RA, But Not Related Autoimmunity, Associated With Increased CV Risk

According to the study, rheumatoid arthritis (RA)-associated autoimmunity was not linked to increased cardiovascular (CV) event risk, suggesting systemic inflammation is likely required for precipitating CV events.

A study showed that rheumatoid arthritis (RA) was associated with increased cardiovascular (CV) event risk, but the association is with RA as a clinical chronic inflammatory disease and not with RA-associated autoimmunity.

The authors of the study, published in Arthritis Research & Therapy, explained that RA is already linked to increased CV mortality.

“CV events are particularly high in patients with RA‐specific autoimmunity, including rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA), raising the question whether RA‐specific autoimmunity itself is associated with CV events,” they said, which prompted their research.

The authors collected data from 20,625 patients included in the Electricité de France – Gaz de France cohort, which began in 1989 and includes annual updates. These data included new CV events such as CV-associated myocardial infarction, stroke, or death.

Of the 20,625 patients in the GAZEL cohort, most (72.8%) were men, and the mean (SD) age at inclusion was 44.2 (3) years in 1989. The authors used a piecewise exponential Poisson regression to evaluate the relationship between RA or RA-associated autoimmunity and risk of CV events.

Between 2005 and 2014, 1687 individuals presented with a new CV event—129 being lethal and 1558 being not lethal. A mean of 169 CV events occurred annually.

A questionnaire on rheumatic and musculoskeletal diseases (RMDs) was administered in 2010 and received 13,960 responses. Of these responses, 421 individuals said they had RA and 42 of these diagnoses were confirmed. The authors found no significant difference at baseline in 2005 between individuals with RA and the whole cohort.

The study found that confirmed RA was significantly associated with increased CV event incidence in both univariable and multivariable analyses (HR, 3.03; 95% CI, 1.13-8.11; P = .03). The data also showed that CV events were associated with older age, male sex, tobacco consumption, high blood pressure, dyslipidemia, and diabetes.

Plasma samples were available for 1618 patients in the whole cohort, allowing the authors to measure RF and ACPA in these individuals. Of this group, 178 demonstrated RF or ACPA without presence of RA. CV events were not associated with RF (HR, 1.15; 95% CI, 0.55-2.40, P = .70) or ACPA (HR, 1.52; 95% CI, 0.47-4.84, P = .48) without RA.

“The fact that ACPA and RF positivity precedes RA and that some individuals are positive for RF or ACPA without even developing the disease allows us to separately assess the role of RA-related autoimmunity and RA, as an inflammatory joint disease, on CV risk,” the authors said.

While noting their small sample sixe, the authors noted that RA-associated autoimmunity was not linked to increased CV risk, suggesting systemic inflammation is likely required for precipitating CV events.

“The fact that we found no significant association between RF and/or ACPA and CV events indicates, however, that there was no strong association between autoimmunity and CV risk, but does not formally allow to conclude to the absence of such association, considering the rather limited sample-size,” the authors said.


Gouze H, Aegerter P, Said-Nahal R, et al. Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events. Arthritis Res Ther. Published online February 24, 2022. doi:10.1186/s13075-022-02722-z

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