Evaluation of NT-proBNP and High Sensitivity C-Reactive Protein for Predicting Cardiovascular Risk in Patients with Arthritis Taking Longterm Nonsteroidal Antiinflammatory Drugs

OBJECTIVE: Patients with arthritis frequently are at increased risk for future cardiovascular (CV) events. We investigated the performance of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) for predicting CV events in patients with arthritis taking chronic nonsteroidal antiinflammatory drugs (NSAID). METHODS: We evaluated 2-year CV outcomes in a prospective, nested biomarker study among patients (N = 6273) with rheumatoid arthritis and osteoarthritis treated with NSAID in the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) trial. Patients were stratified by quartiles of baseline NT-proBNP and established cutpoints of NT-proBNP and hsCRP. RESULTS: NT-proBNP demonstrated a strong graded relationship with CV outcomes, including CV death (p for trend < 0.0001), myocardial infarction (MI) (p for trend = 0.02), heart failure (HF) (p for trend < 0.0001), and a composite of thrombotic events (CV death, MI, stroke) or HF (p for trend < 0.0001). Baseline levels of hsCRP were not associated with CV events (CV death/MI/stroke/HF; p for trend = 0.65). NT-proBNP remained strongly predictive of CV events after adjustment for age, sex, diabetes, hypertension, hyperlipidemia, smoking, type of arthritis, body mass index, creatinine clearance, history of CV disease, and hsCRP (CV death/MI/stroke/HF: Q4 vs Q1 hazard ratio 3.53, 95% CI 1.89-6.58). Patients with a NT-proBNP level below 100 pg/ml had a 0.94% rate of thrombotic events or heart failure at 2 years. CONCLUSION: NT-proBNP is a simple and robust noninvasive indicator of CV risk in patients with arthritis. Risk stratification based on NT-proBNP may facilitate identification of patients with arthritis who are at low CV risk during chronic NSAID treatment.