Thomas Andersen1, Thor Ueland2,3,4,5, Tatevik Ghukasyan Lakic6, Axel Åkerblom6,7, Maria Bertilsson6, Pål Aukrust2,3,4,5,8, Annika E Michelsen2,4, Stefan K James6,7, Richard C Becker9, Robert F Storey10, Lars Wallentin6,7, Agneta Siegbahn11, Frederic Kontny12,13. 1. From the Department of Anaesthesiology, Stavanger University Hospital, Norway (T.A.). 2. Research Institute of Internal Medicine, the National Hospital (T.U., P.A., A.E.M.), University of Oslo, Norway. 3. K.G. Jebsen Inflammatory Research Centre (T.U., P.A.), University of Oslo, Norway. 4. Faculty of Medicine (T.U., P.A., A.E.M), University of Oslo, Norway. 5. K.G. Jebsen - Thrombosis Research and Expertise Centre (TREC), University of Tromsø, Norway (T.U., P.A.). 6. Uppsala Clinical Research Centre (T.G.L., A.Å., M.B., S.K.J., L.W.), Uppsala University, Sweden. 7. Department of Medical Sciences, Cardiology (A.Å., S.K.J., L.W.), Uppsala University, Sweden. 8. Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway (P.A.). 9. Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, OH (R.C.B.). 10. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, United Kingdom (R.F.S.). 11. Department of Medical Sciences, Clinical Chemistry (A.S.), Uppsala University, Sweden. 12. Department of Cardiology, Stavanger University Hospital, Norway (F.K.). 13. Drammen Heart Centre, Norway (F.K.).
Abstract
OBJECTIVE: The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome. Approach and Results: Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes. CONCLUSIONS: In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
RCT Entities:
OBJECTIVE: The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome. Approach and Results: Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes. CONCLUSIONS: In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
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