Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. The appearance of antibodies (Abs) against anti-oxLDL may be a pathogenic link between inflammation and atherosclerosis. An excessive CD40L/CD40 interaction is thought to play a pathogenic role in RA. The aim of this study was to search for the presence of subclinical atherosclerosis in a group of Venezuelan patients with RA and examine its correlation with anti-oxLDL Abs and serum levels of CD40L. 

Methods: Sixty-five RA patients and 26 healthy volunteers participated in the study. The presence and total serum levels of anti-oxLDL Abs and CD40L were examined by ELISA. The  biologically active CD40L was measured by an assay testing induction of nitric oxide production in vitro by RAW mouse 264.7 cells. The presence of subclinical atherosclerosis was detected by the measurement of intima-media-thickness (IMT) of the common carotid arteries using a Doppler ultrasound system (Esaote MyLab, 12 Mhz). Subclinical atherosclerosis was defined by an IMT ≥ 0.6 mm.  Statistical analysis was performed by Student´s t test and Chi-square and the Exact Fisher´s test for continuous and dichotomous variables, respectively. The study was approved by our hospital Ethics Committee and all patients signed an informed consent.

Results: We compared 65 RA patients (92.3% female; mean age 50,58±8,96) with 26 healthy controls (96.15% female; mean age 43.42±9.62). DMARDs and DMARDs plus biologics were received by 98.46% and 18.46% of patients, respectively. Mean disease duration was 7.32±6.04 years and mean and Disease Activity Score (DAS) 28-ESR was 3.19±1.5. Serum levels of anti-oxLDL were significantly higher in the RA patients than in healthy controls (34.48±9.83 vs. 24.74±6.4; P= 0,01). Serum levels of total CD40L and biologically active CD40L were also significantly higher in RA patients than in controls (9.13±2.74 vs. 3.86±1.21; P < 0,0001 and 3.81±1.94 vs. 1.6±1.11; P = 0,002). Patients with RA showed a higher proportion of an IMT ≥ 0.6 mm (P = 0,006). There was no correlation between serum levels of anti-oxLDL or CD40L with IMT.

Conclusion: To our knowledge this is the first study showing the presence of subclinical atherosclerosis in Hispanic patients with RA. Elevated serum titers of anti-oxLDL Abs and both total and soluble CD40L were features observed in this patient population suggesting their potential utility as biomarkers in this disease. Our preliminary results do not support a role for anti-oxLDL Abs or CD40L in the premature atherosclerosis observed in RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/subclinical-atherosclerosis-in-hispanic-patients-with-rheumatoid-arthritis-correlation-with-the-presence-of-anti-oxidized-ldl-antibodies-and-serum-levels-of-cd40l/