High plasma levels of soluble LOX-1 portends poor survival in acute coronary syndromes beyond GRACE 2.0: a multicentre prospective cohort study

Abstract

Abstract Background While inflammatory states and dyslipidemias confer a dismal prognosis following myocardial ischaemia, the role of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) which sits at the confluence of these conditions remains elusive. Given soluble LOX-1' (sLOX-1) pivotal role in inflammatory processes underlying atherosclerotic plaque progression, we sought to study its prognostic utility on the risk of adverse events in acute coronary syndromes (ACS). Purpose Hence, we aimed to investigate whether sLOX-1 is an independent predictor of all-cause death at one year beyond traditional and emerging risk factors for poor survival following ACS. Methods 2678 ACS patients were recruited in the prospective, multicentre SPUM-ACS trial, of which 2525 completed follow-up at one year. Major adverse cardiovascular events, including death from any cause, were adjudicated by an independent clinical endpoint committee. By employing high-sensitive enzyme-linked immunosorbent assay, sLOX-1 was assessed in the plasma at the time of presentation in ACS and age-matched chronic coronary syndrome (CCS) patients. Kaplan-Meier survival analysis and Cox proportional hazard regression models, adjusted for baseline variables and the GRACE 2.0 score, were used to study the predictive utility of sLOX-1. Results At the time of presentation, ACS patients, specifically those with ST-segment elevation ACS, had significantly elevated sLOX-1 levels as compared to patients with CCS (median, 35.40 vs. 2.00 pg/ml, P<0.0001). Patients in the upper sLOX-1 tertile were at heightened risk for both death from any cause (crude HR 1.785, 95% CI 1.083–2.941, P<0.05; adjusted HR 2.035, 95% CI 1.176–3.519, P<0.05) and CV death (crude HR 2.447, 95% CI 1.285–4.663, P<0.01; adjusted HR 2.383, 95% CI 1.206–4.710, P<0.05) compared to those in the first tertile. Importantly, sLOX-1 remained an independent predictor of all-cause death after adjustment for known risk factors of adverse outcome and the GRACE 2.0 score (adjusted + GRACE 2.0 HR 1.896, 95% CI 1.034–3.476, P<0.05). Conclusions Plasma sLOX-1 is elevated in ACS patients and predicts poor survival independent of both traditional and emerging risk factors and provides prognostic information beyond GRACE 2.0. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Swiss National Science FoundationFoundation for Cardiovascular Research - Zurich Heart House