N-Terminal Pro-Brain Natriuretic Peptide Is a More Useful Predictor of Cardiovascular Disease Risk Than C-Reactive Protein in Older Men With and Without Pre-Existing Cardiovascular Disease

Study Questions:

What is the relative predictive capability of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (CRP) for risk of cardiovascular disease (CVD) in older men with and without pre-existing CVD?

Methods:

This study was conducted within The British Regional Heart Study, a prospective study of CVD involving 7,735 men who were screened between 1978 and 1980, ages 40-59 years, in British towns, and who survived and participated in a 20-year follow-up, at which time an NT-proBNP and CRP was obtained. Presence of CVD was established by patient history, medical records, and electrocardiogram, and medications were documented. Cause of death was based on the coded National Health Service registry.

Results:

A total of 3,649 men ages 60-79 years were followed for an additional 9 years, during which there were 608 major CVD events (major fatal and nonfatal coronary heart disease, stroke, and CVD death). NT-proBNP was significantly associated with risk of all major CVD outcomes after adjustment for CV risk factors in both men with and without CVD. The adjusted standardized hazard ratios for CVD events in those without pre-existing CVD and those with pre-existing CVD were 1.49 (95% confidence interval [CI], 1.33-1.65) and 1.52 (95% CI, 1.33-1.75), respectively. CRP was associated with CVD outcomes only in men without pre-existing CVD (adjusted standardized hazard ratios, 1.22; 95% CI, 1.10-1.34, and 1.00; 95% CI, 0.86-1.38, respectively). NT-proBNP was more strongly associated with CVD outcome than CRP, particularly among those with pre-existing CVD. Inclusion of NT-proBNP in a Framingham-based model yielded significant improvement in C-statistics in both men with and without CVD, and resulted in a net reclassification improvement of 8.8% (p = 0.0009) and 8.2% (p < 0.05), respectively, for major CVD events. Inclusion of CRP in the Framingham-based model did not improve prediction in either group (net reclassification improvement 3.8% and 0.6%, respectively).

Conclusions:

NT-proBNP, but not CRP, improved prediction of major CVD events in older men with and without existing CVD.

Perspective:

Novel biomarkers and classic coronary risk factors have each been able to identify persons at higher risk within a population, and do so as relative risk but not absolute risk. The holy grail is the ability to characterize the annual risk in an individual, which is beyond the ability of all available risk predictors. It is important to realize that this study comparing NT-proBNP and CRP was conducted in older men. It is not surprising that a biomarker of cardiac wall stress is a better marker of CV outcomes than a marker of inflammation. The findings would not support routine use of NT-proBNP for risk stratification.

Keywords: Inflammation, Stroke, C-Reactive Protein, Follow-Up Studies, Biological Markers, Cardiovascular Diseases, Coronary Disease, Risk Factors, Electrocardiography, Natriuretic Peptide, Brain


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