Mohammad Moman A, Noc Marco, Lang Irene, Holzer Michael, Clemmensen Peter, Jensen Ulf, Metzler Bernhard, Erlinge David
1 Department of Cardiology and Clinical Sciences, Skåne University Hospital, Lund University , Lund, Sweden .
2 Center for Intensive Internal Medicine, University Medical Center , Ljubliana, Slovenia .
Ther Hypothermia Temp Manag. 2017 Sep;7(3):152-161. doi: 10.1089/ther.2016.0041. Epub 2017 Mar 2.
Cardiovascular and inflammatory biomarkers in therapeutic hypothermia have been studied in cardiac arrest, but data on patients with ST-segment elevation myocardial infarction (STEMI) treated with therapeutic hypothermia are currently unavailable. A multiplex proximity extension assay allowed us to measure 157 cardiovascular disease (CVD) and inflammatory disease-related biomarkers in patients from the international, multicenter, and randomized trial; CHILL-myocardial infarction (MI) and to explore the associations of cardiovascular and inflammatory biomarkers. Blood samples were obtained from 119 patients with STEMI, randomized to hypothermia as adjunctive therapy to percutaneous coronary intervention (PCI) or standard care with PCI only. Blood samples were obtained at baseline (0 hour), 6, 24, and 96 hours post PCI, and stored at -80°C until they were analyzed by PROSEEK Multiplex CVD and PROSEEK Multiplex INF (Olink Bioscience, Uppsala, Sweden). Peak values from 6, 24, and 96 hours postrandomization were compared between treatment groups. One hundred fifty-seven cardiovascular and inflammatory biomarkers were evaluated. Peak values of four biomarkers (BDNF, DNER, CCL20, MMP3) were reduced in the hypothermia group as compared with the control group. In addition, seven markers were slightly elevated in the hypothermia group (OPG, FGF21, FS, IL12B, PRL, TIM, IL6). In a prespecified subgroup analysis of anterior infarctions, two additional markers were reduced (PTX3 and SELE). In this explorative proteomic study from the randomized trial CHILL-MI, four biomarkers were identified as having reduced peak plasma values in patients with STEMI treated with therapeutic hypothermia as adjunctive therapy to PCI as compared with patients treated with standard care of PCI. In addition, seven biomarkers were elevated in the group treated with hypothermia therapy. The effect of hypothermia on biomarker peak values was modest, possibly due to a low reduction in mean body temperature. Whether a faster and deeper cooling results in more pronounced effects is yet to be established.
治疗性低温中的心血管和炎症生物标志物已在心脏骤停患者中进行了研究，但目前尚无关于接受治疗性低温治疗的ST段抬高型心肌梗死（STEMI）患者的数据。一种多重邻近延伸分析方法使我们能够在一项国际多中心随机试验（CHILL-心肌梗死（MI））的患者中测量157种心血管疾病（CVD）和炎症性疾病相关生物标志物，并探索心血管和炎症生物标志物之间的关联。从119例STEMI患者中采集血样，这些患者被随机分为接受低温作为经皮冠状动脉介入治疗（PCI）辅助治疗组或仅接受PCI标准治疗组。在PCI术后基线（0小时）、6小时、24小时和96小时采集血样，并储存在-80°C直至通过PROSEEK Multiplex CVD和PROSEEK Multiplex INF（瑞典乌普萨拉Olink生物科学公司）进行分析。比较治疗组之间随机分组后6小时、24小时和96小时的峰值。评估了157种心血管和炎症生物标志物。与对照组相比，低温治疗组中四种生物标志物（脑源性神经营养因子（BDNF）、Delta/Notch样表皮生长因子相关受体（DNER）、C-C基序趋化因子配体20（CCL20）、基质金属蛋白酶3（MMP3））的峰值降低。此外，低温治疗组中有七种标志物略有升高（骨保护素（OPG）、成纤维细胞生长因子21（FGF21）、胎球蛋白A（FS）、白细胞介素12B（IL12B）、催乳素（PRL）、组织因子途径抑制物（TIM）、白细胞介素6（IL6））。在一项预先指定的前壁梗死亚组分析中，另外两种标志物降低（3型补体前体（PTX3）和E选择素（SELE））。在这项来自随机试验CHILL-MI的探索性蛋白质组学研究中，与接受PCI标准治疗的患者相比，在接受治疗性低温作为PCI辅助治疗的STEMI患者中，有四种生物标志物被确定血浆峰值降低。此外，低温治疗组中有七种生物标志物升高。低温对生物标志物峰值的影响较小，可能是由于平均体温降低幅度较小。更快、更深的降温是否会产生更显著的效果还有待确定。
