Abstract
Background: The liver–heart axis potentially influences the risk of mortality in patients with heart failure. We aimed to identify the clinical utility of the fibrosis-4 (FIB-4) index in patients with heart failure for predicting mortality in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Patients with heart failure and a subsample of healthy participants were enrolled in the MyoVasc study (NCT04064450) and followed for nine years. Participants with excessive alcohol consumption were excluded. The Fatty Liver Index (FLI) and FIB-4 index were used to classify MASLD and hepatic fibrosis, respectively. Data were adjusted for potential confounders. The primary endpoint was all-cause mortality. Findings: 2726 participants, including 172 healthy individuals, were included in the study. The participants had a mean age of 64.4 ± 11.2 years and a median FIB-4 index of 1.59 (interquartile range [1.17; 2.17]). There were 532 deaths. The FIB-4 index was predictive for all-cause mortality (hazard ratio (HR) 1.341, 95% confidence interval (CI) [1.273; 1.412], p < 0.0001). The HRs and 95% CIs for the FIB-4 index in FLI categories were 1.597 [1.256; 2.031] (p = 0.00013, FLI <30), 1.802 [1.519; 2.138] (p < 0.0001, FLI 30–60), and 1.292 [1.215; 1.374] (p < 0.0001, FLI ≥60). The interaction term for the FIB-4 index with FLI ≥60 (reference FLI <30) was HR 0.774 [0.617; 0.972] (p = 0.027), indicating a smaller impact of the FIB-4 index in FLI ≥60 than in FLI <30 (HR 1.664 [1.333; 2.077], p < 0.0001). Multivariable linear regressions revealed relevant independent relationships between the FIB-4 index and N-terminal pro-B-type natriuretic peptide, systolic dysfunction, diastolic dysfunction and left ventricular hypertrophy in participants with a FLI below 60. Interpretation: In patients with heart failure, the FIB-4 index predicts all-cause mortality and relates to cardiac functional and structural changes, especially in those without MASLD. Funding: Johannes Gutenberg-University Mainz.
| Original language | English |
|---|---|
| Article number | 101153 |
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | The Lancet Regional Health - Europe |
| Volume | 48 |
| DOIs | |
| Publication status | Published - Jan 2025 |
Bibliographical note
Funding Information:This study was funded by the German Center for Cardiovascular Research (DZHK) and the Center for Translational Vascular Biology (CTVB) of the University Medical Center of the Johannes Gutenberg-University Mainz. J.B. receives funding from Colgate-Palmolive \u2013 Society of Toxicology, Onderzoeksraad Vrije Universiteit Brussel, and Chair Mireille Aerens for the Development of Alternative Methods. J.B. and J.M.S take part in the EASL mentorship programme.
Funding Information:
P.S.W reports outside the submitted work: consulting fees from Astra Zeneca, research grants from Bayer AG, research grants, consulting and lecturing fees from Bayer Health Care, lecturing fees from Bristol Myers Squibb, grants and consulting fees from Boehringer Ingelheim, grants, consulting and lecturing fees from Daiichi Sankyo Europe, consulting fees and non-financial support from Diasorin, non-financial support from I.E.M., grants and consulting fees from Novartis Pharma, lecturing fees from Pfizer Pharma, non-financial grants from Philips Medical Systems, and grants and consulting fees from Sanofi-Aventis.
Funding Information:
This study was funded by the German Center for Cardiovascular Research (DZHK) and the Center for Translational Vascular Biology (CTVB) of the University Medical Center of the Johannes Gutenberg-University Mainz. J.B. receives funding from Colgate-Palmolive\u2014Society of Toxicology, Onderzoeksraad Vrije Universiteit Brussel, and Chair Mireille Aerens for the Development of Alternative Methods. J.B. and J.M.S take part in the EASL mentorship programme. The authors thank all study participants and personnel of the MyoVasc study for their willingness to participate and support, respectively. P.S.W. is principal investigator of the German Center for Cardiovascular Research (DZHK), a principal investigator of the DIASyM research core (BMBF 16LW0241K), and principal inverstigator of the cluster for future curATime (BMBF 03ZU1202AA, 03ZU1202CD, 03ZU1202DB, 03ZU1202JC, 03ZU1202KB, 03ZU1202LB, 03ZU1202MB, 03ZU1202OA).
Publisher Copyright:
© 2024 The Author(s)