ApoJ-Glyc, an early marker of myocardial ischaemia, rapidly maps improved myocardial perfusion in STEMI patients undergoing successful primary PCI

Abstract Background Previous studies using experimental models and clinical retrospective samples have pointed to a potential role of glycosylated apolipoprotein J (ApoJ-Glyc) as a marker for the early detection of myocardial ischaemia. Ischaemia induces intracellular accumulation of non-glycosylated ApoJ that mirrors the reduction in ApoJ-Glyc serum levels in patients presenting with ST-segment elevation myocardial infarction (STEMI). Purpose The EDICA (Early Detection of Myocardial Ischaemia in Suspected Acute Coronary Syndromes by Apo J-Glyc as a Novel Pathologically based Ischaemia Biomarker) clinical trial assessed the performance of ApoJ-Glyc as a biomarker for the early detection of myocardial ischaemia in patients attending the A&E department with chest pain suggestive of acute coronary syndrome. Here, we report the observed changes in ApoJ-Glyc concentration in STEMI patients at baseline and after primary percutaneous coronary intervention (PPCI). Methods The EDICA trial, a multi-centre (10 sites), international, in vitro diagnostic study, assessed 404 patients attending the A&E department with suspected ACS. Of these, 291 patients had a final diagnosis of “non-ischaemic” event and 113 of “ischaemic” event. The main inclusion criterion was chest pain of suspected cardiac origin. Blood samples were obtained for the simultaneous assessment of high sensitivity-troponin and ApoJ-Glyc on admission (time 0) and at 1h and 3h thereafter. Two different glycosylated variants of ApoJ (ApoJ-GlycA2 and ApoJ-GlycA6) were analyzed with a novel ELISA in serum samples. Of the “ischaemic” patients, 33 had STEMI, of whom 85% underwent PPCI. Results As expected, in the presence of myocardial ischaemia, time 0 ApoJ-GlycA2 and ApoJ-GlycA6 serum levels decreased by 34% and 48%, respectively in STEMI patients, compared with non-ischaemic patients, i.e. ApoJ-GlycA2 in STEMI: 66 [52–95] μg/ml vs. non-ischaemic: 100 [72–131] μg/ml; P=0.0002; ApoJ-GlycA6 STEMI: 38 [34–67] vs. non-ischaemic: 73 [56–95] μg/ml; P<0.0001. ApoJ-GlycA6 showed a discriminating ability for the presence of STEMI with a 67% sensitivity and a 83% specificity (AUC=0.747, cut-off of 50μg/ml). In STEMI patients in whom PPCI successfully restored TIMI 3 flow, ApoJ-Glyc levels increased rapidly and significantly compared with time 0 levels (ApoJ-GlycA2: P=0.02 and P=0.003 for 1h and 3h; ApoJ-GlycA6: P=0.02 and P=0.002 for 1h and 3h) and compared to patients in whom PPCI was not performed (Table 1). Conclusions ApoJ-Glyc concentrations are reduced in STEMI patients on admission and increase rapidly after improved perfusion with PPCI, pointing to a potential role of this biomarker in the early detection of reversible ischaemia and the mapping of reversible changes. The mechanisms whereby ApoJ-Glyc levels rapidly and markedly increase after PPCI are speculative at present and deserve further investigation, together with the potential prognostic value of ApoJ-Glyc in this setting. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission 2020-EIC-SMEInstrument Phase 2; Spanish Ministry of Science, Innovation and Universities