Departments of Clinical Epidemiology, Biostatistics and Bio-informaticsAmsterdam UMC, location AMC Amsterdam The Netherlands.
Department of Vascular MedicineAmsterdam UMC, location AMC Amsterdam The Netherlands.
J Am Heart Assoc. 2021 Jan 19;10(2):e017120. doi: 10.1161/JAHA.120.017120. Epub 2021 Jan 14.
Background Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR-19b-1-5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio-cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR-19b-1-5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow-up time of 1.01±0.43 years. Low miR-19b-1-5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (-Log-miR-19b-1-5p, [unstandardized beta, 44.50; 95% CI, 2.20-86.80; <0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR-19b-1-5p expression was independently associated with a higher risk of MACCE (-Log-miR-19b-1-5p, [hazard ratio, 1.85; 95% CI, 1.23-2.80; <0.05]). Furthermore, a significant interaction was noted between the inverse miR-19b-1-5p expression and family history of premature coronary artery disease (=0.01) on the risk of MACCE. Conclusions Lower miR-19b-1-5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR-19b-1-5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.
由于对阿司匹林(aspirin resistance)无反应,急性冠状动脉综合征(acute coronary syndrome,ACS)患者发生复发事件的风险增加。体外血小板功能检测具有潜在局限性,使其不适合检测阿司匹林抵抗。我们研究了 miR-19b-1-5p 是否可作为 ACS 患者阿司匹林抵抗和未来主要不良心脑血管事件(major adverse cardio-cerebrovascular,MACCE)的生物标志物。
在这项队列研究中,我们于 2011 年至 2015 年期间,从基督城、香港、砂拉越和新加坡的多家三级医院招募了 ACS 患者。通过逆转录定量聚合酶链反应(reverse transcription quantitative polymerase chain reaction)测定 ACS 患者(n=945)的 buffy coat 中 miR-19b-1-5p 的表达。通过 Multiplate 聚集仪测定血小板功能。MACCE 在平均 1.01±0.43 年的随访期间收集。发现低 miR-19b-1-5p 表达与阿司匹林抵抗有关,这可以从阿司匹林存在下持续的血小板聚集观察到(-Log-miR-19b-1-5p,[未标准化β,44.50;95%置信区间,2.20-86.80;<0.05]),即使在调整了年龄、性别、种族和既往卒中史后也是如此。较低的 miR-19b-1-5p 表达与 MACCE 的风险增加独立相关(-Log-miR-19b-1-5p,[风险比,1.85;95%置信区间,1.23-2.80;<0.05])。此外,还注意到 miR-19b-1-5p 表达的倒数与早发冠心病家族史之间存在显著的交互作用(=0.01),这与 MACCE 的风险相关。
发现 miR-19b-1-5p 表达降低与阿司匹林治疗下的血小板持续聚集以及 ACS 患者的 MACCE 风险增加有关。因此,miR-19b-1-5p 可能是阿司匹林抵抗的合适标志物,并可能预测 ACS 患者 MACCE 的复发。