6 Blood Biomarkers Identified to Predict CVD Risk in Patients With Rheumatoid Arthritis

Blood samples for testing | Image credit: Daniel CHETRONI – stock.adobe.com

Researchers have pinpointed 6 blood biomarkers linked to cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA).

These biomarkers, which were associated with significant change in target to background ratio, included baseline values of:

• Serum amyloid A
• C‐reactive protein
• Soluble tumor necrosis factor receptor 1
• Adiponectin
• YKL‐40
• Osteoprotegerin

Published in the Journal of the American Heart Association, the study was led by physicians at Mass General Brigham with specializations in CVD and rheumatology. According to the researchers, these 6 biomarkers can help predict a rise in arterial inflammation. Additionally, while these findings suggest the potential for clinical assessment of individual CVD risk, further research is necessary to ascertain their correlation with actual cardiovascular events like heart attacks or strokes.

“Each of the candidate biomarkers has substantial prior literature supporting a potential role in predicting cardiovascular events in patients with RA,” the researchers said. “If validated in an external RA cohort with good information about longitudinal cardiovascular events, these biomarkers may prove useful in developing a more accurate cardiovascular risk prediction score in RA.”

The TARGET trial assessed the impact of different RA treatment strategies on CVD risk by measuring changes in arterial inflammation using fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans conducted 24 weeks apart. Supported by prior research, a set of 24 candidate biomarkers was evaluated at baseline and week 24 follow-up. Longitudinal analyses investigated the relationship between baseline biomarker levels, measured in plasma EDTA, and changes in arterial inflammation target to background ratio.

The study included a total of 109 patients with RA, and this cohort was predominantly women with a median (IQR) age of 58 (53-65) years and median RA duration of 1.4 (0.5-6.6) years. None of the participants had recently used biologic disease-modifying anti-rheumatic drugs, with a median weekly methotrexate dosage of 20 mg, and 33% of participants used oral glucocorticoids. At baseline, 1.7% of participants had diabetes, 45.2% had hypertension, 20% had hyperlipidemia, and 12.2% were current tobacco users. The median body mass index was 29.3 kg/m², and individuals with known CVD were excluded from the study.

The researchers were also comparing the effects of 2 different drug combinations on arterial inflammation for patients with RA who did not respond well to methotrexate alone:

1. Either etanercept or adalimumab in combination with methotrexate
2. Triple therapy of methotrexate, sulfasalazine, and hydroxychloroquine

While both treatment strategies demonstrated significant decreases in target to background ratio with no difference observed between groups, baseline levels of certain biomarkers including serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-40, and osteoprotegerin were associated with notable changes in target to background ratio. According to the researchers, integrating these selected biomarkers with clinical variables improved the model fit, suggesting their potential utility in predicting cardiovascular risk in patients with RA.

“After identifying several biomarkers in the current analyses, we will attempt to replicate them in a large clinical cohort with longer follow‐up and clinical cardiovascular end points,” the authors said. “General population cardiovascular risk scores do not work well in RA, and prior attempts to improve them have either not included biomarkers or not conducted a broad search for candidate biomarkers. We look forward to attempts to replicate this work.”

Reference

Solomon DH, Demler O, Rist PM, et al. Biomarkers of cardiovascular risk in patients with rheumatoid arthritis: results from the TARGET trial. J Am Heart Assoc. 2024;13(5):e032095. doi:10.1161/JAHA.123.032095