Background/Purpose: The Fibrosis-4 index (FIB-4), a non-invasive tool for assessing liver fibrosis, has been linked to cardiovascular (CV) risk in the general population. This is due to the association of chronic liver diseases, particularly fibrosis or non-alcoholic fatty liver disease, with systemic inflammation, metabolic syndrome, and atherosclerosis. In this study, we calculated the FIB-4 index in patients with rheumatoid arthritis (RA), a condition associated with increased CV disease risk. We then examined its association with disease characteristics and CV comorbidities, including lipid profile, subclinical carotid atherosclerosis, and insulin resistance indices.

Methods: 465 RA patients underwent evaluations, including disease-related features, lipid profile, insulin resistance indices (using HOMA), metabolic syndrome criteria, and carotid ultrasound for intima-media thickness and carotid plaque detection. FIB-4 was calculated and categorized into low (< 1.45), indeterminate (1.45-3.25) and high risk ( >3.25) for fibrosis. A multivariable linear regression analysis was used to examine the associations between the disease characteristics and FIB-4.

Results: FIB-4 score had a median value of 0.95 (IQR 0.72-0.95). According to this score categories, 81% of patients had a low risk of fibrosis, while 18% and 1% had an indeterminate risk and high risk, respectively.Body mass index, obesity as BMI >30, and waist and hip circumferences, showed no significant association with FIB-4. SCORE2 CV risk calculator disclosed significant positive correlations with FIB-4 values (beta coef. 0.04, 95%CI 0.03-0.05, p< 0.001). Similarly, SCORE2 patients within moderate risk category showed higher FIB-4 values compared to those with low risk (beta coef. 0.3, 95%CI 0.2-0.4, p=< 0.001). Regarding classic CV risk factors, after multivariable analysis, while diabetes, dyslipidemia, and smoking did not demonstrate a significant association with FIB-4 scores, hypertension was associated with higher FIB-4 values. None of the lipid profile molecules demonstrated a significant association with FIB-4 scores. However, insulin resistance markers, including serum insulin, C-peptide levels, and HOMA2-IR index (beta coef. 0.04, 95%CI 0.009-0.06), p=0.009), showed significant positive correlations with FIB-4 values after adjustment for covariates. This was also the case for the presence of metabolic syndrome and statin use that were associated with significantly higher FIB-4 index levels. Relationship between RA disease data and subclinical carotid atherosclerosis with FIB-4 was adjusted for age, sex, waist to hip ratio, dyslipidemia, hypertension, triglycerides, apolipoprotein A1 and HOMA2-IR. The presence of carotid plaque and intima-media thickness were associated with higher FIB-4 values in univariable analysis. However, when adjusted for classic CV risk factors, this significance was lost. Acute phase reactants, the presence of rheumatoid factor or ACPA, and disease activity measured by several different scores did not demonstrate significant associations with FIB-4.

Conclusion: Up to 20% of RA patients show an abnormal FIB-4 index, which correlates with cardiovascular risk and insulin resistance.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-fibrosis-4-index-fib-4-correlates-with-cardiovascular-risk-and-insulin-resistance-in-patients-with-rheumatoid-arthritis/