Higher Disease Activity in Early RA Predicts Increased Cardiovascular Disease Risk

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Serum-COMP was linked to an increased risk of both cardiovascular disease and coronary artery disease.

Baseline serum cartilage oligomeric matrix protein (COMP) may effectively predict the risk of developing cardiovascular disease (CVD) and coronary artery disease (CAD) in patients with early rheumatoid arthritis (RA), according to a study published in BMC Rheumatology.1 This risk was amplified in patients with active disease activity after 2 years post-diagnosis, as well as cumulative disease activity, which was independent of traditional CVD risk factors.

“In the recently updated European Alliance of Associations for Rheumatology (EULAR) recommendations, it is suggested that general population CVD risk algorithms should be adapted for patients with RA with an 1.5 multiplication factor for all patients,” wrote lead investigator Emil Rydell, MD, associated with the Rheumatology Department of Clinical Sciences at Lund University, Sweden, and colleagues. “This method estimates risk on a group level and does not take into consideration disease associated factors that influence risk among RA patients. There is a need for improved individual prediction of CVD in RA.”

COMP, an indicator of cartilage turnover, is found in both the synovial joints and arterial walls and is commonly more abundant in atherosclerotic plaques. The potential link between RA and CVD had yet not been analyzed, although previous research has showed an association between serum-COMP and joint damage progression.2

To investigate whether COMP, patient characteristics, CVD risk factors, and disease activity predict CVD in this patient population, a total of 233 patients with early RA were recruited from the rheumatology outpatient clinic of Skåne University Hospital Malmö in Sweden. After a baseline evaluation, subjects received follow-up appointments at 6 months, 1 year, and 2 years in which blood samples were analyzed and disease activity was monitored. Disability was determined via the Swedish Health Assessment Questionnaire (HAQ).

Data including height, weight, smoking status, other traditional CVD risk factors, and the time from symptom onset to the initiation of disease-modifying antirheumatic drug (DMARD) treatment were collected. The primary outcome was the first diagnosis of CVD during the follow-up period, while secondary endpoints included the first diagnosis of each CVD subcategory: CAD, cerebrovascular disease, or peripheral artery disease.

During the follow-up period, a CVD diagnosis occurred in 70 patients, while CAD was diagnosed in 52. Predictors of CVD and CAD included hypertension, diabetes, increased age, and male sex. Serum-COMP was linked to an increased risk of both CVD and CAD (crude hazard ratios [HRs] per SD 1.45; 95% confidence interval [CI] 1.17 – 1.80 and 1.51; 95% CI 1.18 – 1.92, respectively). However, when adjusted for hypertension, sex, age, erythrocyte sedimentation rate (ESR), and diabetes, results were comparable but not deemed significant (HRs 1.32, 95% CI .99 – 1.74 and 1.35, 95% CI .99 – 1.86).

The baseline disease activity was not shown to independently predict the diagnosis of CVD, although a Disease Activity Score-28 (DAS28) score of >5.1 at 2 years post-diagnosis was linked with subsequent CVD (adjusted HR 2.58; 95% CI 1.10 – 6.04) and CAD. Additionally, ESR and C-reactive protein (CRP), in addition to cumulative disease activity over a 2-year span were proven to be independent predictors of CVD and CAD.

Investigators noted the small sample size as a limitation of the study, as it affected the statistical power needed for the multivariate analysis. Further, subjects were included in the study prior to or shortly after biologic DMARD treatment initiation and were classified according to dated American College of Rheumatology (ACR) criteria. Therefore, results may not be reflective of patients diagnosed using more recent criteria and those treated using a treat-to-target strategy.

“Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA,” investigators concluded.


  1. Rydell E, Jacobsson LT, Saxne T, Turesson C. Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity. BMC Rheumatol. 2023;7(1):43. Published 2023 Dec 1. doi:10.1186/s41927-023-00367-2
  2. Forslind K, Eberhardt K, Jonsson A, Saxne T. Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis. Br J Rheumatol. 1992;31(9):593–8.