Eyileten Ceren, Gasecka Aleksandra, Nowak Anna, Jarosz-Popek Joanna, Wolska Marta, Dizdarevic Al-Medina, Lang Irene M, Postula Marek, Ufnal Marcin, Siller-Matula Jolanta M
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.
1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
Thromb Res. 2022 May;213:195-202. doi: 10.1016/j.thromres.2022.03.025. Epub 2022 Apr 3.
Dual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs).
Our study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT.
We compared plasma concentrations of NO-related pathway metabolites in patients with ACS (n = 291) and investigated the prognostic value of SDMA as a bleeding predictor during 1-year follow-up. We measured the metabolites concentration using ultra performance liquid chromatography. Platelet reactivity was determined using impedance aggregometry.
Patients with the highest quartile (4th) of SDMA concentration had significantly lower platelet aggregation compared to those in the 1st-3rd quartiles of SDMA, based on ADP + PGE1-, AA-, and ADP-induced platelet reactivity tests (p = 0.0004, p = 0.002, p = 0.014, respectively). Patients with major or minor bleeding events had significantly higher concentrations of SDMA as compared to those without bleeding events or to those with minimal bleeding events (p = 0.019, p = 0.019, respectively).
Higher SDMA concentration is associated with lower platelet reactivity and is associated with major and minor bleeding events in patients with ACS on DAPT. Therefore, SDMA stands as a potential biomarker for individualization of duration and potency of antiplatelet therapies in the ACS population at high risk of bleeding complications.
双联抗血小板治疗(DAPT)可预防急性冠脉综合征(ACS)患者的缺血事件,但与出血事件风险增加相关。对称二甲基精氨酸(SDMA)是一氧化氮(NO)相关途径代谢物之一,是早期慢性肾脏病(CKD)和心血管疾病(CVD)的有前途的生物标志物。
我们的研究评估了 SDMA 在预测接受 DAPT 治疗的 ACS 患者出血事件中的作用。
我们比较了 ACS 患者(n=291)的 NO 相关途径代谢物血浆浓度,并在 1 年随访期间研究了 SDMA 作为出血预测因子的预后价值。我们使用超高效液相色谱法测量代谢物浓度。使用阻抗聚集法测定血小板反应性。
根据 ADP+PGE1-、AA-和 ADP 诱导的血小板反应性试验,SDMA 浓度最高四分位数(第 4 四分位数)的患者的血小板聚集明显低于 1-3 四分位数的患者(p=0.0004,p=0.002,p=0.014,分别)。与无出血事件或仅有轻微出血事件的患者相比,发生主要或次要出血事件的患者的 SDMA 浓度明显更高(p=0.019,p=0.019,分别)。
SDMA 浓度较高与血小板反应性降低相关,与接受 DAPT 的 ACS 患者的主要和次要出血事件相关。因此,SDMA 可能成为 ACS 人群中出血并发症风险高的个体化抗血小板治疗持续时间和强度的潜在生物标志物。