Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Trial.
Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Trial.
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DOI：
10.1161/jaha.115.001886
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发表时间：
2015-05-20
影响因子：
5.4
通讯作者：
Mozaffarian D
中科院分区：
文献类型：
--
作者：
Wu JH;Marchioli R;Silletta MG;Masson S;Sellke FW;Libby P;Milne GL;Brown NJ;Lombardi F;Damiano RJ Jr;Marsala J;Rinaldi M;Domenech A;Simon C;Tavazzi L;Mozaffarian D
动物研究结果指出，氧化应激是引发术后房颤（PoAF）的关键机制，但氧化应激的特定生物标志物与人类PoAF风险相关的程度仍有待推测。我们评估了551例心脏手术患者血浆和尿液中经验证的脂肪酸衍生氧化应激生物标志物（F2-异前列烷、异呋喃和F3-异前列烷）与PoAF事件的相关性。在入组、手术结束和术后第2天测量生物标志物。持续≥30秒的PoAF通过心律条或心电图确认，并由中心裁定。评估结局直至出院或术后第10天，以先发生者为准。每种氧化应激生物标志物的尿液水平在手术结束时升高（超过基线2至3倍，P<0.001），随后在术后第2天下降至与基线相当的浓度。相反，血浆浓度在整个围手术期保持相对稳定。发生PoAF的受试者手术结束时的尿F2-异前列烷和异呋喃分别高出20%和50%（P≤0.009）。虽然基线生物标志物水平与PoAF无显著相关性，但手术结束和术后第2天异前列腺素和异呋喃类药物与PoAF呈相对线性相关。例如，手术结束时尿异呋喃和F3-异前列烷的极端四分位数多变量校正OR（95% CI）分别为1.95（1.05 - 3.62;趋势P =0.01）和2.10（1.04 - 2.25，趋势P =0.04）。生物标志物与PoAF的相关性在人口统计学、手术类型和药物使用方面差异很小（各P≥0.29）。这些新的结果增加了越来越多的证据，支持氧化应激升高在PoAF中可能的关键致病作用。URL：Clinicaltrials.gov唯一标识符：NCT 00970489。
Animal study results point to oxidative stress as a key mechanism triggering postoperative atrial fibrillation (PoAF), yet the extent to which specific biomarkers of oxidative stress might relate to PoAF risk in humans remains speculative. We assessed the association of validated, fatty acid–derived oxidative stress biomarkers (F2-isoprostanes, isofurans, and F3-isoprostanes) in plasma and urine, with incident PoAF among 551 cardiac surgery patients. Biomarkers were measured at enrollment, the end of surgery, and postoperative day 2. PoAF lasting ≥30 seconds was confirmed with rhythm strip or electrocardiography and centrally adjudicated. Outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Urine level of each oxidative stress biomarker rose at the end of surgery (2- to 3-fold over baseline, P<0.001) and subsequently declined to concentrations comparable to baseline by postoperative day 2. In contrast, plasma concentrations remained relatively stable throughout the perioperative course. Urine F2-isoprostanes and isofurans at the end of surgery were 20% and 50% higher in subjects who developed PoAF (P≤0.009). While baseline biomarker levels did not associate significantly with PoAF, end of surgery and postoperative day 2 isoprostanes and isofurans demonstrated relatively linear associations with PoAF. For example, the end of surgery extreme quartile multivariate adjusted OR (95% CI) for urine isofurans and F3-isoprostanes were 1.95 (1.05 to 3.62; P for trend=0.01) and 2.10 (1.04 to 2.25, P for trend=0.04), respectively. The associations of biomarkers with PoAF varied little by demographics, surgery type, and medication use (P≥0.29 for each). These novel results add to accumulating evidence supporting the likely key pathogenic role of elevated oxidative stress in PoAF. URL: Clinicaltrials.gov Unique identifier: NCT00970489.