By Harold L. Karpman, MD, FACC, FACP

Clinical Professor of Medicine, UCLA School of Medicine

Dr. Karpman reports no financial relationships relevant to this field of study.

SYNOPSIS: Elevated BNP values in a large cohort of women with numerous CV events modestly improved measures of CVD risk prediction.

SOURCES: Everett BM, et al. B type natriuretic peptides improve cardiovascular disease risk prediction in a cohort of women. J Am Coll Card 2012;64:1789-1797; Iwanga Y, et al. B type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: Comparison between systolic and diastolic heart failure. J Am Coll Cardiol 2006;47:742-748.

Measurement of B-type natriuretic peptides (BNP) values have gained acceptance as a tool for diagnosis and risk stratification in patients experiencing shortness of breath and chest pain.1-3 Elevated BNP levels have demonstrated a consistent association with adverse cardiovascular outcomes in stable patients with and without established cardiovascular disease (CVD),4 but only a few studies have examined whether BNP levels improve clinical risk prediction in the general population.5-8

Recognizing that women have a higher level of BNP values than do men,5 and yet have a lower absolute risk for CVD than men of similar age and risk factor burden,9 Everett and colleagues decided to evaluate the relationship between BNP values and incident CVD in women. They analyzed a prospective case cohort within the Women’s Health Initiative (WHI) observational study, which is a multi-ethnic cohort of 93,676 postmenopausal women ages 50-79 who were enrolled between 1994 and 1998 at 40 sites across the United States. BNP levels were obtained at baseline in 1821 women who subsequently had a major cardiovascular event, and the BNP value in this group was compared to BNP values obtained from a reference cohort of 1992 women. The results of the study determined that the BNP values modestly improved measures of CVD risk prediction.


Data supporting BNP values as a cardiovascular risk predictor have been predominantly derived from male cohorts.4 Two randomized, controlled trials10,11 that were recently published demonstrated the efficacy of primary prevention strategies focused on patients with elevated BNP levels, thereby demonstrating the potential utility of BNP-based risk predictions. Recognizing that women were under-represented in the current cardiovascular risk prediction literature, Everett and colleagues carefully analyzed the data from the WHI, which is a large, carefully characterized cohort with a high prevalence of events providing tremendous power to investigate risk prediction among women who were otherwise under-represented in the current literature. The “hard” endpoints that they used were a composite of cardiovascular death, myocardial infarction, and stroke (congestive heart failure was not included). Although the present study results contribute important information to help refine risk prediction, many important clinical questions remain unanswered, including those related to pathophysiology and clinical translation. Our current understanding of BNP levels is that they are primarily related to ventricular wall stress, and it remains unclear why BNP values should be predictive of the primary endpoint components utilized in this study. Further investigation into the underlying mechanism of why elevated BNP values are associated with an increased frequency of CVD may eventually shed some light on cardiovascular event pathogenesis.

In summary, the results of the Everett study may prove to be clinically useful because recent studies have suggested that targeting intensified cardiovascular care on the basis of multiple clinical measurements, including BNP levels, can reduce cardiovascular events,10,11 at least in high-risk populations. Adding BNP measurements to the growing list of risk factors may, therefore, prove to be quite beneficial in the long term.  




1. Maisel AS, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347:161-167.

2. Januzzi JL, et al. The N-terminal pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 2005;95:948-954.

3. Thygesen K, et al. Recommendations for the use of natriuretic peptides in acute cardiac care: A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. Eur Heart J 2012;33:2001-2006.

4. Di Angelantonio E, et al. B-type natriuretic peptides and cardiovascular risk: Systematic review and meta-analysis of 40 prospective studies. Circulation 2009;120:2177-2187.

5. Olson MH, et al. N-terminal pro- brain natriuretic peptide, but not high-sensitivity C-reactive protein improves cardiovascular risk prediction in the general population. Eur Heart J 2007;28:1374 -1381.

6. Zethelius B, et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008;358:2107-2116.

7. Melander O, et al. Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA 2009;302:49-57.

8. Blankenberg S, et al. Contribution of 30 biomarkers to 10-year cardiovascular risk estimation into population cohorts: The MONICA, risk, genetics, archiving and monographs (MORGAM) biomarker project. Circulation 2010;121:2388-2397.

9. National Heart, Lung, and Blood Institute. Incidence and Prevalence: 2006 Chart Book on Cardiovascular and Lung Diseases. Available at: Accessed August 14, 2013.

10. Ledwidge M, et al. Natriuretic peptide-based screening and collaboration care for heart failure: The STOP-HF randomized trial. JAMA 2013;310:66-74.

11. Huelsmann M, et al. PONTIAC (NT-proBNP selected prevention of cardiac events in population of diabetic patients without a history of cardiac disease): A prospective randomized controlled trial. J Am Coll Card 2013;62:1365-1372.