Elevated sLOX-1 levels in ACS patients predict fatal events at 1 year
Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes
Introduction and methods
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is expressed by atherosclerotic plaques and has been suggested to play an important role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) [1-3]. Pro-inflammatory conditions in the atherosclerotic plaque simulate LOX-1 cleavage and in turn, its shedding product, soluble LOX-1 (sLOX-1) is emerging as a novel biomarker which reflects plaque burden and vulnerability [4,5]. Previous studies have shown that elevated sLOX-1 plasma levels are related to poor outcomes in stable patients during long-term follow-up [6,7].
Aim of the study
The objective of this study - known as the SPUM-ACS-study – was to study the relationship of sLOX-1 with mortality from any cause at 30 days and 1 year, the interplay of sLOX-1 with hs-CRP on risk of death from any or CV causes and the association of temporal changes of sLOX-1 with plaque progression in patients with ACS.
The SPUM-ACS study was an investigator-driven, multicentre prospective cohort study [8-11]. Between January 2010 and January 2019, a total of 2747 patients with ACS (n=2639) and chronic coronary syndrome (CCS; n=69) were included in the study as well as sex- and age-matched healthy controls (CTRL; n=120).
In a subcohort of ACS patients, longitudinal sLOX-1 measurements and serial intracoronary intravascular ultrasound (IVUS) at baseline and 1 year follow-up were performed.
- ACS patients displayed markedly elevated sLOX-1 levels compared to CCS patients and CTRL [CCS and CTRL vs ACS, 2.00 (IQR: 2.00–13.01) and 2.00 (2.00–6.93) vs. 35.08 (15.75-73.44) pg/mL, respectively, P<0.0001].
- sLOX-1 elevations were particularly evident in patients with ST-segment elevation myocardial infarction (STEMI).
- Plasma sLOX-1 showed weak to no correlation with hs-CRP, NT-proBNP, LDL-c and hs-TnT.
- High sLOX-1 levels (third tertile; T3) were associated with approx. threefold increased risk of death from any cause at 30 days (T3: fully adjusted HR, 3.11, 95% CI, 1.44–10.61; P=0.0055).
- High plasma sLOX-1 was a strong independent predictor of all-cause mortality over 1 year (T3: fully adjusted HR 2.04, 95% CI:1.19–3.92, P=0.0098), remaining consistent after adjusting the multivariable Cox model for the GRACE 2.0 score (T3: fully adjusted+GRACE 2.0 HR 1.86, 95%CI: 1.04–3.74, P=0.0391).
- High sLOX-1 showed a pronounced association with CV mortality at 30 days (T3: adjusted HR 3.81, 95%CI:1.62-19.62,P=0.0036) and at 1 year (T3: fully adjusted HR 2.29, 95%CI: 1.19-5.34, P=0.0148).
- Stratification according to hs-CRP and sLOX-1 showed that patient with high sLOX-1 had a consistently higher risk for death from any cause and death from CV causes.
- In the imaging substudy, a marked interaction could be established between plasma sLOX-1 trajectories and plaque dynamics in ACS patients receiving lipid-lowering therapy, and absolute changes in plasma sLOX-1 levels showed good discrimination for predicting plaque progression during the first year after ACS (AUC=0.74; 95% CI, 0.59–0.86; P=0.0031).
This study showed that sLOX-1 plasma levels are increased during ACS, particularly in patients with STEMI, predicting fatal events at 1 year beyond both traditional and established risk factors as well as GRACE 2.0. Persistently high plasma levels of sLOX-1 after ACS associate with coronary plaque progression in patients receiving lipid-lowering therapy. Thus, sLOX-1 has shown to be a novel and independent biomarker for fatal events in patients presenting with ACS.