Heart failure & cardiomyopathies

Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in Heart Failure with Preserved Ejection Fraction (HFpEF)

JACC Heart FailPublished Mechanistic study

Authors' conclusion

Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831.

Study context

Population
Patients with HFpEFcohorts n = 86, 216, 242
Comparison
Biomarker profiles associated with outcomes in observational HFpEF cohorts vs profiles of AZD4831 vs placebo in SATELLITE
Outcome
Biomarkers and pathways associated with clinical outcomes in HFpEF cohorts, and their change with AZD4831 vs placebo
Methodological detailssupervised principal component analyses, 3 independent observational cohorts, double-blind randomized 3-month trial (SATELLITE)
  • Supervised principal component analyses
  • 3 independent observational cohorts
  • Double-blind randomized 3-month trial (SATELLITE)

Main finding

As reported in the abstract

  • Top biomarkers associated with HF hospitalization or death: TNF-R1, TRAIL-R2, GDF15, U-PAR, ADM
  • Biomarkers associated with lower functional capacity and poorer quality of life: FABP4, HGF, RARRES2, CSTB, FGF23
  • AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2)
  • Top outcome-associated pathways (tumor microenvironments, wound healing signaling, cardiac hypertrophy signaling) predicted to be downregulated with AZD4831 vs placebo

Original publication

Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF. JACC Heart Fail. Published 3 May 2023. doi:10.1016/j.jchf.2023.03.002

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