Received on September 5, 2007
Accepted on April 4, 2008

General Clinical Chemistry

The Concentration of N-Terminal Pro–B-type Natriuretic Peptide Predicts the Risk of Cardiovascular Adverse Events from Antiinflammatory Drugs: A Pilot Trial

¹ Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany
² Department of Internal Medicine, University Hospital of Heidelberg, Heidelberg, Germany
³ DIAneering GmbH, Diagnostics Engineering, Research and Know-How Services, Heidelberg, Germany
⁴ Cardiovascular Division, Department of Internal Medicine and Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Medical School, Rochester, MN

^* To whom correspondence should be addressed. E-mail: jaffe.allan{at}mayo.edu.

BACKGROUND: We investigated whether higher concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs.

METHODS: NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs.

METHODS: We observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95-fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations 100 ng/L than in patients taking any inhibitor who had NT-proBNP values <100 ng/L (P < 0.05). Patients taking coxibs (alone or in addition to tNSAIDs or glucocorticoids) with baseline NT-proBNP values 100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values <100 ng/L (P < 0.01). Patients who were taking 2 or more antiinflammatory drugs and had NT-proBNP values 100 ng/L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values <100 ng/L (P < 0.05). An NT-proBNP value <100 ng/L was associated with negative predictive values of >85% across all treatment groups.

CONCLUSIONS: NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.