Leucine-Rich α-2 Glycoprotein 1 Independently Predicts Adverse Clinical Events in Acute Coronary Syndrome

Aims: The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) is implicated in atherosclerotic cardiovascular pathogenesis. Herein, we examined the relationship between LRG1 and cardiovascular events in patients with acute coronary syndrome (ACS). <div> <br> </div> <div> Methods and Results: Proteomics technology was used to identify the plasma LRG1 in ACS and chronic coronary syndrome (CCS) patients and control patients prospectively recruited in a multi-center investigative study. Plasma LRG1 was accessed in the 3 groups with sex- and age-matched healthy subjects serving as additional controls (n = 1820). Compared with both CCS and controls, ACS patients showed markedly elevated LRG1 levels (p&lt;0.001) which were consistent in the Chui Yang Liu hospital (CYL) cohort (n=409) from another research center. Furthermore, among ACS patients, we evaluated the association of LRG1 with major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction, ischemic stroke, non-cardiovascular death, hospitalization for heart failure, recurrent angina pectoris and target vessel revascularization. After a median follow up of 1.23 (1.19-1.29) years, LRG1 was independently associated with increased MACE risk over 1 year (LRG1 tertile3 vs tertile1: HR: 4.35, 95% CI: 2.01-9.4, p=0.029) and 4-year (LRG1 tertile3 vs tertile1: HR:3.19, 95% CI 1.81-5.63, p&lt; 0.001) after adjust for clinical variables, biomarkers and Grace 2.0 score. The results were similar in the UK cohort. Mediation analyses indicated that CRP partially mediated the association of LRG1 with MACE, with the mediation proportion being 13.4% (95% CI: 4.2-28.1%) in the derivation cohort and 43.3% (95%CI:13.4-123.2%) in the UK validation cohort, respectively. Besides, LRG1 was correlated with thin-cap fibroatheroma (p=0.007) and plaque rupture (p=0.02) in the culprit lesion detected by optical coherence tomography. </div> <div> <br> </div> <div> Conclusion: LRG1 might be a novel and independent biomarker for cardiovascular events in patients presenting with ACS. LRG1 may provide prognostic information on the risk of recurrent cardiovascular events in the secondary prevention management of ACS and hold promise as a therapeutic target. </div>