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Updated: May 16, 2025

Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
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Peroxiredoxin-4, a marker of systemic oxidative stress, is associated with incident heart failure.

Navin Suthahar1, Sanne G J Mourmans2, Anouk Achten2

  • 1Department of Cardiology, Erasmus MC, Cardiovascular Institute, Thorax Center, Rotterdam, The Netherlands.

European Journal of Heart Failure
|April 6, 2025
PubMed
Summary

Circulating peroxiredoxin-4 (Prx4) is a novel marker for systemic oxidative stress. Higher Prx4 levels are linked to an increased risk of developing heart failure (HF), including both preserved and reduced ejection fraction subtypes.

Keywords:
Antioxidant enzymeBiomarkerGeneral populationHeart failureOxidative stressPeroxiredoxin‐4

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Area of Science:

  • Cardiology
  • Biochemistry
  • Molecular Biology

Background:

  • Oxidative stress plays a key role in heart failure (HF) pathophysiology.
  • Direct measurement of reactive oxygen species is challenging due to their short half-lives.
  • Antioxidant enzymes like peroxiredoxins (Prx) are responsive to oxidative stress and can be quantified.

Purpose of the Study:

  • To investigate the association between circulating peroxiredoxin-4 (Prx4) and the incidence of heart failure (HF).
  • To determine if Prx4 levels predict HF risk across different subtypes (preserved and reduced ejection fraction).

Main Methods:

  • Utilized data from the Prevention of REnal and Vascular End-stage Disease (PREVEND) cohort.
  • Included 8199 participants with a median follow-up of 12.6 years.
  • Employed Cox proportional hazards models, adjusting for multiple cardiovascular risk factors.

Main Results:

  • A total of 349 HF events were recorded.
  • Elevated circulating Prx4 levels were significantly associated with an increased risk of incident HF (HR 1.22 per SD increase).
  • Prx4 independently predicted both HF with preserved ejection fraction and HF with reduced ejection fraction.

Conclusions:

  • Circulating Prx4 is a significant predictor of incident heart failure.
  • Prx4 associates with HF risk irrespective of ejection fraction status.
  • Further research is warranted to explore Prx4's utility as a real-time oxidative stress biomarker.