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Abstract <p>Glypican-4 (GPC-4), an endothelial cell surface protein, is released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. This study aimed to investigate the prognostic value of GPC-4 in chronic heart failure. GPC-4 concentrations were determined in two prospective cohorts: patients with chronic heart failure with reduced ejection fraction (HFrEF), and with transthyretin amyloid cardiomyopathy (ATTR-CM). Multivariable Cox regression analyses were adjusted for age, sex, estimated glomerular filtration rate, N-terminal B-type natriuretic peptide, and left ventricular ejection fraction. In HFrEF (<i>n</i> = 205, median age 66&#xa0;years, 22% women), 58 patients (28%) died, 18 (9%) from cardiovascular cause, and 46 patients (22%) were hospitalized for worsening heart failure (WHF) during 4.2&#xa0;years follow-up. In ATTR-CM (<i>n</i> = 121, median age 76&#xa0;years, 12% women), 34 patients (28%) died, 12 (10%) from cardiovascular cause, and 32 patients (26%) had a WHF hospitalization during 2.2&#xa0;years follow-up. Baseline GPC-4 (median [interquartile range]) levels were 1553 (1041, 1950) pg/ml in HFrEF, and 2071 (1579, 2893) pg/mL in ATTR-CM. In HFrEF, GPC-4 was independently associated with all-cause mortality (HR 1.69, 95%CI 1.22–2.32, <i>p</i> = 0.003) and cardiovascular mortality (HR 1.61, 95%CI 1.01–2.56, <i>p</i> = 0.045), but not with WHF hospitalizations. Conclusively, in ATTR-CM, GPC-4 independently predicted all-cause mortality (HR 1.96, 95%CI 1.12–3.44, <i>p</i> = 0.018), but not cardiovascular mortality and WHF hospitalizations. GPC-4 carries strong prognostic value for all-cause death in chronic heart failure across various etiologies, but not for heart-failure specific outcomes. Further studies are warranted to elucidate its value in cardiovascular disease.</p> Key messages <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Glypican-4 rises with ischemia, inflammation, neurohumoral activity, and shear stress.</p> </ItemContent> <ItemContent> <p>Circulating glypican-4 predicts prognosis in chronic heart failure, regardless of cause.</p> </ItemContent> <ItemContent> <p>Glypican-4 predicted all-cause death in heart failure with reduced ejection fraction and restrictive cardiomyopathy, but not heart failure–specific outcomes.</p> </ItemContent> </UnorderedList></p>

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Prognostic value of circulating glypican-4 in chronic heart failure

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月7日

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  • Nora Schwegel,
  • Viktoria Höller,
  • Viktoria Santner,
  • David Kajetan Zach,
  • Jakob Lugitsch,
  • Axel Muendlein,
  • Eva Maria Brandtner,
  • Andreas Leiherer,
  • Heinz Drexel,
  • Arthur Mader,
  • Andrea Borenich,
  • Stefan Pilz,
  • Martin Grübler,
  • Markus Wallner,
  • Klemens Ablasser,
  • Ewald Kolesnik,
  • Andreas Zirlik,
  • Dirk von Lewinski,
  • Nicolas Verheyen

摘要

Abstract

Glypican-4 (GPC-4), an endothelial cell surface protein, is released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. This study aimed to investigate the prognostic value of GPC-4 in chronic heart failure. GPC-4 concentrations were determined in two prospective cohorts: patients with chronic heart failure with reduced ejection fraction (HFrEF), and with transthyretin amyloid cardiomyopathy (ATTR-CM). Multivariable Cox regression analyses were adjusted for age, sex, estimated glomerular filtration rate, N-terminal B-type natriuretic peptide, and left ventricular ejection fraction. In HFrEF (n = 205, median age 66 years, 22% women), 58 patients (28%) died, 18 (9%) from cardiovascular cause, and 46 patients (22%) were hospitalized for worsening heart failure (WHF) during 4.2 years follow-up. In ATTR-CM (n = 121, median age 76 years, 12% women), 34 patients (28%) died, 12 (10%) from cardiovascular cause, and 32 patients (26%) had a WHF hospitalization during 2.2 years follow-up. Baseline GPC-4 (median [interquartile range]) levels were 1553 (1041, 1950) pg/ml in HFrEF, and 2071 (1579, 2893) pg/mL in ATTR-CM. In HFrEF, GPC-4 was independently associated with all-cause mortality (HR 1.69, 95%CI 1.22–2.32, p = 0.003) and cardiovascular mortality (HR 1.61, 95%CI 1.01–2.56, p = 0.045), but not with WHF hospitalizations. Conclusively, in ATTR-CM, GPC-4 independently predicted all-cause mortality (HR 1.96, 95%CI 1.12–3.44, p = 0.018), but not cardiovascular mortality and WHF hospitalizations. GPC-4 carries strong prognostic value for all-cause death in chronic heart failure across various etiologies, but not for heart-failure specific outcomes. Further studies are warranted to elucidate its value in cardiovascular disease.

Key messages

Glypican-4 rises with ischemia, inflammation, neurohumoral activity, and shear stress.

Circulating glypican-4 predicts prognosis in chronic heart failure, regardless of cause.

Glypican-4 predicted all-cause death in heart failure with reduced ejection fraction and restrictive cardiomyopathy, but not heart failure–specific outcomes.