Disease activity in rheumatoid arthritis and the risk of cardiovascular events

Abstract

Objective: Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events.

Methods: We studied patients with RA whose cases were followed in a longitudinal US-based registry. Time-averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes.

Results: A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person-years (95% confidence interval [95% CI] 6.7-8.9). In models adjusted for variables noted above, a 10-point reduction in the time-averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13-29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable.

Conclusion: Our findings showed that reduced time-averaged disease activity in RA is associated with fewer CV events.

Figure 1

This figure shows the assembly of the study cohort from the CORRONA registry. DMARD, disease modifying anti-rheumatic drug.

Figure 2

This figure shows the hazard ratios for the primary analysis with the reference being high disease activity as measured by the Clinical Disease Activity Index. Model A is adjusted for age and gender only. Model B is adjusted for age, gender, age*gender interaction, and cardiovascular risk factors (prior MI, presence of CAD, diabetes, hypertension, hyperlipidemia, smoking, BMI (continuous), family history of MI, and aspirin use. Model C is adjusted for all variables in Model B + RA disease duration and baseline use of NSAIDs or selective COX-2 inhibitors, corticosteroids, disease modifying anti-rheumatic drugs, and biologic drugs.

Figure 3

This figure shows the hazard ratios for the subgroup analyses with the reference being high disease activity as measured by the Clinical Disease Activity Index. All hazard ratios are from Cox proportional hazard Model C which is adjusted for age, gender, age*gender interaction, and cardiovascular risk factors (prior MI, presence of CAD, diabetes, hypertension, hyperlipidemia, smoking, BMI (continuous), family history of MI, aspirin use, RA disease duration, and baseline use of NSAIDs or selective COX-2 inhibitors, corticosteroids, disease modifying anti-rheumatic drugs, and biologic drugs.