Serum-Based Oxylipins Are Associated with Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients

PLoS One. 2016 Jun 9;11(6):e0157035. doi: 10.1371/journal.pone.0157035. eCollection 2016.

Abstract

Introduction: Individuals with systolic heart failure are at risk of ventricular arrhythmias and all-cause mortality. Little is known regarding the mechanisms underlying these events. We sought to better understand if oxylipins, a diverse class of lipid metabolites derived from the oxidation of polyunsaturated fatty acids, were associated with these outcomes in recipients of primary prevention implantable cardioverter defibrillators (ICDs).

Methods: Among 479 individuals from the PROSE-ICD study, baseline serum were analyzed and quantitatively profiled for 35 known biologically relevant oxylipin metabolites. Associations with ICD shocks for ventricular arrhythmias and all-cause mortality were evaluated using Cox proportional hazards models.

Results: Six oxylipins, 17,18-DiHETE (HR = 0.83, 95% CI 0.70 to 0.99 per SD change in oxylipin level), 19,20-DiHDPA (HR = 0.79, 95% CI 0.63 to 0.98), 5,6-DiHETrE (HR = 0.73, 95% CI 0.58 to 0.91), 8,9-DiHETrE (HR = 0.76, 95% CI 0.62 to 0.95), 9,10-DiHOME (HR = 0.81, 95% CI 0.65 to 1.00), and PGF1α (HR = 1.33, 95% CI 1.04 to 1.71) were associated with the risk of appropriate ICD shock after multivariate adjustment for clinical factors. Additionally, 4 oxylipin-to-precursor ratios, 15S-HEPE / FA (20:5-ω3), 17,18-DiHETE / FA (20:5-ω3), 19,20-DiHDPA / FA (20:5-ω3), and 5S-HEPE / FA (20:5-ω3) were positively associated with the risk of all-cause mortality.

Conclusion: In a prospective cohort of patients with primary prevention ICDs, we identified several novel oxylipin markers that were associated with appropriate shock and mortality using metabolic profiling techniques. These findings may provide new insight into the potential biologic pathways leading to adverse events in this patient population.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Arrhythmias, Cardiac / blood
  • Arrhythmias, Cardiac / diagnosis*
  • Arrhythmias, Cardiac / etiology
  • Biomarkers / blood*
  • Defibrillators, Implantable / adverse effects*
  • Female
  • Heart Failure / complications*
  • Heart Failure / therapy
  • Humans
  • Male
  • Middle Aged
  • Oxylipins / blood*
  • Predictive Value of Tests
  • Primary Prevention / instrumentation*
  • Primary Prevention / methods
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment

Substances

  • Biomarkers
  • Oxylipins