Lin Hung-Ju, Chen Shu-Ting, Wu Hon-Yen, Hsu Hsiu-Ching, Chen Ming-Fong, Lee Yuan-Teh, Wu Kuen-Yuh, Chien Kuo-Liong
Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan.
Int J Cardiol. 2015 Mar 15;183:214-20. doi: 10.1016/j.ijcard.2015.01.043. Epub 2015 Jan 26.
Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke.
In this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F₂α (8-iso-PGF₂α), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine.
The levels of urinary 8-iso-PGF₂α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) μg/g creatinine versus 0.71 (1.34-3.02) μg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF₂α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF₂α, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers.
Our findings demonstrated that urinary 8-iso-PGF₂α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.
氧化应激和亚硝化应激被认为参与了心血管疾病的病理生理过程，但与中风发病风险的关系尚不清楚。
在这项巢式病例对照研究中，病例组由131名在筛查时无中风且在随访期间发生中风的参与者组成。对照组按年龄和性别进行1:1频率匹配。使用液相色谱-串联质谱法测量尿肌酐校正生物标志物的基线水平，包括8-异前列腺素F₂α（8-异-PGF₂α）、4-羟基壬烯醛与硫醚氨酸的结合物、8-羟基脱氧鸟苷和8-硝基鸟嘌呤。
中风病例组的尿8-异-PGF₂α水平高于对照组[中位数（四分位间距），1.13（2.23 - 4.36）μg/g肌酐对0.71（1.34 - 3.02）μg/g肌酐，p = 0.004]。调整心血管危险因素后，尿8-异-PGF₂α水平越高，中风发病风险越高的关联仍然存在[对数转换值每增加1个标准差，调整后的优势比为1.40；95%置信区间（CI），1.06 - 1.85；p = 0.005]，且在其四分位数间有显著增加趋势（趋势p值 = 0.016）。加入尿8-异-PGF₂α后，预测模型不仅提高了对有或无中风参与者的区分能力（综合判别改善，0.025；95% CI，0.006 - 0.045；p = 0.005），还增强了中风风险分层（净重新分类改善，19.8%；95% CI，4.6 - 35.1%；p = 0.011）。相比之下，其他三种生物标志物之间的关系不显著。
我们的研究结果表明，尿8-异-PGF₂α可能是预测中风发病风险的氧化应激独立生物标志物。
