Key Points:

• In conjunction with other clinical information, the rapid BNP test significantly improves the evaluation and treatment of acute dyspnea. • Plasma natriuretic peptide levels predict the risk of death and cardiovascular events in the general population.

BASEL, SWITZERLAND—Blood tests for B-type natriuretic peptides (BNP) are showing diagnostic and prognostic capabilities that could facilitate the management of acute dyspnea and cardiovascular disease. At present, these biomarkers are used predominantly to confirm or exclude a diagnosis of congestive heart failure.

In a recent study of patients with acute dyspnea, for example, the rapid test for BNP shortened the time to initiation of the most appropriate therapy, reduced the need for hospitalization and intensive care, and led to faster discharge.[1] “It also lowered the cost of treatment,” noted lead investigator Christian Mueller, MD. The mean total cost of treatment was $5,410 for the patients whose clinical assessments included BNP testing versus $7,264 for the controls, said Dr. Mueller, an Assistant Professor of Medicine at the University of Basel in Switzerland.

A report from the Framingham Offspring Study extends the use of BNP measurements further. It showed that among persons in the general population, plasma BNP levels strongly predict the risk of death, first major cardiovascular event, heart failure, atrial fibrillation, stroke, or transient ischemic attack (TIA).[2]

“Interestingly, we saw risk increases at BNP values that were within the so-called normal range,” remarked Ramachandran S. Vasan, MD, one of the investigators and an Associate Professor of Medicine at the Boston University School of Medicine. Indeed, BNP levels exceeded 80 pg/mL in only 2.2% of the men and 1.5% of the women in the study.

DYSPNEA EVALUATION

Dr. Mueller’s study included 452 patients who presented to the emergency department (ED) with acute dyspnea that appeared unrelated to trauma. The patients were prospectively randomized to conventional evaluation plus a rapid BNP assay or to conventional evaluation alone (the control group). Conventional evaluation generally included a clinical history, physical examination, electrocardiography, pulse oximetry, chest films, and blood tests.

In the patients assigned to BNP measurements, a 5-mL venous blood sample was tested using a 15-minute fluorescence immunoassay. BNP is a polypeptide secreted by cardiac ventricular myocytes in response to volume expansion and pressure overload.

In keeping with accepted practice, the investigators considered heart failure to be an unlikely cause of dyspnea when the rapid test showed a BNP level below 100 pg/mL; heart failure was seen as likely when the BNP value exceeded 500 pg/mL. When it was between 100 and 500 pg/mL, the study protocol advised the use of clinical judgment and further tests, if necessary, to rule out COPD, stable baseline left ventricular dysfunction, and other conditions that can cause acute dyspnea. In no patient were treatment decisions based on BNP levels alone.

The two study groups were closely matched in terms of baseline demographic and clinical characteristics. About half the patients in both groups had histories of hypertension, coronary artery disease, and any pulmonary disease; about one third of them had a history of COPD.

The median time from ED presentation to the start of best treatment was 63 minutes in the BNP group and 90 minutes in the controls. Statistically significant differences between the two groups were also seen in their rates of hospitalization (75% vs 85%) and ICU admission (15% vs 24%), as well as their median times to discharge (eight vs 11 days). As a result of these differences in treatment, mean associated costs were almost $2,000 lower in the BNP group than in the controls. In-hospital mortality rates—6% in the BNP group and 9% in the controls—were not significantly different, however. Thirty-day follow-up data suggested that the two groups had similarly low rates of readmission and mortality.

The findings of this and other studies suggest that BNP testing should be included in guidelines for heart failure diagnosis, Dr. Mueller and colleagues said. They cautioned, however, that more studies are needed to optimize the use of BNP measurements in clinical practice, given that clinical experience with them is still limited.

CARDIOVASCULAR RISK

The Framingham Offspring Study is a continuation of the landmark Framingham Heart Study. Dr. Vasan and colleagues used data from 3,346 of the participants in the Offspring Study; these people had attended the sixth examination cycle (between 1995 and 1998) and had undergone measurements of BNP and N-terminal pro-atrial natriuretic peptide levels. (The latter biomarker, as its name implies, is released primarily by the atria in response to wall stretch.)

During follow-up, which averaged 5.2 years, 119 participants died and 79 experienced a first major cardiovascular event. A direct correlation was seen between the plasma natriuretic peptide levels and the rates of death and first major cardiovascular events; however, BNP was the better of the two biomarkers in predicting risk.

After adjusting their analysis for cardiovascular risk factors, the researchers found that each incremental increase in the BNP level (defined as one standard deviation in the log value) elevated the risks of death and a first major cardiovascular event by 27% and 28%, respectively. In addition, it markedly raised the risks of heart failure, atrial fibrillation, and stroke or TIA. BNP levels above the 80th percentile—20 pg/mL for men and 23.3 pg/mL for women—were also associated with increased risk. However, no association was seen between elevated BNP levels and the risk of events resulting from coronary heart disease.

Dr. Vasan and colleagues acknowledge that their findings need to be confirmed in other studies. However, they believe that BNP measurements provide prognostic information that is additional to that derived from assessment of traditional cardiovascular risk factors.

—Timothy Begany

References
1. Mueller C, Scholer A, Laule-Kilian K, et al. Use of a B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med. 2004;350:647-654.
2. Wang TJ, Larson MG, Levy D, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350:655-663.

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