High-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide in patients with stable coronary artery disease: a prognostic study within the CLARICOR Trial

Abstract

Background. Patients with stable coronary artery disease (CAD) have a poor prognosis. The aim of the study was to evaluate the extent to which serum high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement alone or together could be prognostic biomarkers in patients with stable CAD. Materials and methods. During the 2.6-year follow-up period 270 patients among the 4264 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 cardiovascular deaths (CVD)). Results. Serum NT-proBNP was significantly associated with MI (hazard ratio (HR), 1. 65 (refers to a 2.72 fold increase in serum level, p = 0.0005), CVD (HR, 2.42, p < 0.0005) and non-CVD (HR, 1.79, p < 0.0005). When correcting for hs-CRP, NT-proBNP was still significantly associated with MI (HR, 1.63, p = 0.0005), CVD (HR, 2.36, p < 0.0005) and non-CVD (HR, 1.66, p < 0.0005). Serum hs-CRP was compared to NT-proBNP less associated with MI (HR, 1.20, p = 0.001), CVD (HR, 1.39, p < 0.0005) and non-CVD (HR, 1.67, p < 0.0005). When corrected for NT-proBNP, hs-CRP was only associated with non-CVD (HR, 1.51, p < 0.0005). When adjusting for cardiovascular risk factors hs-CRP predicted non-CVD (HR, 1.46) and all-cause death (HR, 1.24) and NT-proBNP predicted MI (HR, 1.50), CVD (HR, 1.98), non-CVD (HR, 1.39), and all-cause death (HR, 1.62)(p < 0.0005 for all). Conclusion. Increased serum NT-proBNP was a stronger predictor of MI, cardiovascular death and non-cardiovascular death than hs-CRP in patients with stable CAD. Once NT-proBNP was taken into account, hs-CRP did not improve predictions.

Trial registration: ClinicalTrials.gov identifier: NCT00121550.

Key Words::

• Biomarker
• coronary artery disease
• heart disease
• prognostic factors
• hs-CRP
• NT-proBNP

Acknowledgements

We thank T. L. Hansen and S. Birch, Copenhagen Trial Unit, for assistance with the figures.

Funding sources and disclosures

The CLARICOR trial is an investigator-initiated trial supported by grants from non-profit funds including the Danish Heart Foundation, Copenhagen Hospital Corporation, Danish Medical Research Council, the 1991 Pharmacy Foundation, and The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet. Abbott Laboratories, IDC, Queensborough, UK, supplied the clarithromycin and placebo tablets.

The hs-CRP and NT-proBNP study was supported by grants from the Heart Centre Research Foundation at Rigshospitalet, Copenhagen University Hospital (JK) and The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet (JK).

Roche Diagnostics provided the study with some of the NT-proBNP assay kits. Roche Diagnostics had no role in design and conduction of the study, in collection, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript.

Clinical Trials.gov (NCT00121550)

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.