Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes
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- Simon Kraler
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
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- Florian A Wenzl
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
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- Georgios Georgiopoulos
- Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne, UK
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- Slayman Obeid
- University Heart Center, Department of Cardiology, University Hospital , Zurich, Switzerland
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- Luca Liberale
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
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- Arnold von Eckardstein
- Institute of Clinical Chemistry, University Hospital of Zurich , Zurich, Switzerland
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- Olivier Muller
- Department of Cardiology, University Hospital of Lausanne, University of Lausanne , Lausanne, Switzerland
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- François Mach
- Cardiology, University Hospital Geneva , Geneva, Switzerland
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- Lorenz Räber
- Cardiology, Inselspital Bern , Bern, Switzerland
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- Sylvain Losdat
- CTU Bern, University of Bern , Bern, Switzerland
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- Martin O Schmiady
- University Heart Center, Department of Cardiac Surgery, University Hospital Zurich , Zurich, Switzerland
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- Konstantinos Stellos
- Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne, UK
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- Kimon Stamatelopoulos
- Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne, UK
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- Giovanni G Camici
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
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- Annie Srdic
- University Heart Center, Department of Cardiology, University Hospital , Zurich, Switzerland
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- Francesco Paneni
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
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- Alexander Akhmedov
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
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- Thomas F Lüscher
- Center for Molecular Cardiology, University of Zürich , Wagistrasse 12, 8952 Schlieren, Zurich, Switzerland
抄録
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Aims</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and results</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration</jats:title> <jats:p>NCT01000701.</jats:p> </jats:sec>
収録刊行物
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- European Heart Journal
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European Heart Journal 43 (19), 1849-1860, 2022-03-24
Oxford University Press (OUP)