title: sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrillation (AF) is associated with high morbidity and mortality, even despite the use of oral anticoagulation (OAC). Soluble suppression of tumorigenicity-2 (sST2) is a member of the interleukin-1 receptor family [interleukin-1 receptor-like 1 (IL1RL1)], which has been associated with an increased risk of mortality and morbidity in heart failure or acute coronary syndrome. We assessed the predictive value of sST2 levels in an unselected 'real-world' cohort of anticoagulated AF patients.
  
  
  METHODS
  We included 562 patients (49% male; median age 77 [IQR: 71-82]) with permanent AF who were stable (for at least 6 months) on OAC (INRs 2.0-3.0). sST2 levels were quantified by ELISA. Patients were followed-up for up to 4 years, and cardiovascular events and all-cause mortality were recorded.
  
  
  RESULTS
  Median (IQR) of sST2 levels was 51.23 (39.09-67.40) μg/L. Median follow-up was 1587 days [IQR 1482-1617], and during this period, 91 patients died (16.2%, 3.72%/year). The c-statistic for predicting mortality with sST2 was 0.58 + 0.03; P = 0.017). On multivariate analysis, age [hazard ratio (HR) 1.09 (1.05-1.13); P < 0.001], diabetes mellitus [1.76 (1.08-2.88); P = 0.023], previous stroke [2.16 (1.29-3.60); P = 0.003] and sST2 levels [1.008 (1.002-1.14); P = 0.008] were independently associated with mortality. Concentrations of sST2 were also significantly associated with the risk of mortality, even after adjusting for the CHA2 DS2 -VASc score [HR: 1.007 (1.001-1.013); P = 0.014].
  
  
  CONCLUSIONS
  In an anticoagulated AF patient's cohort, sST2 levels are an independent predictive factor of all-cause mortality. sST2 levels could be a biomarker used to improve clinical risk assessment in anticoagulated AF patients.
authors.affiliation: Departments of Cardiology and Clinical Analysis, Clinic University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma, Barcelona, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Vílchez
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma, Barcelona, Spain.|Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|IIB-Sant Pau Biomedical Research Institute, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pérez-Cuellar
authors.affiliation: Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|Department of Cardiology of Clinic University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
authors.affiliation: Hematology and Medical Oncology Unit, General University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gallego
authors.affiliation: Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|Department of Cardiology of Clinic University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Manzano-Fernández
authors.affiliation: Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|Department of Cardiology of Clinic University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
authors.affiliation: Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|Hematology and Medical Oncology Unit, General University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma, Barcelona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Noguera-Velasco
authors.affiliation: Department of Clinical Analysis, Clinic University Hospital Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.|Centre for Cardiovascular Sciences, University of Birmingham, City Hospital, Birmingham, UK.|Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma, Barcelona, Spain.|Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|IIB-Sant Pau Biomedical Research Institute, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordóñez-Llanos
authors.affiliation: Red de Investigación Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.|Hematology and Medical Oncology Unit, General University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D019934:International Normalized Ratio; D008137:Longitudinal Studies; D008297:Male; D009026:Mortality; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface
keywords: Soluble suppression of tumorigenicity-2; atrial fibrillation; biomarker; mortality