Hepatic Steatosis in Cardiovascular–Kidney–Metabolic Syndrome: Fatty Liver Index as a Predictor of Cardiovascular Outcomes

Cardiovascular-kidney-metabolic (CKM) syndrome describes the interplay between metabolic dysfunction, chronic kidney disease, and cardiovascular disease. While this framework advances our understanding of interrelated pathophysiology across multiple organ systems, further exploring the liver's role may be beneficial. The fatty liver index (FLI) is a cost-effective indicator of hepatic steatosis; however, its prognostic role in CKM syndrome remains unclear. This retrospective cohort study used data of 1,497,913 adults enrolled in the Korean National Health Insurance Database between 2009 and 2012. Participants were classified into four CKM syndrome stages (0/1, 2, 3, and 4) and further stratified by FLI (<60 vs. ≥60). The primary composite outcomes were all-cause death, heart failure, stroke, and myocardial infarction. Over an average follow-up of 12.60 ± 1.50 years, individuals with FLI ≥60 exhibited a 32% higher risk of the primary outcome (hazard ratio (HR) 1.324, 95% confidence interval (CI) 1.304-1.345, p < 0.001) compared to those with FLI <60. Each 1-standard deviation (SD) increment in the FLI (1-SD = 23.78) was associated with a 23% higher risk of the primary outcome. This dose-response relationship persisted across all CKM syndrome stages, with the most pronounced effect observed in earlier stages (0/1 and 2). A similar pattern was noted for the secondary outcomes. The FLI is an independent prognostic marker for cardiovascular outcomes across the CKM syndrome spectrum. Incorporating FLI into clinical practice could enhance early risk stratification and inform timely interventions, especially in patients at early stages of CKM syndrome, thereby potentially improving long-term cardiometabolic and renal outcomes.