Association of Framingham Steatosis Index with the risk of all-cause, cardiovascular and cancer mortality: A prospective cohort study from NHANES

Aims The Framingham Steatosis Index (FSI) is a validated indicator for assessing non-alcoholic fatty liver disease. Previous studies have linked FSI to depression, chronic kidney disease, and cardiovascular diseases. However, evidence establishing its relationship with all-cause, cardiovascular, and cancer mortality remains limited. This study aims to clarify the associations between FSI and these mortality outcomes. Methods We conducted a prospective cohort study involving 15,006 adults with complete data from NHANES. The FSI, calculated from age, sex, body mass index, alanine aminotransferase, aspartate aminotransferase, hypertension, and diabetes status, was used to categorize participants into quartiles (Q1-Q4). Multivariate Cox proportional hazards models were employed to assess the associations of FSI with all-cause, cardiovascular, and cancer mortality. Results Over a median follow-up of 101.3 months, 1,698 all-cause deaths (11.3%), 427 cardiovascular deaths (2.8%), and 391 cancer deaths (2.6%) were recorded. After full multivariate adjustment, the highest FSI quartile (Q4) was associated with significantly increased risks compared to the lowest quartile (Q1): all-cause mortality (HR 2.40, 95% CI 1.98–2.90), cardiovascular mortality (HR 4.66, 95% CI 2.96–7.32), and cancer mortality (HR 2.19, 95% CI 1.51–3.18). Furthermore, FSI demonstrated curvilinear relationships with all mortality outcomes, with inflection points identified at -1.32 for all-cause mortality, -1.23 for cardiovascular mortality, and − 1.23 for cancer mortality. Conclusion In this U.S.-based cohort, a higher FSI demonstrated an independent and significant association with elevated risks of all-cause, cardiovascular, and cancer mortality. These findings underscore FSI as a potential prognostic marker for long-term health outcomes.