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 HR adjusted for anti-CCP was 1.17 (95% CI 0.82–1.67) and the HR adjusted 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: HR adjusted 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.