Proteomics in Hypothermia as Adjunctive Therapy in Patients with ST-Segment Elevation Myocardial Infarction: A CHILL-MI Substudy.

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.