Anticyclic Citrullinated Peptide Antibodies and Rheumatoid Factor as Risk Factors for 10-year Cardiovascular Morbidity in Patients with Rheumatoid Arthritis: A Large Inception Cohort Study

OBJECTIVE: To determine whether anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) are risk factors for 10-year cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). METHODS: Analyses were performed using data from the Nijmegen early RA inception cohort, in which patients with newly diagnosed RA, consecutively included since 1985, were regularly followed up. Anti-CCP and RF were determined at baseline (diagnosis). Outcome was the first cardiovascular disease (CVD) event [ischemic heart disease, nonhemorrhagic cerebrovascular accident (CVA), or peripheral artery disease (PAD)] after baseline as retrieved from physician diagnosis. Fatality was checked against death certificates. Cox regression including correction for baseline confounders was performed to estimate the effect of anti-CCP, RF, and their interaction on 10-year CVD-free survival. RESULTS: Of 929 patients included, 628 were anti-CCP-positive and 697 were RF-positive. During followup, with a median of 7.5 years, 162 CV events were observed (101 ischemic heart disease, 45 CVA, and 16 PAD), of which 15 were fatal. The HRadjusted for anti-CCP was 1.17 (95% CI 0.82-1.67) and the HRadjusted for RF was 1.52 (95% CI 1.00-2.30). The association of RF positivity with CVD was even stronger in the anti-CCP-negative patients: HRadjusted 2.09 (95% CI 1.18-3.71). There was no significant interaction (p = 0.098) between anti-CCP and RF. CONCLUSION: Rather than anti-CCP, presence of RF was associated with CVD in this cohort of patients with RA