de Koning Marie-Sophie L Y, Al Ali Lawien, Bourgonje Arno R, Assa Solmaz, Pasch Andreas, van Goor Harry, Lipsic Erik, van der Harst Pim
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
Int J Cardiol. 2023 Nov 15;391:131214. doi: 10.1016/j.ijcard.2023.131214. Epub 2023 Jul 28.
Ischemia-reperfusion is accompanied by oxidative stress. Serum free thiols (FTs; sulfhydryl groups) reliably reflect systemic oxidative stress. This study evaluates longitudinal changes in FTs and their associations with outcomes after ST-segment elevation myocardial infarction (STEMI).
FTs were detected in archived serum samples from 378 participants of a neutral randomized trial on metformin therapy after STEMI. FT levels were determined at presentation with STEMI and at 24 h, 2 weeks, 4 months and 1 year thereafter. Outcomes included infarct size and left ventricular ejection fraction (LVEF), both determined with cardiac magnetic resonance imaging after 4 months, and 5-year major adverse cardiovascular events (MACE).
Serum FT concentrations at presentation and at 24 h were 356 ± 91 and 353 ± 76 μmol/L, respectively. The change in FTs between presentation and 24 h (ΔFTs) was associated with outcomes in age- and sex-adjusted analysis (per 100 μmol/L FT increase, β = -0.87 for infarct size, 95% confidence interval (CI): -1.75 to -0.001, P = 0.050; β = 1.31, 95% CI: 0.37 to 2.25 for LVEF, P = 0.007). Associations between ΔFTs and LVEF were markedly stronger in patients with Thrombolysis in Myocardial Infarction flow of 0 or 1 before percutaneous coronary intervention (PCI)(β = 2.73, 95% CI: 0.68 to 4.77, P = 0.009). Declining FTs during the first 24 h might be associated with higher incidence of 5-year MACE (P = 0.09).
Changes in oxidative stress early post-PCI may predict functional outcomes after STEMI. Our findings warrant validation in larger cohorts, and then may be used as rationale for development of thiol-targeted therapy in ischemic heart disease.
缺血再灌注伴随着氧化应激。血清游离硫醇（FTs；巯基）能可靠地反映全身氧化应激。本研究评估了ST段抬高型心肌梗死（STEMI）后FTs的纵向变化及其与预后的关系。
在一项关于STEMI后二甲双胍治疗的中性随机试验的378名参与者的存档血清样本中检测FTs。在STEMI发病时以及此后的24小时、2周、4个月和1年时测定FT水平。预后指标包括梗死面积和左心室射血分数（LVEF），两者均在4个月后通过心脏磁共振成像测定，以及5年主要不良心血管事件（MACE）。
发病时和24小时时的血清FT浓度分别为356±91和353±76μmol/L。在年龄和性别校正分析中，发病至24小时期间FTs的变化（ΔFTs）与预后相关（每增加100μmol/L FT，梗死面积的β=-0.87，95%置信区间（CI）：-1.75至-0.001，P=0.050；LVEF的β=1.31，95%CI：0.37至2.25，P=0.007）。在经皮冠状动脉介入治疗（PCI）前心肌梗死溶栓血流为0或1的患者中，ΔFTs与LVEF之间的关联明显更强（β=2.73，95%CI：0.68至4.77，P=0.009）。在最初24小时内FTs下降可能与5年MACE的发生率较高有关（P=0.09）。
PCI后早期氧化应激的变化可能预测STEMI后的功能预后。我们的研究结果需要在更大的队列中进行验证，然后可作为开发缺血性心脏病硫醇靶向治疗的理论依据。
