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.
| Original language | English (US) |
|---|---|
| Article number | e0157035 |
| Journal | PLoS One |
| Volume | 11 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Serum-based oxylipins are associated with outcomes in primary prevention implantable cardioverter defibrillator patients
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
PY - 2016/6/1
Y1 - 2016/6/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=84976291786&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0157035
DO - 10.1371/journal.pone.0157035
M3 - Article
C2 - 27281224
AN - SCOPUS:84976291786
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0157035
ER -