Time‐Varying Association of Rheumatoid Arthritis Disease Activity to Subsequent Cardiovascular Risk

Objective It is unknown how the relationship between disease activity in rheumatoid arthritis (RA) and cardiovascular (CV) events may change over time. We examined the potentially time‐varying association of RA disease activity to CV events. Methods We used the CorEvitas prevalent RA registry. The Clinical Disease Activity Index (CDAI) score category, averaged within each 6‐month window since enrollment, was the exposure, and the outcome was major adverse CV events (MACEs). We used marginal structural models to estimate the hazard ratio (HR), comparing each CDAI score category with remission, allowing for differential association over time. We predicted MACE‐free survival under several CDAI score scenarios. Results We found 44,816 eligible patients (77% female; mean age 58 years) with a crude event rate of 5.3/1000 person‐years (median follow‐up 3.4 years). The strongest association between higher CDAI score and MACEs was observed during the first 6 months of enrollment (HR for CDAI score low 2.29 [95% CI: 1.21‐4.36], moderate 2.81 [95% CI: 1.46‐5.43], and high 2.99 [95% CI: 1.48‐6.02]). These estimates gradually diminished; by year 5, the HRs were 1.00 (95% CI: 0.49‐2.05) for low, 1.18 (95% CI: 0.51‐2.71) for moderate, and 1.04 (95% CI: 0.45‐2.40) for high CDAI score. Predicted MACE‐free survival suggested a potential decrease in MACEs with a hypothetical earlier transition to remission. Conclusion The association of higher disease activity with CV events may be stronger earlier in the disease course of RA. Interventional studies may be warranted to precisely determine the effect of disease activity suppression on CV events in RA.