AN ANALYSIS OF RISK FACTORS AND EFFECT OF TREATMENT ON THE DEVELOPMENT OF CARDIOVASCULAR DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Chronic inflammation has been associated with increased cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Tumor necrosis factor (TNF), a cytokine that mediates inflammatory processes, is elevated in patients with RA.Objectives: The objective of this study was to assess the impact of traditional CVD risk factors, RA disease severity, and effect of treatment on the development of CVD.Methods: Data from the CORRONA database through 11/15/2005 were analyzed. Cardiovascular events (coronary artery disease, myocardial infarction, congestive heart failure, or stroke) are denoted here by CVD. CVD event rates and incident rate ratios (IRR) were analyzed using mixed Poisson regression models. For estimated IRR, values >1.0 suggest increased risk and <1.0 suggest reduced risk. Covariates included measures of disease activity, patient demographics and behavior (eg, exercise), medication history, history of cardiovascular events, and history of diabetes. Stepwise regressions and best subset regressions were used to develop several 'best models' to predict CVD event rates as a function of TNF-antagonist use and relevant covariates.Results: Of data from 10,016 RA patients, 4837 were receiving TNF antagonists (5052 patient-years [pt-yrs] of exposure), including 2112 patients (2052 pt-yrs) receiving etanercept, 1070 (901 pt-yrs) receiving adalimumab, 2254 (2300 pt-yrs) receiving infliximab, and 5858 patients (4946 pt-yrs) who never received a TNF inhibitor. The number of CVD events was 75 (1.48 per 100 pt-yrs) among patients receiving TNF antagonists and 102 (2.06 per 100 pt-yrs) among patients never receiving TNF antagonists. Regression analyses demonstrated that risk factors for CVD in the general population, such as older age, male gender, hypertension, diabetes, previous history of CVD, and measures of poverty significantly increased risk of CVD in RA patients (IRRs ranging from 1.5 to 5.7). Other factors affecting risk of CVD in this unadjusted analysis are presented in the table below. Variable IRR* P-value Cumulative measures of: mHAQ 1.832 0.0001 mHAQ Disability Index 1.514 0.0031 Higher DAS28 scores 1.262 0.0050 Greater severity RA (Phys-reported) 1.176 0.0258 Higher CRP levels 1.025 0.0035 Current therapy with: Prednisone vs no pred 1.600 0.0020 MTX vs no MTX 0.825 0.2240 TNF ant vs no TNF ant 0.724 0.0491 ETN vs no TNF ant 0.577 0.0256 *Unadjusted; MTX = methotrexate; ant = antagonist; ETN = etanerceptConclusion: Assessment of functional impairment and RA disease activity, in addition to traditional CV risk factors, may help to identify RA patients at greater risk for the development of CVD. In this analysis, different approaches to treatment of RA (prednisone, MTX, or TNF antagonists) are associated with different effects on CVD risk. When evaluated as a group, treatment with TNF antagonists is associated with lower IRR values for CVD in this population. Treatment with etanercept (one of the TNF antagonists) also correlates with lower IRR values for CVD in this population. Additional risk factors adjusted analyses are needed.Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 307Session: Rheumatic arthritis – other clinical aspects and comorbidity