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Objectives: To evaluate the relationship between soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and lipid levels in rheumatoid arthritis (RA) patients with and without carotid plaque (CP). Methods: Cross-sectional study nested of a RA cohort. RA patients without a previous cardiovascular event or statins' therapy, aged 40–75 years were recruited at an outpatient cardio-rheumatology clinic. Carotid ultrasound was performed in all study subjects. RA patients with CP were included and matched to RA patients without CP by age, gender, and traditional cardiovascular risk factors. Blood samples were drawn at the time of recruitment to measure sVCAM-1, sICAM-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid levels. Correlations between cell adhesion molecules, disease activity indexes, ESR and CRP with lipid levels were assessed with Spearman's correlation coefficient (rs). Results: We included 71 RA patients, 37 with CP and 34 without CP. RA (n = 71) patients had a moderate negative correlation of sVCAM-1 with total cholesterol (TC) (rs = − 0.366, p = 0.002) and low-density lipoprotein (LDL) (rs = − 0.316, p = 0.007), and a small negative correlation with high-density lipoprotein (rs = − 0.250, p = 0.036). ESR showed a small negative correlation with LDL (rs = − 0.247, p = 0.038). Patients with CP had a moderate negative correlation between sVCAM and TC (rs = − 0.405, p = 0.013). Patients without CP showed a moderate negative correlation between sVCAM with TC (rs = − 0.364, p = 0.034) and LDL (rs = − 0.352, p = 0.041), and sICAM with VLDL (rs = − 0.343, p = 0.047). Conclusions: RA patients showed an inverse association of sVCAM-1 and lipid levels. More studies are needed to define the precise role of sVCAM-1 in the lipid paradox of RA. Key Points • In RA patients with and without atherosclerosis, higher sVCAM-1 titers were associated with lower TC, LDL and HDL, and higher levels of ESR associated with lower LDL. • Higher levels of sVCAM-1 were associated with lower TC in RA patients with atherosclerosis, and with lower TC and LDL in RA patients without atherosclerosis. • There was an inverse association of sICAM-1 with VLDL, in RA patients without atherosclerosis. • sVCAM-1 may have a role in the detection of paradoxical lipid levels in RA, but more research is needed to validate our findings. [ABSTRACT FROM AUTHOR]