Fibrosis-4 Index and Long-Term Cardiovascular Outcomes in Primary Aldosteronism

Background: The fibrosis-4 index (FIB-4) is a simple noninvasive marker originally developed to assess liver fibrosis risk. Accumulating evidence suggests that FIB-4 is associated with adverse cardiovascular outcomes, but its prognostic relevance in patients with primary aldosteronism (PA) remains unclear. Methods: In this retrospective multicenter cohort study, patients with PA were stratified into low, intermediate, and high FIB-4 groups using established cutoffs: <1.3, 1.3-2.67, and >2.67. Outcomes included all-cause mortality, ischemic stroke, hemorrhagic stroke, acute myocardial infarction, and major adverse cardiovascular events (MACE). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) across FIB-4 categories. Results: Among 2,467 patients with PA, 1,215 (49.3%) had FIB-4 <1.3, 863 (35.0%) had FIB-4 1.3-2.67, and 389 (15.8%) had FIB-4 >2.67. Patients with higher FIB-4 were older and had lower body mass index, worse renal function, lower potassium, and a higher comorbidity burden. During follow-up, all-cause mortality increased across FIB-4 categories, from 13.9% in the low FIB-4 group to 58.1% in the high FIB-4 group. After multivariable adjustment, FIB-4 >2.67 was associated with higher risks of all-cause mortality (adjusted HR, 1.98; 95% CI, 1.54-2.54) and MACE (adjusted HR, 1.78; 95% CI, 1.44?2.20), compared with FIB-4 <1.3. Adjusted linear regression analyses showed that higher FIB-4 was significantly associated with lower renin and higher aldosterone-to-renin ratio. Conclusions: In patients with PA, elevated FIB-4 identified a high-risk subgroup with increased all-cause mortality and MACE. FIB-4 may serve as a simple, noninvasive tool for prognostic stratification in patients with PA.