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

• Type of Material: Article
• Authors: Riyaz S. Patel, Emory University; Nima Ghasemzadeh, Emory University; Danny Eapen, Emory University; Salman Sher, Emory University; Shawn Arshad, Emory University; Yi-An Ko, Emory University; Emir Veledar, Emory University; Habib Samady, Emory University; Abarmard Zafari, Emory University; Laurence Sperling, Emory University; Laura Vaccarino, Emory University; Dean Jones, Emory University; Arshed Quyyumi, Emory University
• Language: English
• Date: 2016-01-26
• Publisher: American Heart Association
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Authors.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019790
• Title of Journal or Parent Work: Circulation
• ISSN: 0009-7322
• Volume: 133
• Issue: 4
• Start Page: 361
• End Page: 369
• Grant/Funding Information: R.S.P. was supported by an American Heart Association postdoctoral fellowship while data were being collected and currently by a British Heart Foundation intermediate clinical fellowship (UK); A.A.Q. has been supported by National Institutes of Health (NIH) grants 5P20HL113451-01, 5P01HL101398-02, 1R56HL126558-01, 1U10HL110302-01, and U01 HL-079156; D.P.J. was supported by HL113451, ES 009047, AG038746, ES019776, and HHSN272201200031C.; Funding for collection and management of samples was received from the Robert W. Woodruff Health Sciences Center Fund (Atlanta, GA), Emory Heart and Vascular Center (Atlanta, GA), Katz Family Foundation Preventive Cardiology Grant (Atlanta, GA), and in part by NIH grants UL1 RR025008 and R01HL089650-02 from the Clinical and Translational Science Award program.
• Keywords: CARDIOVASCULAR-DISEASE; EARLY ATHEROSCLEROSIS; mortality; Life Sciences & Biomedicine; cystine; Cardiac & Cardiovascular Systems; GLUTATHIONE; prognosis; Science & Technology; FOLIC-ACID; redox; PREVENTION; glutathione; risk; HEALTHY-ADULTS; Cardiovascular System & Cardiology; REDOX STATE; coronary artery disease; Peripheral Vascular Disease; MYOCARDIAL-INFARCTION; HUMAN PLASMA; inflammation; RANDOMIZED-TRIAL; oxidative stress

Abstract

BACKGROUND—: Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free 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 & <-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to 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 hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS—: A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress.