Identification of a specific inflammatory protein biosignature in coronary and peripheral blood associated with increased risk of future cardiovascular events

Background and rationale As an adjunct to coronary intervention, the Liquid Biopsy System (LBS, PlaqueTec, UK) enables accurate intracoronary blood sampling as previously documented. Here we investigate variation between local coronary and remote (peripheral) levels of certain proteins and how this might relate to cardiovascular risk assessment. Methods and Results Coronary artery blood samples were collected from 12 patients with obstructive coronary plaques before percutaneous coronary intervention (PCI), using the LBS. Peripheral blood samples were also collected, before and after PCI. Protein levels in coronary and peripheral plasma samples were analysed by proximity extension assay (PEA, Olink) and results were compared with blood samples from healthy controls and reference cohorts. Before PCI, 10/12 patients showed elevations in hepatocyte growth factor (HGF), pappalysin-1 (PAPPA) and spondin-1 (SPON1), in some cases >10-fold greater in coronary compared with peripheral samples. Following PCI, involving iatrogenic plaque rupture prior to stenting, peripheral levels of these proteins were elevated to a similar degree as coronary levels. In the other 2 patients, peripheral elevations for HGF, PAPPA and SPON1 (all >90th centile) were observed prior to PCI. This protein biosignature was absent in healthy controls but was detected in a minority of individuals in reference cohorts and associated with the occurrence of major adverse cardiovascular events (MACE) and mortality. Conclusions From investigation of coronary and peripheral blood samples, we identified a molecular signature, which when present in peripheral blood appears to portend worse outcomes. Measurement of these proteins could therefore aid identification of individuals at high risk of cardiovascular events.