Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes

• Published in: European heart journal Vol. 43; no. 19; p. 1849
• Main Authors: Kraler, Simon, Wenzl, Florian A, Georgiopoulos, Georgios, Obeid, Slayman, Liberale, Luca, von Eckardstein, Arnold, Muller, Olivier, Mach, François, Räber, Lorenz, Losdat, Sylvain, Schmiady, Martin O, Stellos, Konstantinos, Stamatelopoulos, Kimon, Camici, Giovanni G, Srdic, Annie, Paneni, Francesco, Akhmedov, Alexander, Lüscher, Thomas F
• Format: Journal Article
• Language: English
• Published: England 14.05.2022
• Subjects: Lipids; Inflammation; Acute coronary syndromes; LOX-1; Atherosclerosis
• ISSN: 1522-9645
• DOI: 10.1093/eurheartj/ehac143

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS). Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- and age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44-10.61; P = 0.0055] and 1-year intervals (T3: adjusted HR, 2.04; 95% CI, 1.19-3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: adjusted HR, 1.86; 95% CI, 1.04-3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: adjusted HR, 3.81; 95% CI, 1.62-19.62; P = 0.0036) and at 1 year (T3: adjusted HR, 2.29; 95% CI, 1.19-5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1: -4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59-0.86; P = 0.0031). Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD. NCT01000701.