ArticleFrontiers in cardiovascular medicine2026
Sex differences in leptin levels but not in the leptin response to sacubitril/valsartan in patients with heart failure with reduced ejection fraction.
Article in Frontiers in cardiovascular medicine, 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
Background: Leptin is an adipokine involved in metabolic regulation and neurohormonal activation and has been implicated in the pathophysiology of heart failure. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor, ARNI) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and may also influence metabolic pathways. However, it remains unclear whether ARNI therapy affects circulating leptin levels differently in men and women. Methods: In this observational study, patients with HFrEF from two clinical centres were evaluated before and after initiation of sacubitril/valsartan therapy. Serum leptin levels, N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), echocardiographic parameters and New York Heart Association (NYHA) class were assessed at baseline and follow-up. Sex-specific differences in leptin levels and leptin dynamics were analysed. Results: A total of 74 patients (20 women and 54 men) were included. Women exhibited significantly higher leptin levels compared with men at baseline (39.78 ± 31.95 vs. 10.39 ± 17.04 ng/mL, Conclusion: Women with HFrEF showed markedly higher circulating leptin levels than men at both baseline and follow-up. Leptin levels increased significantly in both sexes. However, there were no significant differences in absolute or relative leptin changes between women and men. Sex influences baseline leptin concentrations, but not the response to ARNI therapy. Further prospective studies are needed to clarify the mechanisms and clinical significance of leptin changes during sacubitril/valsartan treatment.
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