Study IDs 6 Blood Biomarkers for Predicting Cardiovascular Disease in Rheumatoid Arthritis

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A study from Brigham and Women's Hospital has identified 6 blood-based biomarkers that may predict cardiovascular disease risk in rheumatoid arthritis patients.

A new study suggests leveraging a group of 6 blood-based biomarkers could help predict future cardiovascular disease risk among people with rheumatoid arthritis.

An analysis of 24 potential biomarkers candidates tested among participants of the TARGET trial, results of the study indicate SAA, C-reactive protein, sTNFR1, adiponectin, YKL-40, and osteoprotegerin had a significant association with change in arterial inflammation target to background ratio among patients with rheumatoid arthritis.

“We think these biomarkers might improve our ability to predict risk and intervene early to help our patients,” said lead investigator Daniel H. Solomon, MD, MPH, chief of the Section of Clinical Sciences in the Division of Rheumatology and Matthew H. Liang Distinguished Chair at Brigham and Women’s Hospital.2 “The idea is that if we measure biomarkers that are specific to rheumatoid arthritis, we might be able to better identify those at highest risk of cardiovascular events.”

With mountains of data elucidating the risk of cardiovascular disease associated with rheumatoid arthritis and other diseases characterized by a marked increase in inflammation, research has shifted its focus to predicting and identifying patients with the greatest risk. With this in mind, Solomon and colleagues at sought to identify biomarkers with the potential to identify these changes in cardiovascular risk among patients with rheumatoid arthritis using a contemporary cohort with longitudinal data. Billed by investigators as the first study to examine a broad range of candidate biomarkers as predators of change in cardiovascular risk among a cohort of patients with rheumatoid arthritis, the study leveraged data from the Treatments Against RA and Effect on FDG PET/CT (TARGET) trial.1

Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, TARGET was a randomized controlled clinical trial comparing the effects of 2 treatment regimens on cardiovascular risk using [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) in patients with rheumatoid arthritis deemed inadequate responders to methotrexate. The treatment regimens used in the trial were triple therapy, with sulfasalazine, methotrexate, and hydroxychloroquine, and etanercept or adalimumab plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening.1

The primary analysis of the TARGET trial demonstrated both regimens were associated with significant reductions in total to background ratio (TBR) of the most diseased segment (MDS) at 6 months, with no difference between the 2 arms.1

In the current study, Solomon and colleagues sought to determine the relationship between baseline values of 24 candidate biomarkers and change in TBR MDS. Investors pointed out biomarker values were measured in plasma and model fit was assessed for the candidate biomarkers only, clinical variables only, and models combining both. Of the 159 patients enrolled in the TARGET trial, 109 were included in this study.1

The study cohort had a median age of 58.0 years, 71% were women, the mean duration of rheumatoid arthritis was 1.4 years, and the median baseline disease activity was considered moderate, as measured using DAS28-CRP 4.8.1

Based on the results of their initial analyses, investigators advanced SAA, C-reactive protein, sTNFR1, adiponectin, YKL-40, and osteoprotegerin to the multivariable models. IN these models, investigators found these were associated with a significant change in target to background ratio. Further analysis suggested these biomarkers, when added to the clinical variables, contributed to an adjusted R2 improvement from 0.20 to 0.33 (likelihood ratio P=.0005).1

“This is an important step towards using blood samples to measure changes in cardiovascular risk with the treatment of rheumatoid arthritis,” Solomon added.2


  1. 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. Published online February 28, 2024. doi:10.1161/JAHA.123.032095
  2. Mass General Brigham. Study Identifies Blood Biomarkers to Predict Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis. Mass General Brigham. February 28, 2024. Accessed February 28, 2024.