Rheumatoid Arthritis and Cardiovascular Disease Share Etiology

Researchers writing in Arthritis and Rheumatology report that high levels of anti-citrullinated protein antibodies (anti-CCP2) appear to be markers for future cardiovascular events in rheumatoid arthritis patients.

The study is based on an analysis of 2,814 rheumatoid arthritis patients who, over the course of 13 years, experienced 375 cardiovascular-related incidents, including acute coronary syndrome, stroke and cardiovascular-related deaths.

It is known that rheumatoid arthritis patients are at increased risk of cardiovascular disease due to a combination of traditional risk factors and, perhaps a shared etiology between rheumatoid arthritis and cardiovascular disease, wrote the authors who were led by Helga Westerlind, Ph.D., of the Karolinska Institute in Sweden. Previously, she and other researchers have reported that a correlation exists between accrued rheumatoid arthritis disease activity and high levels of anti-citrullinated protein antibodies (ACPA) and an increased risk of acute coronary syndromes, such as stroke, cardiovascular mortality, which was confirmed in this study.

In the new study, Dr. Westerlind and colleagues examined the presence and ‭levels o‬f anti-CCP2, specific ACPAs and their combinations, rheumatoid factor isotypes, and risk for acute coronary syndrome, stroke and cardiovascular-related death in this group of rheumatoid arthritis patients.

‭They found that elevated levels of anti-CCP2 were associated with acute coronary syndrome (1.46 hazard ratio (95% confidence interval), stroke (1.47 HR), cardiovascular-related death (P value 0.024) and major adverse cardiovascular events (MACE) (1.34 HR). Associations were also documented for ‭the num‬ber of ACPA sub-specificities; IgM rheumatoid factor with all cardiovascular endpoints except for acute coronary syndrome; and, IgA rheumatoid factor was found to be exclusively associated with cardiovascular disease-related death.

‭”From a clinical perspective, our data implies that patients with seronegative RA are at a lower risk of ‭CV eve‬nts, while patients with high anti-CCP2 levels or presence of IgA or IgG RF at diagnosis are at ‭higher ‬risk and might benefit from closer monitoring from a cardio preventative perspective. In this ‭regard,‬ specific ACPA sub-specificities offer no further predictive capacity.

‭”To con‬clude, in patients with RA, ACPA and rheumatoid factor are linked to risks for several types of CV endpoints, ‭and to C‬V and overall mortality, independently of smoking. These associations do not seem to be ‭driven ‬by any specific (pattern of) ACPAs, suggesting that for CV co-morbidity in RA, autoAb load ‭may be‬ more important than individual ACPAs. For RF the CV risks seem to vary across RF isotypes,” the authors wrote.

REFERENCE

Helga Westerlind,  Johan Rönnelid,  Monika Hansson,  Lars Alfredsson, et al. "Anti‐citrullinated protein antibody specificities, rheumatoid factor isotypes and incident cardiovascular events in patients with rheumatoid arthritis,"Arthritis and Rheumatology. First published:31 May 2020 https://doi.org/10.1002/art.41381