Cardiometabolic health-frailty phenotypes and bidirectional transitions between atrial fibrillation and heart failure: multistate trajectories and proteomic signatures.

Chuanyong Cui, Banghua Liu, Guangji Zhang, Zhongyan Du, Wenke Cheng

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Article in The journal of nutrition, health & aging, 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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5 authors.

Chuanyong CuiDepartment of Cardiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, China.

Banghua LiuDepartment of Cardiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, China.

Guangji ZhangZhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, 310053, China; School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Zhejiang Engineering Research Center for "Preventive Treatment" Smart Health of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Zhongyan DuZhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, 310053, China; School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Zhejiang Engineering Research Center for "Preventive Treatment" Smart Health of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address: duzhongyan@zcmu.edu.cn.

Wenke ChengDepartment of Cardiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, China; Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, 310053, China; School of Life Science, Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu 233030, China. Electronic address: Chengwenke@bbmu.edu.cn.

Funding

Wellcome Trust

6 · The paper itself

Abstract

objectiveTo examine whether a joint cardiometabolic health-frailty phenotype is associated with incident atrial fibrillation (AF), incident heart failure (HF) and progression to AF-HF comorbidity, and to identify candidate circulating protein signals related to this phenotype.

methodsAmong 319,048 UK Biobank participants without AF or HF, cardiometabolic status (healthy [CMH] or unhealthy [CMU]) and Frailty status (non-frail [NF] or pre-frail/frail [F]) defined four phenotypes. Cox and clock-forward multistate models estimated disease-specific and transition-specific hazards. Proteomic feature selection and exploratory mediation analyses included 28,206 participants with Olink plasma proteomic data.

resultsDuring follow-up, 17,844 participants developed AF, 5,410 developed HF, and 2,403 and 791 progressed from AF and HF, respectively, to comorbidity. Compared with CMH-NF, CMU-F was associated with the greatest risks of incident HF (hazard ratio (HR), 2.76; 95% confidence interval (CI), 2.59-2.95) and AF (HR, 1.49; 95% CI, 1.43-1.55). Corresponding multistate HRs were 2.98 (95% CI, 2.76-3.22) for baseline-to-HF, 1.45 (1.39-1.51) for baseline-to-AF, 1.76 (1.57-1.98) for AF-to-comorbidity, and 1.27 (1.02-1.57) for HF-to-comorbidity. Positive additive interactions indicated excess risk from coexisting cardiometabolic unhealthiness and frailty. Thirteen proteins showed statistical mediation signals for both outcomes; FABP4 yielded the largest positive mediated proportions (AF, 49.8%; HF, 32.9%) and transition-specific signals for baseline-to-AF and AF-to-comorbidity.

conclusionsCoexisting cardiometabolic unhealthiness and frailty identified individuals at greatest risk of AF, HF, and subsequent comorbidity. Exploratory proteomic analyses identified FABP4 as the most consistent preliminary signal, which warrants further validation in independent cohorts.

Indexed as

Atrial fibrillationCardiometabolic healthFrailtyHeart failureProteomics

Identifiers

PMID42858504

DOI10.1016/j.jnha.2026.101006

PMCPMC13677947

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.