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

  1. Cheng-Hsuan Tsai
  2. Yu-Ching Chang
  3. Chin-Chen Chang
  4. Wan-Chen Wu
  5. Yi-Yao Chang
  6. Uei-Lin Chen
  7. Bo-Ching Lee
  8. Chi-Sheng Hung
  9. Kuo-How Huang
  10. Jeff Shih-Chieh Chueh
  11. Vin-Cent Wu
  12. Yen-Hung Lin
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Abstract

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.

Novelty and Relevance

What Is New?

  • In this retrospective multicenter cohort of patients with primary aldosteronism, elevated FIB-4 identified a high-risk subgroup with increased all-cause mortality and MACE.

  • FIB-4 was associated with PA-related biochemical markers, including plasma renin activity and the aldosterone-to-renin ratio, suggesting a link between FIB-4 and renin suppression in PA.

  • This is the first study to evaluate the prognostic significance of FIB-4 in patients with PA and to examine its relationship with PA-related biochemical features.

What Is Relevant?

  • PA is clinically heterogeneous, and conventional biochemical markers may not fully capture the cumulative multisystem risk burden in high-risk patients.

  • FIB-4 is a simple, noninvasive, and routinely available index that may complement current risk stratification in PA by integrating biochemical, hepatic-metabolic, renal, and comorbidity-related information.

Clinical Implications?

  • Incorporating FIB-4 into PA assessment may help identify patients who warrant more comprehensive evaluation of cardiovascular, renal, hepatic, and metabolic risk.

  • Elevated FIB-4 may support closer clinical follow-up and more intensive risk-factor optimization in high-risk patients with PA.

Article activity feed

  1. Version published to 10.64898/2026.06.25.26356630 on medRxiv