Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease.
Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease.
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DOI：
10.1161/circulationaha.115.019790
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发表时间：
2016-01-26
期刊：
影响因子：
37.8
通讯作者：
Quyyumi AA
中科院分区：
文献类型：
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作者：
Patel RS;Ghasemzadeh N;Eapen DJ;Sher S;Arshad S;Ko YA;Veledar E;Samady H;Zafari AM;Sperling L;Vaccarino V;Jones DP;Quyyumi AA
补充数字内容可在文本中找到。自由基清除剂未能改善患者的预后，这促进了临床重要的氧化应激可能由其他机制介导的概念。我们试图研究非自由基介导氧化应激的新出现的氨基硫醇标记物与临床结果的关系。采用高效液相色谱法对1411例接受冠状动脉造影的患者（平均年龄63岁，男性66%）血浆中还原（半胱氨酸和谷胱甘肽）和氧化（半胱氨酸和谷胱甘肽二硫化）氨基硫醇的水平进行定量分析。所有患者平均随访4.7±2.1年，主要结局为全因死亡（n=247）。在协变量调整前后，胱氨酸（氧化）和谷胱甘肽（还原）水平与死亡风险相关（P<0.001）。高胱氨酸水平和低谷胱甘肽水平（分别为>+1 SD和< - 1 SD）与较高的死亡率相关（校正风险比[HR]为1.63；95%可信区间[CI]为1.19-2.21；HR为2.19；95% CI为1.50-3.19）。此外，胱氨酸/谷胱甘肽的比值也与死亡率显著相关（校正HR， 1.92; 95% CI, 1.39-2.64），且与高敏c反应蛋白水平无关，且与高敏c反应蛋白水平相关。在心血管死亡和合并死亡与心肌梗死的其他结局中也发现了类似的关联。血浆氨基硫醇、胱氨酸、谷胱甘肽及其比值量化的高氧化应激负荷与冠状动脉疾病患者的死亡率相关，这一发现独立于炎症负荷，并与炎症负荷相关。重要的是，这些数据支持非自由基生物学在驱动临床重要氧化应激中的新兴作用。
Supplemental Digital Content is available in the text. 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. 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. 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.