ArticleJournal of molecular medicine (Berlin, Germany)2026
Prognostic value of circulating glypican-4 in chronic heart failure.
Article in Journal of molecular medicine (Berlin, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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