Proteomic profiling identifies hepato-intestinal proteins as novel biomarkers for multi-organ injury and 1-year mortality in patients with acute myocardial infarction
Y Wang, M A Matter, P Westermann, A Sagmeister, S Costantino, F Paneni, B E Staehli, D Heg, L Raeber, B Gencer, N Rodondi, D Nanchen, F Ruschitzka, C B Messner, C M MatterAbstract
Background/Introduction
Acute myocardial infarction (AMI) triggers myocardial injury, systemic inflammation with potential fatal sequelae. The ischaemia burden may be associated with dysfunction of peripheral organs such as liver and intestine. Circulating proteins released from these organs may mirror patient risk.
Purpose
To investigate the association of early circulating hepato-intestinal proteins with heart failure (HF) and the risk of 1y-mortality in AMI patients.
Methods
From the SPUM-ACS cohort, 77 AMI patients who died within 1y follow-up (66 cardiovascular deaths) were matched 1:1 to event-free controls by age, sex, AMI subtype, symptom onset to percutaneous coronary intervention (PCI) time window, and recruiting site. Heparin plasma (collected <24h after symptom onset) was analyzed by Olink proteomic panels and mass spectrometry using a library-free workflow. Differential expression was assessed by moderated linear models (limma). Conditional logistic regression and unsupervised clustering were applied to proteins remaining changed after false discovery rate adjustment.
Results
24 proteins showed higher expression levels in patients who died than controls (Fig.1A). STRING analyses clustered them into three groups: acute inflammatory response, histones, and metabolic proteins mainly expressed in liver or intestine (Fig.1B). Pathway analysis revealed enrichment in growth factor signaling, cytokine regulation, and ethanol oxidation pathways. Differences of these metabolic proteins between cases and controls were more evident in patients who came with shorter symptom onset to PCI time (<6h) (Fig. 1C). After excluding proteins with less than 50% detection rate, FABP6 (fatty-acid binding protein 6), HAO1 (hydroxyacid oxidase 1), and LDHA (lactate dehydrogenase A) were identified to associate with risk of death after adjustment for renal function (eGFR, estimated glomerular filtration rate) (adjusted p=0.028; Fig.2A). Clustering using these hepato-intestinal proteins identified a subgroup with high expression of these proteins and Killip Class ≥2 (p<0.001, Fig.2B), indicating a close association between hepato-intestinal markers in blood and clinical signs of acute HF in AMI patients.
Conclusions
We identified a group of soluble hepato-intestinal proteins associated with clinical signs of HF and 1-year mortality in AMI patients. This study may provide novel insights into multi-organ damage and death risk in patients with AMI.