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Prognostic value of circulating glypican-4 in chronic heart failure

Nora Schwegel1, Viktoria Höller1, Viktoria Santner1

  • 1Division of Cardiology, University Heart Center Graz, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Journal of Molecular Medicine (Berlin, Germany)
|April 7, 2026
PubMed

Insights

Glypican-4 (GPC-4) shows strong prognostic value for all-cause death in chronic heart failure patients, regardless of the underlying cause. This biomarker predicts survival but not heart failure-specific events.

Area of Science:

  • Cardiology
  • Biomarkers
  • Heart Failure Research

Background:

  • Glypican-4 (GPC-4) is an endothelial cell surface protein released during ischemia, inflammation, neurohumoral activity, and shear stress.
  • Its role as a prognostic marker in chronic heart failure requires further investigation.

Purpose of the Study:

  • To evaluate the prognostic significance of circulating GPC-4 levels in patients with chronic heart failure.
  • To assess GPC-4's predictive value in heart failure with reduced ejection fraction (HFrEF) and transthyretin amyloid cardiomyopathy (ATTR-CM).

Main Methods:

  • GPC-4 concentrations were measured in two prospective cohorts: HFrEF (n=205) and ATTR-CM (n=121).
  • Multivariable Cox regression analyses were performed, adjusting for key clinical variables.
  • Outcomes assessed included all-cause mortality, cardiovascular mortality, and worsening heart failure hospitalizations.

Main Results:

  • In HFrEF, GPC-4 independently predicted all-cause mortality (HR 1.69) and cardiovascular mortality (HR 1.61).
  • In ATTR-CM, GPC-4 independently predicted all-cause mortality (HR 1.96).
  • GPC-4 did not significantly predict worsening heart failure hospitalizations in either cohort.

Conclusions:

  • Circulating GPC-4 is a strong independent predictor of all-cause mortality in chronic heart failure across different etiologies.
  • GPC-4's prognostic value is demonstrated for overall survival but not for heart failure-specific outcomes.
  • Further research is warranted to fully elucidate GPC-4's role in cardiovascular disease.

Keywords:
Chronic heart failureGlypican-4Heart failure with reduced ejection fractionMortalityTransthyretin amyloid cardiomyopathy

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