Dregoesc Mihaela Ioana, Ţigu Adrian Bogdan, Bekkering Siroon, van der Heijden Charlotte D C C, Bolboacǎ Sorana Daniela, Joosten Leo A B, Visseren Frank L J, Netea Mihai G, Riksen Niels P, Iancu Adrian Corneliu
Department of Cardiology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Medfuture-The Research Center for Advanced Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Front Cardiovasc Med. 2022 Feb 8;9:731325. doi: 10.3389/fcvm.2022.731325. eCollection 2022.
Despite the advances in the control of traditional risk factors, coronary artery disease (CAD) remains the greatest cause of morbidity and mortality. Our aim was to establish the relation between plasma proteomics analysis and the risk of cardiovascular events in patients with stable CAD.
Patients with stable CAD and documented coronary atherosclerosis were screened for inclusion. Using proximity extension assays, 177 plasma proteins were simultaneously measured. The endpoint consisted of the first major adverse cardiovascular event (MACE) and was the composite of cardiovascular death, acute coronary syndrome, stroke, transient ischemic attack, or acute limb ischemia at 18 months follow-up. Cox proportional-hazards regression with adjustment for multiple comparisons was used to identify biomarkers for the outcomes of interest.
The cohort consisted of 229 patients. Six mediators were associated with MACE ( < 0.001). For these markers, the risk of MACE was calculated: tumor necrosis factor receptor superfamily member 13B (HR = 1.65; 95% CI: 1.30-2.10), C-C motif chemokine-3 (HR = 1.57; 95% CI: 1.23-1.98), decorin (HR = 1.65; 95% CI: 1.26-2.16), fibroblast growth factor-23 (HR = 1.56; 95% CI: 1.23-1.99), tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) (HR = 1.61; 95% CI: 1.23-2.11), and tumor necrosis factor receptor superfamily member 10A (HR = 1.69; 95% CI: 1.25-2.29). Except for TRAIL-R2, the other proteins were associated with MACE independent of age, sex, diabetes mellitus, or estimated glomerular filtration rate.
In patients with stable CAD, five novel biomarkers were identified as independent risk factors for adverse outcomes. Novel biomarkers could represent pharmacological targets for the prevention of adverse cardiovascular events.
尽管在传统危险因素控制方面取得了进展，但冠状动脉疾病（CAD）仍然是发病和死亡的主要原因。我们的目的是确定血浆蛋白质组学分析与稳定型CAD患者心血管事件风险之间的关系。
筛选出患有稳定型CAD且有冠状动脉粥样硬化记录的患者纳入研究。使用邻位延伸分析同时测量177种血浆蛋白。终点事件为首次主要不良心血管事件（MACE），是18个月随访时心血管死亡、急性冠状动脉综合征、中风、短暂性脑缺血发作或急性肢体缺血的综合结果。采用Cox比例风险回归并对多重比较进行校正，以确定与感兴趣结局相关的生物标志物。
该队列由229名患者组成。六种介质与MACE相关（<0.001）。对于这些标志物，计算了MACE风险：肿瘤坏死因子受体超家族成员13B（HR = 1.65；95%CI：1.30 - 2.10）、C - C基序趋化因子 - 3（HR = 1.57；95%CI：1.23 - 1.98）、核心蛋白聚糖（HR = 1.65；95%CI：1.26 - 2.16）、成纤维细胞生长因子 - 23（HR = 1.56；95%CI：1.23 - 1.99）、肿瘤坏死因子相关凋亡诱导配体受体2（TRAIL - R2）（HR = 1.61；95%CI：1.23 - 2.11）和肿瘤坏死因子受体超家族成员10A（HR = 1.69；95%CI：1.25 - 2.29）。除TRAIL - R2外，其他蛋白质与MACE的相关性独立于年龄、性别、糖尿病或估计肾小球滤过率。
在稳定型CAD患者中，五种新型生物标志物被确定为不良结局的独立危险因素。新型生物标志物可能代表预防不良心血管事件的药理学靶点。
