| Title: | Metabolite clusters linking fatty liver disease to cardiovascular mortality in coronary heart disease patients |
| Journal: | Nutrition Metabolism and Cardiovascular Diseases |
| Published: | 1 Dec 2025 |
| DOI: | https://doi.org/10.1016/j.numecd.2025.104535 |
| URL: | https://www.nmcd-journal.com/article/S0939-4753(25)00690-8/pdf |
Publication 17274
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Abstract
Background and aims We aimed to identify metabolite clusters and assess their relationships with prevalent steatotic liver disease (SLD) and fatal cardiovascular diseases (CVD) risk in coronary heart disease (CHD) patients. Methods and results We included 6127 CHD patients from the UK Biobank (UKB; discovery cohort) and 877 from the Alpha Omega Cohort (AOC; validation cohort). Metabolites were quantified at baseline (UKB: 2006-2010; AOC: 2002-2006) using the Nightingale Health 1H-NMR platform. We employed exploratory factor analysis to UKB metabolite data followed by confirmatory factor analysis in both cohorts. Prevalent SLD was defined as the upper sex-specific tertile of the Fatty Liver Index. Cause-specific mortality was monitored from baseline through 30th November 2022 for UKB and 31st December 2011 for AOC. Cox regression was used to derive prevalence ratios and hazard ratios with 95% confidence intervals for prevalent SLD and fatal CVD risk, respectively. Seven metabolite clusters emerged, mainly consisting of VLDL lipoproteins, LDL, small HDL, large HDL, very small VLDL, amino acids, and a cluster with docosahexaenoic acid, glycine, and glutamine. The small HDL cluster was inversely associated with prevalent SLD (PRUKB:0.80 [0.69, 0.92]; PRAOC:0.39 [0.07, 2.09]) and fatal CVD risk (HRUKB:0.76 [0.62, 0.93]; HRAOC:0.67 [0.15, 2.97]). The very small VLDL cluster was positively associated with prevalent SLD (PRUKB:1.44 [1.37, 1.51]; PRAOC:1.84 [1.57, 2.16]) and fatal CVD risk (HRUKB:1.10 [1.03, 1.17]; HRAOC:1.12 [0.91, 1.38]). Conclusion Small HDL and very small VLDL lipoproteins are likely involved in the biological pathways linking SLD to fatal CVD in CHD patients.</p>
4 Authors
- Luc Heerkens
- Gerard Bryan Gonzales
- Johanna M. Geleijnse
- Fränzel J.B. van Duijnhoven
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