ArticleJournal of the American Heart Association2026
Sarcopenia and Its Associated Metabolic Profile Predict Incident Heart Failure: A Prospective Cohort Study of 267 335 Adults in the UK Biobank.
Article in Journal of the American Heart Association, 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
backgroundSarcopenia is prevalent in heart failure (HF), but its role in incident HF and underlying metabolic mechanisms remains unclear. We examined the interplay between sarcopenia phenotypes, circulating metabolic profiles, and incident HF.
methodsWe analyzed UK Biobank participants without baseline HF. Associations between sarcopenia phenotypes and HF incidence were assessed using Cox regression. Nuclear magnetic resonance metabolomics was used to characterize sarcopenia-related profiles. Cox regression was applied to test metabolite-HF associations, and least absolute shrinkage and selection operator regression was further used to refine predictors. Incremental predictive value beyond clinical risk factors was evaluated using discrimination and reclassification metrics.
resultsDuring a median 15.3 years, 10 233 of 267 335 participants (mean age 56.5 ± 8.1 years; 44.6% men) developed HF. Groups with confirmed sarcopenia (n=1993) and low handgrip strength (normalized to body mass index) only (n=18 796) were associated with higher HF risk (hazard ratio [HR], 1.63 [95% CI, 1.44-1.85]; HR, 1.76 [95% CI, 1.66-1.85]) compared with the reference group, with stronger effects observed in younger adults and women. Metabolomic profiling revealed sarcopenia-related alterations (higher glycoprotein acetyls, glucose-lactate, phenylalanine, tyrosine, 3-hydroxybutyrate; lower omega-3 fatty acids, docosahexaenoic acid, glycine, glutamine, histidine), which also predicted higher HF risk (Bonferroni-adjusted
conclusionsSarcopenia, particularly reduced handgrip strength, was a strong predictor for incident HF. Lipid-, amino acid-, and energy metabolism-related alterations modestly improved risk prediction and partially mediated the association.
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