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Circulating microRNAs (miRNAs) and cytokines, such as growth differentiation factor-15 (GDF-15) and fibroblast growth factor-21 (FGF-21), may reflect the catabolic-anabolic imbalance and structural remodelling associated with this syndrome. To define the circulating signature of CHF by profiling muscle and remodelling-related miRNAs alongside GDF-15 and FGF-21, and to assess their associations with cardiac function and clinical phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-five CHF patients (median age 78.0 years, 40% male) and 10 controls (median age 56.8 years, 60% male) were studied. CC was defined as unintentional, non-oedematous weight loss \u22656% within 6 months. Circulating miRNAs were quantified by RT-qPCR, GDF-15 and FGF-21 by ELISA. CHF patients were classified as having reduced (HFrEF) or preserved ejection fraction (HFpEF). Associations with CC and clinical CHF phenotypes were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with controls, CHF patients showed lower levels of miR-15b, miR-29b, miR-133a, and miR-486 (all P &amp;lt; .01) and elevated GDF-15 levels (P &amp;lt; .001). FGF-21 was higher in patients with CC (P = .012), in HFrEF vs HFpEF (P = .039), and in NYHA III-IV vs I-II (P = .05). miR-29b levels were lower in CC (P = .019) and in HFrEF + CC vs HFpEF + nCC (P = .019). In CC, FGF-21 inversely correlated with miR-486 (\u03c1 = \u2212.69, P = .035), whereas GDF-15 inversely correlated with miR-21 (\u03c1 = \u2212.81, P = .007).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CHF is associated with miRNA suppression and elevated stress cytokine levels, amplified in CC. miR-29b and FGF-21 showed associations with CC, functional impairment, and structural remodelling, warranting validation in larger longitudinal cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eschf\/xvag229","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:55:14Z","timestamp":1791374114000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated miRNA-cytokine profiling reveals a molecular signature of cachexia in patients with chronic heart 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Translational and Precision Medicine, Sapienza University of Rome , Viale dell'Universit\u00e0 37, 00185 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8683","authenticated-orcid":false,"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) of German Heart Center Charit\u00e9, German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Molfino","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome , Viale dell'Universit\u00e0 37, 00185 Rome ,","place":["Italy"]},{"name":"Department of Interdisciplinary Studies on WellBeing, Health and Environmental Sustainability (BeSSA) , Sapienza University of Rome, Rieti 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