# Association of the fibrosis-4 index with early-stage cardiovascular-kidney-metabolic syndrome in a longitudinal community-based cohort

## TL;DR

Higher liver injury measured by FIB-4 is linked to increased risk of cardiovascular-kidney-metabolic syndrome over time.

## Contribution

Demonstrates FIB-4 as an independent predictor of early-stage CKM syndrome in a longitudinal study.

## Key findings

- Each one-log-unit increase in FIB-4 was associated with increased odds of CKM syndrome at 1 and 3 years.
- The highest FIB-4 tertile showed significantly elevated risk compared to the lowest tertile across multiple time points.
- The association remained consistent after adjusting for demographics, lifestyle, and metabolic factors.

## Abstract

Cardiovascular-kidney-metabolic (CKM) syndrome, a systemic disorder affecting approximately 25% of U.S. adults, accounts for over 75% of healthcare costs. As a central metabolic regulator, the liver may play a pivotal role in the development of CKM. Although FIB-4, a non-invasive liver injury marker, correlates with cardiovascular disease, its value as an independent predictor of incident CKM syndrome remains unclear. We therefore investigated this association using baseline FIB-4 data.

We conducted a retrospective cohort study using data from the Health and Aging Trends Study in Anhui, China, including 1,633 adults aged ≥20 years. Baseline FIB-4 was log-transformed and analyzed continuously and in tertiles. Logistic regression models estimated odds ratios (ORs) for incident CKM syndrome at 1, 3, and 5 years, with sequential adjustment for demographics, lifestyle factors, comorbidities, and metabolic variables. Restricted cubic spline analysis explored non-linear associations. Missing data were addressed via multiple imputation.

Among 1,633 participants, 675, 798, and 910 developed CKM syndrome at 1, 3, and 5 years, respectively. Higher baseline FIB-4 was consistently associated with greater odds of incident CKM syndrome. In fully adjusted models, each one-log-unit increase in FIB-4 was associated with ORs of 1.32 (95% CI, 1.03–1.69) at 1 year, 1.31 (1.02–1.68) at 3 years, and showed a borderline association at 5 years (1.27, 0.99–1.63).Compared with the lowest tertile, the highest FIB-4 tertile showed significantly elevated risk: ORs of 1.50 (1.07–2.09), 1.75 (1.25–2.46), and 1.45 (1.03–2.05), with significant linear trends (P < 0.05). Subgroup analyses showed consistent associations with no significant interactions.

Elevated FIB-4 index was independently associated with a higher risk of incident CKM syndrome in a dose-dependent manner, suggesting liver injury may represent a potential target for early prevention.