LAP-defined hepatic steatosis and cardiometabolic risk in rheumatoid arthritis: a post-hoc analysis of the FRANCIS randomized trial.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with metabolic dysfunction-associated steatotic liver disease (MASLD), which may contribute to cardiovascular (CV) risk. This study aimed to examine the association between hepatic steatosis, measured by a non-invasive test, and CV risk markers in RA patients. This post-hoc analysis used cross-sectional and longitudinal data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), an open-label randomized controlled trial of intensive CV risk management in patients with rheumatoid arthritis without cardiovascular disease (CVD) or type 2 diabetes. Hepatic steatosis was assessed using the Lipid Accumulation Product (LAP) with sex-specific thresholds for rule-in and rule-out of severe steatosis. Associations between hepatic steatosis and carotid intima-media thickness (cIMT) were assessed using linear regression analysis. Crude associations were first evaluated in unadjusted models, followed by multivariable models adjusting for age, sex, BMI, and systolic blood pressure. Longitudinal changes in cIMT over 3 years were analyzed according to LAP-defined steatosis and treatment strategy. Among 236 RA patients (66% female; mean age 54 ± 10 years), those with LAP-defined steatosis had a more adverse cardiometabolic profile, including higher blood pressure, fasting glucose, and a more atherogenic lipid profile (all p < 0.05). Mean cIMT tended to be higher in the steatosis group (0.61 ± 0.10 vs. 0.57 ± 0.11 mm). In crude regression, LAP-defined steatosis showed a non-significant trend toward higher cIMT (B = 0.036, 95% CI - 0.003-0.076), which was no longer observed after multivariable adjustment (B = - 0.016, 95% CI - 0.050-0.019). Over 3 years, intensive treatment reduced cIMT progression compared with standard treatment in patients without LAP-defined steatosis (ΔcIMT 0.03 ± 0.07 vs. 0.06 ± 0.12 mm; p = 0.013), whereas no treatment effect was observed in patients with LAP-defined steatosis (ΔcIMT 0.05 ± 0.05 vs. 0.04 ± 0.05 mm; p = 0.696). Intensive treatment also produced greater improvements in lipid parameters, including reductions in total cholesterol and apoB in both groups, and increased apoAI mainly in participants with LAP-defined steatosis, while glycemic, hepatic, and inflammatory markers remained largely unchanged. In this exploratory post-hoc analysis, LAP-defined hepatic steatosis identified RA patients with a more adverse cardiometabolic profile. An unadjusted association with subclinical vascular burden was observed but was attenuated after adjustment for established CV risk factors. Intensive CV risk management was associated with lower cIMT progression in patients without LAP-defined steatosis, while no clear vascular effect was observed in those with LAP-defined steatosis. No evidence of differential treatment effects according to LAP-defined steatosis was found.