Abstract
IntroductionIndividuals 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).MethodsAmong 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.ResultsSix 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.ConclusionIn 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.
Highlights
Individuals with systolic heart failure are at risk of ventricular arrhythmias and all-cause mortality
17,18-DiHETE (HR = 0.83, 95% CI 0.70 to 0.99 per standard deviation (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 implantable cardioverterdefibrillator (ICD) shock after multivariate adjustment for clinical factors
We identified 6 oxylipins (17,18-DiHETE, 19,20-DiHDPA, 5,6-DiHETrE, 8,9-DiHETrE, 9,10-DiHOME and PGF1α) that were associated with the risk for appropriate ICD shocks in a prospective cohort of primary prevention ICD patients, suggesting a role as novel markers of ventricular arrhythmias
Summary
Among 479 individuals from the PROSE-ICD study, baseline serum were analyzed and quantitatively profiled for 35 known biologically relevant oxylipin metabolites. Among the 1,189 participants enrolled in the PROSE-ICD study, sufficient baseline blood sera for metabolic profiling of oxylipins were available in 479 subjects. This study was approved by the Johns Hopkins. Investigational Review Board (IRB) and all participants provided IRB-approved written informed consent. All participants underwent a comprehensive medical history, cardiovascular examination, and fasting blood collection [20]. Blood in nonanticoagulated tubes is centrifuged at 1500 rpm for 5 minutes. The serum is transferred into tubes containing 200 to 500 μL aliquots, frozen in liquid nitrogen and stored at −80°C
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