sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation

Eur J Clin Invest. 2015 Sep;45(9):899-905. doi: 10.1111/eci.12482. Epub 2015 Jul 14.

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.

Keywords: Soluble suppression of tumorigenicity-2; atrial fibrillation; biomarker; mortality.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • International Normalized Ratio
  • Longitudinal Studies
  • Male
  • Mortality
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, Cell Surface / blood*
  • Risk Factors
  • Stroke / etiology
  • Stroke / prevention & control*

Substances

  • Anticoagulants
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Receptors, Cell Surface