ArticleCirculation. Genomic and precision medicine2026
Metabolomic and Proteomic Signatures of Cardiorespiratory Fitness for Predicting All-Cause Mortality and Non-Communicable Disease Risk: A Prospective Study in the UK Biobank.
Article in Circulation. Genomic and precision medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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8 authors.
Funding
Abstract
backgroundCardiorespiratory fitness (CRF) is a strong predictor of mortality and noncommunicable disease risk, but its underlying molecular mechanisms are poorly understood. In this study, we identified 2 signatures of CRF (1 metabolomic and 1 proteomic) from UK Biobank participants who completed a risk-stratified submaximal cycle ergometer test, with CRF estimated from the heart rate response to incremental workload.
methodsThese signatures were validated in an independent sample of UK participants with data on metabolomics (n=354 222) and proteomics (n=29 961) to investigate prospective associations with all-cause mortality and noncommunicable diseases. Prospective associations were evaluated using Cox proportional hazards models adjusted for age, sex, ethnicity, socioeconomic status, lifestyle factors (including smoking, alcohol intake, diet, and body mass index), and relevant medical history.
resultsOur findings reveal that higher CRF is characterized by downregulation of pathways related to inflammation, triglyceride metabolism, glycolysis, and vascular dysfunction, and upregulation of pathways related to cholesterol transport, apolipoprotein particle size, and cytoskeletal remodeling. Leveraging these insights, we developed 2 novel signatures of CRF (1 metabolomic and 1 proteomic) that robustly reflect CRF levels (R
conclusionsTogether, these findings indicate that circulating metabolites and proteins are associated with CRF and with subsequent risk of mortality and noncommunicable diseases.
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