gms | German Medical Science

Introduction: Rheumatoid arthritis (RA) significantly increases the overall risk of cardiovascular disease (CVD). In addition to conventional risk factors, the inflammatory activity of the disease itself and medications that promote atherosclerosis contribute to an even greater risk. However, there is a lack of additional biomarkers for CVD risk assessment. In recent years, metabolomics has emerged as a valuable tool for identifying potential biomarkers in various diseases. In this study, we conducted metabolomics analysis in RA patients, both with and without disease-modifying antirheumatic drug initiation (DMARD) therapy.

Methods: Observational, cross-sectional investigation that included patients with established RA. DMARD therapy, if prescribed, consisted of methotrexate alone or in combination with other cDMARDs or bDMARDs or other cDMARDs or bDMARDs without MTX, respectively. Metabolomic profiling was conducted using a Bruker AVANCE NEO 600 MHz NMR spectrometer. The spectra obtained were Fourier transformed using TopSpin software (version 4.0, Bruker Biospin, Germany). All spectra were automatically phased and subjected to baseline correction. Subsequently, the spectra were analyzed using the proprietary Profiler software (version 1.4_Blood, lifespin GmbH, Germany) and a quantitative metabolite list was generated.

Results: In total, 47 patients with untreated and 153 individuals with DMARD-treated RA were included. In general, RA patients with arterial hypertension showed higher glucose and mannose levels than non-hypertensive subjects. Also, diabetics displayed significant differences between several intermediates (n=15) of the amino acid and lipid metabolism. Patients with a Framingham score of 20+ showed 19 distinct metabolic aberrations from individuals with a score of below 10. Finally, the following metabolites significantly differed between DMARD- and DMARD+ RA: 1,2-propanediol, glycerol, high density lipoprotein, and leucine.

Conclusion: Our findings have aided in the identification of potential surrogate markers for assessing the burden of cardiovascular disease in individuals with RA. Selected candidates may have the potential to enhance the accuracy of cardiovascular risk assessment in RA thus allowing for a more comprehensive evaluation.