Abstract

A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle–brachial index (ABI) score (<0.9 or >1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610–0.756) to 0.715 (95% CI 0.645–0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687–0.770) to 0.752 (95% CI 0.771–0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.

摘要

一些研究检查了心肌梗塞 (MI) 和外周动脉疾病 (PAD) 即多部位动脉疾病 (MSAD) 患者的生物标志物。该研究的目的首先是，将生物标志物与 PAD/MSAD 的发生联系起来，其次，如果这些生物标志物除了临床特征外，还可以识别 MSAD 的 MI 患者。在两项前瞻性观察研究中，包括未选择的近期 MI 患者，PAD定义为踝臂指数（ABI）评分异常（<0.9 或 >1.4）。使用邻近延伸分析 (PEA) 技术，同时分析 92 种与心血管疾病相关的生物标志物。测试了生物标志物与 PAD 的单变量关联。随机森林用于识别与 PAD 具有较高关联的生物标志物。通过 c 统计分析了将生物标志物添加到临床特征的额外判别准确性。在 MI 后早期分析的主要患者队列中，九种生物标志物被确定为与 MSAD/PAD 显着相关。在预测分析中，确定了六种与 PAD 相关的生物标志物。其中三个；将肿瘤坏死因子受体 (TNFR-1)、肿瘤坏死因子受体 2 (TNFR-2) 和生长分化因子 15 (GDF-15) 添加到临床特征中时，c 统计量从 0.683 (95% CI 0.610–0.756) 提高到在主要患者队列中为 0.715（95% CI 0.645–0.784），结果相似，在次要患者队列中为 0.729（95% CI 0.687–0.770）至 0.752（95% CI 0.771–0.792）。与炎症通路相关的生物标志物与 MI 患者的 MSAD 相关。三个生物标志物 92；TNFR-1、TNFR-2 和 GDF-15，在此探索性补充信息中预测 MSAD 并强调进一步研究的重要性。