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


CONCLUSIONS
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.
Department of Epidemiology, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
Yiyi
Y
Zhang
Department of Epidemiology, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
Eliseo
E
Guallar
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Elena
E
Blasco-Colmenares
Netherlands Metabolomics Centre, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
Amy C
AC
Harms
Netherlands Metabolomics Centre, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.|Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.|Discovery Sciences, Janssen R&D, Beerse, Belgium.
Rob J
RJ
Vreeken
Netherlands Metabolomics Centre, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.|Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
Thomas
T
Hankemeier
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Gordon F
GF
Tomaselli
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Alan
A
Cheng
D000368:Aged; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D015415:Biomarkers / Q000097:blood*; D017147:Defibrillators, Implantable / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D054883:Oxylipins / Q000097:blood*; D011237:Predictive Value of Tests; D011322:Primary Prevention / Q000295:instrumentation* / Q000379:methods; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment
D015415:Biomarkers; D054883:Oxylipins