Among 2,467 patients with primary aldosteronism (PA) tracked in a multicenter retrospective cohort, those with a Fibrosis-4 (FIB-4) index above 2.67 faced nearly double the all-cause mortality risk (adjusted HR 1.98; 95% CI 1.54–2.54) and a 78% higher risk of major adverse cardiovascular events compared to those with FIB-4 below 1.3. Mortality rates ranged starkly from 13.9% in the low FIB-4 group to 58.1% in the high FIB-4 group. Higher FIB-4 also correlated independently with lower renin activity and elevated aldosterone-to-renin ratios, hinting at a mechanistic link between systemic fibrosis burden and aldosterone-driven renin suppression.
PA affects roughly 5–10% of hypertensive patients and carries disproportionate cardiovascular risk beyond blood pressure elevation alone — driven by aldosterone's direct fibrotic and inflammatory effects on the heart and vasculature. Repurposing FIB-4, a cheap three-variable score (age, AST, ALT, platelet count), as a cardiovascular risk stratifier in PA is a genuinely pragmatic insight. It mirrors growing evidence that systemic fibrogenic signaling — not confined to the liver — underlies multiorgan cardiovascular risk.
Limitations are meaningful: the retrospective design precludes causal inference, confounding by age and comorbidity burden is significant even after adjustment, and the predominantly Asian cohort may limit generalizability. As a preprint not yet peer-reviewed, these findings require independent validation before influencing clinical practice. Still, if confirmed, routine FIB-4 scoring in PA patients could flag high-risk individuals warranting more aggressive intervention — an incremental but clinically actionable advance.
