Metabolite clusters linking fatty liver disease to cardiovascular mortality in coronary heart disease patients.

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 November 30, 2022 for UKB and December 31, 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.