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Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

Linking liver fibrosis to cardiac structure, function, and heart disease: a community-based fibrosis-4 index study

  • Rongrong Yang1,2
  • Yubo Li3,4
  • Xingxu Yan3
  • Jiao Wang2,5,6
  • Min Zhu1
  • Sakura Sakakibara2
  • Abigail Dove2,7
  • Weili Xu2
7 affiliations
  1. 1Public Health Science and Engineering College, Tianjin University of Traditional Chinese Medicine
  2. 2Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet
  3. 3National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine
  4. 4Haihe Laboratory of Modern Chinese Medicine
  5. 5Center of Gerontology and Geriatrics, West China Hospital, Sichuan University
  6. 6National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University
  7. 7Department of Neurology, University of Pennsylvania Perelman School of Medicine
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Abstract

Background: The Fibrosis-4 Index (FIB-4) is a non-invasive tool used to assess advanced liver fibrosis. Although liver fibrosis has been linked to heart disease, its relationship with cardiac structure and function remains unclear.

Objectives: This study examined associations of FIB-4 with incident heart disease and cardiac morpho-functional phenotypes and explored whether cardiac phenotypes statistically accounted for part of the association.

Methods: In this prospective cohort study using the UK Biobank, 416,001 participants without known heart or liver disease at baseline (mean age 56.15 ± 8.09 years; 55.78% female) were followed for up to 17 years. FIB-4, calculated from age, AST, ALT, and platelet count, was analyzed continuously and using a high-risk threshold of >2.67. Incident coronary heart disease, cardiac arrhythmias (CA), and heart failure (HF) were identified from linked records. A subset of 33,927 participants underwent cardiovascular magnetic resonance (CMR) imaging a median of 10.20 years after baseline.

Results: Over a median follow-up of 14.61 years, 57,207 participants (13.75%) developed heart disease. Higher FIB-4 was associated with CA (HR = 1.32, 95% CI 1.24–1.41), HF (HR = 1.29, 95% CI 1.14–1.47), greater LV mass ( β =0.014, 95% CI 0.0003–0.027), chamber dilation, reduced atrial ejection fractions, and LV remodeling. Exploratory pathway analysis indicated that LA ejection fraction statistically accounted for 36.38% of the FIB-4–CA/HF association; causal mediation cannot be inferred.

Conclusion: Elevated FIB-4 was associated with incident CA and HF and with adverse CMR phenotypes. Exploratory pathway results were consistent with indirect pathways through cardiac remodeling, but the observational design and single CMR assessment preclude causal or temporal interpretation. FIB-4 may help identify people at higher cardiovascular risk.

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Cite

BibTeXRIS
BibTeX
@article{yang2026linking,
  title = {{Linking liver fibrosis to cardiac structure, function, and heart disease: a community-based fibrosis-4 index study}},
  author = {Rongrong Yang and Yubo Li and Xingxu Yan and Jiao Wang and Min Zhu and Sakura Sakakibara and Abigail Dove and Weili Xu},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1777872},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1777872/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Linking liver fibrosis to cardiac structure, function, and heart disease: a community-based fibrosis-4 index study
AU  - Rongrong Yang
AU  - Yubo Li
AU  - Xingxu Yan
AU  - Jiao Wang
AU  - Min Zhu
AU  - Sakura Sakakibara
AU  - Abigail Dove
AU  - Weili Xu
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.1777872
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1777872/full
AB  - Background: The Fibrosis-4 Index (FIB-4) is a non-invasive tool used to assess advanced liver fibrosis. Although liver fibrosis has been linked to heart disease, its relationship with cardiac structure and function remains unclear.  Objectives: This study examined associations of FIB-4 with incident heart disease and cardiac morpho-functional phenotypes and explored whether cardiac phenotypes statistically accounted for part of the association.  Methods: In this prospective cohort study using the UK Biobank, 416,001 participants without known heart or liver disease at baseline (mean age 56.15 ± 8.09 years; 55.78% female) were followed for up to 17 years. FIB-4, calculated from age, AST, ALT, and platelet count, was analyzed continuously and using a high-risk threshold of >2.67. Incident coronary heart disease, cardiac arrhythmias (CA), and heart failure (HF) were identified from linked records. A subset of 33,927 participants underwent cardiovascular magnetic resonance (CMR) imaging a median of 10.20 years after baseline.  Results: Over a median follow-up of 14.61 years, 57,207 participants (13.75%) developed heart disease. Higher FIB-4 was associated with CA (HR = 1.32, 95% CI 1.24–1.41), HF (HR = 1.29, 95% CI 1.14–1.47), greater LV mass ( β =0.014, 95% CI 0.0003–0.027), chamber dilation, reduced atrial ejection fractions, and LV remodeling. Exploratory pathway analysis indicated that LA ejection fraction statistically accounted for 36.38% of the FIB-4–CA/HF association; causal mediation cannot be inferred.  Conclusion: Elevated FIB-4 was associated with incident CA and HF and with adverse CMR phenotypes. Exploratory pathway results were consistent with indirect pathways through cardiac remodeling, but the observational design and single CMR assessment preclude causal or temporal interpretation. FIB-4 may help identify people at higher cardiovascular risk.
SN  - 2297-055X
ER  -