The Fibrosis-4 index predicts all-cause mortality in a cohort of patients at high cardiovascular risk partly through glomerular filtration rate reduction

Background and aim

Fibrosis-4 (FIB-4) index is a widely used test for non-invasively assessing liver fibrosis. We aimed to investigate the association between FIB-4 index and risk of all-cause mortality in patients at high cardiovascular (CV) risk and to determine whether coexisting renal dysfunction mediates this association.

Methods and results

Single-center prospective study of 994 patients with established or suspected coronary artery disease undergoing coronary angiography, followed for a median of 44 months. Mortality data were obtained through the Italian Health Card Database. At baseline, the median FIB-4 index was greater in deceased vs. alive patients (1.71 vs. 1.38, p < 0.001) and in those with reduced eGFR than in those with normal eGFR (1.65 vs. 1.37, p < 0.001). For each unit increase in the baseline log-FIB-4 index, the risk of all-cause mortality sharply increased during the follow-up (hazard ratio [HR] 2.31, 95%CI 1.31–4.08, p = 0.004). Similarly, assuming the lowest baseline FIB-4 risk category as the reference, the risk of all-cause mortality progressively increased across the indeterminate (HR 1.82, 95%CI 1.18–2.82, p = 0.007) and the highest baseline FIB-4 risk categories (HR 2.33, 95%CI 1.37–3.97; p = 0.002). A causal mediation analysis showed that about one-third of the effect of FIB-4 index on mortality risk was mediated by reduced eGFR (32.8 %, p = 0.01).

Conclusions

Increased FIB-4 index predicts the long-term risk of all-cause mortality in patients at high CV risk, and this risk is, at least in part, mediated by reduced eGFR. Further prospective studies are needed to confirm these findings.