Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients

Yiyi Zhang, Eliseo Guallar, Elena Blasco-Colmenares, Amy C. Harms, Rob J. Vreeken, Thomas Hankemeier, Gordon F. Tomaselli, Alan Cheng

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 PGF (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.

Original languageEnglish (US)
Article numbere0157035
JournalPLoS One
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

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Implantable cardioverter defibrillators
Oxylipins
oxylipins
Implantable Defibrillators
Primary Prevention
Serum
Shock
Mortality
arrhythmia
Metabolites
Cardiac Arrhythmias
metabolites
Systolic Heart Failure
metabolomics
heart failure
Unsaturated Fatty Acids
Proportional Hazards Models
polyunsaturated fatty acids
Hazards
oxidation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Zhang, Y., Guallar, E., Blasco-Colmenares, E., Harms, A. C., Vreeken, R. J., Hankemeier, T., ... Cheng, A. (2016). Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients. PLoS One, 11(6), [e0157035]. https://doi.org/10.1371/journal.pone.0157035

Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients. / Zhang, Yiyi; Guallar, Eliseo; Blasco-Colmenares, Elena; Harms, Amy C.; Vreeken, Rob J.; Hankemeier, Thomas; Tomaselli, Gordon F.; Cheng, Alan.

In: PLoS One, Vol. 11, No. 6, e0157035, 01.06.2016.

Research output: Contribution to journalArticle

Zhang, Y, Guallar, E, Blasco-Colmenares, E, Harms, AC, Vreeken, RJ, Hankemeier, T, Tomaselli, GF & Cheng, A 2016, 'Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients', PLoS One, vol. 11, no. 6, e0157035. https://doi.org/10.1371/journal.pone.0157035
Zhang Y, Guallar E, Blasco-Colmenares E, Harms AC, Vreeken RJ, Hankemeier T et al. Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients. PLoS One. 2016 Jun 1;11(6). e0157035. https://doi.org/10.1371/journal.pone.0157035
Zhang, Yiyi ; Guallar, Eliseo ; Blasco-Colmenares, Elena ; Harms, Amy C. ; Vreeken, Rob J. ; Hankemeier, Thomas ; Tomaselli, Gordon F. ; Cheng, Alan. / Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients. In: PLoS One. 2016 ; Vol. 11, No. 6.
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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.",
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AU - Zhang, Yiyi

AU - Guallar, Eliseo

AU - Blasco-Colmenares, Elena

AU - Harms, Amy C.

AU - Vreeken, Rob J.

AU - Hankemeier, Thomas

AU - Tomaselli, Gordon F.

AU - Cheng, Alan

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N2 - 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.

AB - 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.

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