasemzadeh
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Salman
authors.initials: S
authors.lastname: Sher
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Shawn
authors.initials: S
authors.lastname: Arshad
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Yi-an
authors.initials: YA
authors.lastname: Ko
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: A Maziar
authors.initials: AM
authors.lastname: Zafari
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Laurence
authors.initials: L
authors.lastname: Sperling
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.).
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: From Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., D.J.E., S.S., S.A., H.S., A.M.Z., L.S., V.V., D.P.J., A.A.Q.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA (Y.K.); Department of Medicine, Baptist Health South Florida, Miami, FL (E.V.); Department of Epidemiology, Rollins School of Public Health, Atlanta, GA (E.V., V.V.); and Department of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.Z.). aquyyum@emory.edu.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D003545:Cysteine / Q000097:blood; D003553:Cystine / Q000097:blood; D003643:Death; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003553:Cystine; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide
keywords: coronary artery disease; cystine; glutathione; inflammation; mortality; oxidative stress; prognosis; redox; risk