Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients. Methods Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated. Results Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m2), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups. Conclusions Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis. • RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis. • HCQ may provide a protective effect against liver fibrosis in RA patients. </entry> </row> </tbody> </tgroup> </Table>

Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk factors in rheumatoid arthritis

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2025年2月17日

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A. N. Saidi,
W. B. Theel,
B. Burggraaf,
A. J. van der Lelij,
D. E. Grobbee,
J. D. van Zeben,
E. van der Zwan-van Beek,
S. P. Rauh,
M. Castro Cabezas

摘要

Objectives

Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.

Methods

Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.

Results

Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m²), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.

Conclusions

Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies.

Key Points

• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.

• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.

• HCQ may provide a protective effect against liver fibrosis in RA patients.