Impact of Sex and Age on Misclassification of Cardiovascular Risk in RA

Male doctor explaining results to middlea-ged female patient in hallway
Female sex and younger age are contributing factors to cardiovascular risk, yet many algorithms to predict cardiovascular disease do not give these much weight in their estimations.

In patients with rheumatoid arthritis (RA), younger age and female sex are potential contributing factors to underestimated cardiovascular (CV) risk, according to study results published in Arthritis Research & Therapy.

Studies have shown that patients with RA are at an increased risk for cardiovascular disease (CVD); however, the available algorithms to predict CVD, such as the Systematic Coronary Risk Evaluation Score (SCORE), underestimate the risk in this patient group.

The objective of the current study was to determine the contribution of age and sex to the misclassification of CV risk in patients with RA.

Investigators used data on CV risk factors and incident events from the Nijmegen early RA inception cohort, with a follow-up of 10 years or less. They used SCORE and the European Alliance of Associations for Rheumatology-modified SCORE algorithm for the prediction of CV risk.  The Hosmer-Lemeshow (H-L) test was utilized to check the concordance between the observed and predicted risk in subgroups according to sex and age.

The study included 863 patients with RA, including 128 patients (mean age, 61.2±10.2 years; 52% women) with a CV event recorded during follow-up, and 735 patients (mean age, 53.2±13.6 years; 68% women) with no history of CVD during the course of the study.

In the total cohort, there was a discrepancy between predicted and observed CV risk (H-L test P <.003) when the SCORE algorithm was used, especially in the subgroup of women (H-L test P <.001) rather than in the subgroup of men (H-L test P =.09).

Among women who developed CVD, more than a third (36%) had a low predicted CV risk (<10%). In contrast, only 10% of men who developed CVD had a low predicted CV risk, it was noted. The results were similar when the researchers applied a modified SCORE.

Patients aged 55 years or younger reported discrepancy between predicted and observed CV risk (H-L test P < .001), but older patients did not. The calculated underestimation of CV risk was highest in the youngest patients with RA (5.3% predicted vs 8% observed). Once again, the results were similar when the researches applied a modified SCORE.

The study had several limitations, including the relatively small sample size, inclusion of patients before implementation of CV risk management, and missing data on nonsteroidal anti-inflammatory drugs and corticosteroids

“[T]he results of our study suggest that the incidence of CVD among women and young RA patients initially assigned to the low-risk category is higher than predicted using current algorithms. Consequently, the CV risk in these subgroups seems underestimated,” concluded the researchers.


Rohrich DC, van de Wetering EHM, Rennings AJ, et al. Younger age and female gender are determinants of underestimated cardiovascular risk in rheumatoid arthritis patients: a prospective cohort study. Arthritis Res Ther. 2021;23(1):2.  doi:10.1186/s13075-020-02384-9