Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• European heart journal, 2022-05, Vol.43 (19), p.1849-1860

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2022

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Aims 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). Methods and results 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). Conclusion 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. Clinical Trial Registration NCT01000701. Structured Graphical Abstract Structured Graphical Abstract Atherosclerotic plaques express high levels of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), with plaque regions particularly prone for instability showing accentuated LOX-1 abundance. The pro-inflammatory milieu within atherosclerotic plaques enhances LOX-1 synthesis, promotes LOX-1 shedding and thus soluble LOX-1 (sLOX-1) release. The turnover of membrane-bound LOX-1 determines plaque composition and thus stability, with systemically circulating sLOX-1 emerging as a novel biomarker reflecting plaque burden and vulnerability. In this multicentre prospective cohort study, we found that plasma levels of sLOX-1 are markedly elevated in patients presenting with acute coronary syndromes (ACS) when compared with both chronic coronary syndrome (CCS) and healthy subjects (CTRL). High sLOX-1 levels were independently associated with a higher multivariable-adjusted 1-year mortality risk following ACS, a finding that remained consistent after controlling for GRACE 2.0. In patients subjected to serial intravascular ultrasound following the index ACS, sLOX-1 dropped markedly in those with coronary plaque regression, while persistently high sLOX-1 levels were associated with plaque progression. §Adjusted for sex, age, ACS type, hs-CRP, history of hypercholesterolaemia, eGFR, LDL-C, and diagnosis of diabetes; †adjusted for sex, age, ACS type, hs-CRP, history of hypercholesterolaemia, eGFR, LDL-C, diagnosis of diabetes, NT-proBNP, and hs-TnT. ADAM, a disintegrin and metalloproteinase; GRACE, Global Registry of Acute Coronary Events; IVUS, intravascular ultrasound; MMP, matrix metalloproteinase; LOX-1, lectin-like oxidized low-density lipoprotein receptor-1; sLOX-1, soluble LOX-1.