Longitudinal changes in fatty liver index, genetic susceptibility, and incident atrial fibrillation

Steatotic liver disease (SLD) may increase the risk of cardiovascular disease. However, few studies investigated such associations under dynamic changes in steatotic status. Thus, we aim to investigate the association between longitudinal changes in fatty liver index (FLI), a surrogate measure for assessing hepatic steatosis, and risk of incident atrial fibrillation (AF).

This study included 15,995 individuals from the UK Biobank whose hepatic steatosis status was assessed twice via the FLI in 2006-2010 and 2012-2013. We divided individuals into four groups: non-SLD (both FLI < 60), incident SLD (the first FLI < 60 and the second FLI ≥ 60), regressed SLD (the first FLI ≥ 60 and the second FLI < 60), and persistent SLD (both FLI ≥ 60). Multivariable Cox regressions, subgroup analyses by AF polygenic risk scores and mediation analysis to identify potential inflammatory mediators were performed.

Over a median follow-up of 4.4 years, 931 (5.8%) AF cases were documented. Compared to persistent SLD, SLD regressed was associated with a 31% lower risk of incident AF (HR: 0.69, 95%CI: 0.52-0.92). In the interaction analyses, the above association was strengthened in those with high genetic risk of AF (P for interaction = 0.013): compared with persistent SLD, for those with high genetic risk, regressed SLD and non-SLD significantly decreased AF risk (0.48, 0.31-0.74; 0.73, 0.54-0.97, respectively), but this was not the case for those with middle genetic risk (1.03, 0.62-1.69; 1.27, 0.89-1.82, respectively) and low genetic risk (0.78, 0.43-1.40; 0.88, 0.56-1.38, respectively). Additionally, in the mediation analyses, changes in the C-reactive protein-albumin-lymphocyte (CALLY) index served as potential mediators (ACME = 0.04, P = 0.04, proportion mediated = 8.5%).

In the middle-to-elderly aged population, FLI decrease may reduce AF risk, especially in individuals with high genetic risk. Moreover, this association was partially mediated by a change in the CALLY index.