4.8 Article

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

期刊

CIRCULATION
卷 133, 期 4, 页码 361-369

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.115.019790

关键词

coronary artery disease; cystine; glutathione; inflammation; mortality; oxidative stress; prognosis; redox; risk

资金

  1. American Heart Association postdoctoral fellowship
  2. British Heart Foundation intermediate clinical fellowship (UK)
  3. National Institutes of Health (NIH) [5P20HL113451-01, 5P01HL101398-02, 1R56HL126558-01, 1U10HL110302-01, U01 HL-079156]
  4. Robert W. Woodruff Health Sciences Center Fund (Atlanta, GA)
  5. Emory Heart and Vascular Center (Atlanta, GA)
  6. Katz Family Foundation Preventive Cardiology Grant (Atlanta, GA)
  7. NIH grants from the Clinical and Translational Science Award program [UL1 RR025008, R01HL089650-02]
  8. [HL113451]
  9. [ES 009047]
  10. [AG038746]
  11. [ES019776]
  12. [HHSN272201200031C]
  13. British Heart Foundation [FS/14/76/30933] Funding Source: researchfish

向作者/读者索取更多资源

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 4.72.1 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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