Fatty Liver Index and atherogenic risk determined by lipoprotein particle subclasses: A cross-sectional study of middle- to older-aged adults

Background and aims The Fatty Liver Index (FLI) provides a cost-effective way to screen for metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is associated with preclinical atherosclerosis, with cardiovascular disease (CVD) mortality being the leading cause of death among MASLD patients. Lipoprotein particles can provide better CVD risk prediction than traditional lipid measures. Yet, FLI associations with intermediate disease markers remain under-researched. This study addressed this gap by investigating FLI relationships with lipoprotein particle subclass concentrations. Methods This was a cross-sectional study of 1,713 middle-to older-aged men and women randomly selected from a large primary care centre. The FLI was calculated using triglyceride, body mass index, waist circumference and gamma-glutamyl transferase levels. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Linear regression analyses examined FLI associations with lipoprotein biomarkers. Results In fully adjusted models, higher FLI scores were associated with larger VLDL and smaller LDL and HDL particle size, more large and medium VLDL, small LDL, and less large HDL particle concentrations, and greater lipoprotein-related insulin resistance (all p<0.001). In models which examined these variable associations across FLI quintiles, significant dose-response relationships were observed ( p trend <0.001 for all). Conclusions These findings support the clinical utility of the FLI as a marker of atherogenic risk and as a tool for identifying at risk individuals. Incorporating the FLI into CVD risk assessment may help improve risk prediction in individuals with liver disease and guide targeted interventions.