Association between fatty liver index and cardiovascular-renal-metabolic syndrome risk: Nonlinear relationship based on NHANES 2011–2020 and mediating effect analysis of TyG, SII, and SIRI

The Fatty Liver Index (FLI) has been linked to several metabolic diseases, yet its relationship with cardiovascular-kidney-metabolic (CKM) syndrome remains uncertain. This cross-sectional study analyzed data obtained from the 2011-2020 National Health and Nutrition Examination Survey cycles. We employed multivariable-adjusted logistic regression models to examine the relationship between FLI and cardiovascular-kidney-metabolic (CKM) syndrome risk, complemented by comprehensive subgroup analyses. Restricted cubic spline (RCS) models with 3 knots were implemented to explore potential nonlinear associations between FLI and CKM syndrome. Furthermore, causal mediation analysis was conducted to assess the potential mediating roles of systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and triglyceride-glucose (TyG) index in the FLI-CKM syndrome association. In the fully adjusted model, a 1-unit increase in FLI was associated with an approximate 3% rise in CKM syndrome risk (adjusted odds ratio [OR] = 1.03, 95% confidence interval [CI]: 1.02-1.03, P < .001). Participants in the highest FLI quartile had an 18.1-fold higher risk of CKM syndrome compared to those in the lowest quartile (adjusted OR = 18.10, 95% CI: 11.70-27.90, P < .001). The RCS analysis confirmed a nonlinear relationship between FLI and CKM syndrome risk (P for non-linearity < .001, P for overall < .001). A threshold effect was identified, with 25.01 as the inflection point, after which the relationship between FLI and CKM syndrome risk leveled off. In addition, TyG, SII, and SIRI were identified as mediating factors between FLI and CKM prevalence, accounting for 18.82%, 0.77%, and 0.56% of the mediating proportions, respectively. The research findings emphasize the significant association between FLI and CKM prevalence, with TyG-related indicators playing a major mediating role.