BMI tied to CV risk in ACPA-positive but not ACPA-negative RA patients: Study

Researchers have identified in a new study that body mass index (BMI) affects cardiovascular risk in rheumatoid arthritis (RA) patients differently based on their ACPA (anticitrullinated protein antibody) status and biologic therapy use. The results indicate that greater BMI is associated with decreased cardiovascular risk in ACPA-negative patients receiving biologics but is linked with increased cardiovascular risk in ACPA-positive patients, independent of biologic therapy. These findings underscore the intricate interconnection between immune activity, body composition, and cardiovascular events in patients with RA. The study was conducted by George A. K. and colleagues published in BMJ Rheumatic & Musculoskeletal Diseases.

Rheumatoid arthritis is a chronic autoimmune disorder that not just targets joints but also poses a greater risk of cardiovascular events like strokes and heart attacks. Obesity is usually regarded as a risk factor for heart disease, yet the contribution of BMI to cardiovascular events in RA is less well established, particularly in light of the effects of inflammation, immune factors such as ACPA, and biologic drug therapy.

This global observational study included data from 3,982 RA patients. The authors used two categories to assess cardiovascular outcomes:

  • Major Adverse Cardiovascular Events (MACE): such as myocardial infarction, stroke, or cardiovascular mortality

  • All cardiovascular events: including MACE, in addition to angina, revascularization procedures, transient ischemic attack (TIA), peripheral arterial disease, and heart failure

Multivariable Cox regression models stratified by center risk were used to assess how BMI, ACPA status, and biologic therapy individually and collectively impacted the risk of cardiovascular events.

Key Findings

  • Participants: 3,982 RA patients

  • MACE events: 192

  • Total cardiovascular events: 319

In ACPA-negative biologic users:

  • MACE risk decreased by 62% with increased BMI (HR = 0.38)

  • All cardiovascular event risk decreased by 33% (HR = 0.67)

In ACPA-positive patients (any biologic use):

  • MACE risk increased by 4% per BMI unit (HR = 1.04)

  • All cardiovascular event risk increased by 3% per BMI unit (HR = 1.03)

Three-way interaction significant:

  • MACE (p < 0.001)

  • All cardiovascular events (p = 0.028)

This research determines that the effect of BMI on cardiovascular risk in RA is not uniform. Increased BMI decreased cardiovascular risk in ACPA-negative patients on biologics, whereas increased BMI enhanced cardiovascular risk in ACPA-positive patients regardless of biologic therapy. These results emphasize the need for personalized RA treatment and prevention of cardiovascular disease according to the immune status of the patient and treatment approach.

Reference:

Karpouzas, G. A., Gonzalez-Gay, M. A., Corrales, A., Myasoedova, E., Rantapää-Dahlqvist, S., Sfikakis, P. P., Dessein, P., Hitchon, C., Pascual-Ramos, V., Contreras-Yáñez, I., Colunga-Pedraza, I. J., Galarza-Delgado, D. A., Azpiri-Lopez, J. R., Semb, A. G., van Riel, P. L. C. M., Misra, D. P., Patrick, D., Bridal Logstrup, B., Hauge, E.-M., … for An inTernationAl Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). (2025). Influence of body mass index on cardiovascular risk in rheumatoid arthritis varies across anti-citrullinated protein antibody status and biologic use. RMD Open, 11(2), e005464. https://doi.org/10.1136/rmdopen-2025-005464

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