Relationship between metabolic dysfunction-associated steatotic liver disease and cardiovascular mortality risk in individuals with CKM stages 0-2: Mediating roles of inflammation and insulin resistance.
OBJECTIVE To examine the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with cardiovascular disease (CVD) mortality in adults with cardiovascular-kidney-metabolic (CKM) syndrome and to explore the possible roles of insulin resistance and inflammation. METHODS We analyzed 2009-2018 NHANES data including 10,061 adults with CKM staging (8340 at stages 0-2). MASLD was defined by the United States Fatty Liver Index (USFLI). We used restricted cubic spline models, Kaplan-Meier analysis, multivariable Cox regression, sensitivity analyses and mediation analysis to test the dose-response relationship, survival disparities and mediating effects. RESULTS MASLD prevalence rose with CKM stage progression. In CKM stages 0-2, USFLI scores linearly correlated with CVD mortality risk (P < 0.001). Participants with MASLD had poorer survival and a higher hazard of CVD mortality than those without MASLD (HR = 4.03, 95 % CI 1.55-10.48). Insulin resistance and inflammation partially mediated the observed association. CONCLUSIONS In early CKM syndrome, MASLD was associated with higher CVD mortality risk. Insulin resistance and inflammation may partly explain this association. These results support the potential value of integrating MASLD screening into early CKM syndrome risk stratification and management.