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Heart Failure
Amino-terminal Pro-B-type Natriuretic Peptide Testing—
Past, Present, and Future Applications
a report by
Shanmugam Uthamalingam, MD
1
and James L Januzzi, Jr, MD
1,2
1. Cardiology Division, Massachusetts General Hospital; 2. Harvard Medical School, Boston, Massachusetts
Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is one of due to age-associated diastolic dysfunction of the heart along with declining
the natriuretic peptide family of hormones that play a vital role in the glomerular filtration rate (GFR),
28
while the difference between the sexes is
regulation of circulatory volume and pressure, reducing activity of probably related to the effects of androgens on the concentration of natriuretic
the renin–angiotensin–aldosterone system and minimizing myocardial fibrosis peptides, such that men have lower values for BNP and NT-proBNP.
46
With
in the setting of heart muscle stretch. Therefore, natriuretic peptides exert respect to renal function, NT-proBNP is partially renally excreted, and hence
favorable effects on the heart in the context of heart failure (HF), and recent with declining renal function increasing levels of NT-proBNP are observed.
data suggest that the measurement of natriuretic peptide concentrations in How much of the measurable NT-proBNP present in the circulation of patients
patients with both acute and chronic HF not only aids in the diagnosis and with impaired renal function is related to structural heart disease in these
prognosis of HF in both symptomatic and asymptomatic patients, but may patients remains speculative; however, prognostic studies argue that the
also be useful in their clinical management. In recognition of the importance majority of the NT-proBNP signal measured in patients with chronic kidney
of NT-proBNP as an adjunct to the diagnosis, prognosis, and management of disease is in fact a ‘true positive’ value, as concentrations of NT-proBNP vary
patients with heart disease, NT-proBNP has been added to numerous widely among patients with similar levels of renal dysfunction and are
guideline statements,
1–4
and an international consensus panel recently powerfully prognostic when elevated.
30–44
Lower than expected natriuretic
published recommendations for its optimal use.
5,6
This article will discuss the peptide values may be seen in normal patients who are overweight; there is
up-to-date understanding of NT-proBNP as a tool for HF applications. an inverse relationship between BMI and NT-proBNP levels.
25
This is probably
due to reduced release of NT-proBNP, as similar BMI-associated reductions in
Natriuretic Peptide Biology BNP are observed (and NT-proBNP and BNP are cleared in a different
Recent changes in the understanding of BNP and NT-proBNP biology have led manner).
45,46
The participation of increased activity of natriuretic peptide
to the recognition that what is measured clinically by assays designed to detect clearance receptor located in the adipose tissue remains debatable.
29
these analytes is actually a mixture of degraded BNP, NT-proBNP, and an
un-cleaved precursor protein (which lacks the biological activity of BNP) called NT-proBNP Testing for Diagnostic Evaluation of
proBNP. That clinical assays cross-react with proBNP remains purely speculative; Symptomatic Primary Care Patients
however, data argue that there is no clear advantage of direct measurement of Studies have analyzed the role of utilizing NT-proBNP levels to exclude HF in
un-cleaved proBNP over clinical assays for NT-proBNP.
7
the evaluation of primary care patients presenting with dyspnea.
47–51
In this
Role of NT-proBNP in the Diagnosis of Heart Failure
Shanmugam Uthamalingam, MD, is a faculty member in the
Abundant data indicate that NT-proBNP is valuable for the diagnostic
Department of Internal Medicine at Dartmouth-Hitchcock Clinic,
evaluation of HF in asymptomatic patients and those presenting with acute Manchester, New Hampshire, an affiliate of Dartmouth Medical
dyspnea. It is important to note that as a sensitive indicator of structural heart
School. He is currently working on various projects as a research
assistant for Dr Januzzi. He is a graduate of Madras Medical
disease, NT-proBNP may be elevated in a variety of clinical conditions, including
College and completed his residency at National Health System,
non-systolic heart muscle diseases, valvular heart disease, atrial arrhythmias, UK, and Sound Shore Medical Center of Westchester, an affiliate
anemia, septic shock and shock due to other causes, ischemic stroke, and
of New York Medical College.
pulmonary hypertension
8–22
(see Table 1). In each of these cases, irrespective of
diagnosis, NT-proBNP has been shown to be prognostically meaningful.
James L Januzzi, Jr, MD, is an Associate Professor of Medicine at
Harvard Medical School and Director of the Cardiac Intensive
Care Unit at Massachusetts General Hospital. He is an active
Factors with Effects on NT-proBNP Values clinical trialist, performing several studies on cardiac biomarker
When considering the value of NT-proBNP testing in apparently healthy
testing, and has contributed significantly to the understanding
of natriuretic peptide testing in a broad array of situations,
individuals, it is necessary to recognize that concentrations of this biomarker
including acute heart failure. Dr Januzzi was the top-ranked
are considerably lower in those without structural heart disease and thus more graduate in his class at New York Medical College. He
likely to be affected by processes with subtle effects on NT-proBNP, such as age,
completed an internship and residency at Brigham and Women’s
Hospital prior to performing a clinical and research fellowship in
sex, renal function, and body mass index (BMI).
23–46
As an example, among
cardiovascular medicine at the Massachusetts General Hospital,
healthy patients aged 45–59 and ≥60 years, the mean values of NT-proBNP
where he also completed a fellowship in cardiac ultrasound.
were identified to be 28 and 61ng/l, respectively, or 53 or 86ng/l for male and
E: jjanuzzi@partners.org
females, respectively.
23
The age-associated increase in NT-proBNP levels may be
© TOUCH BRIEFINGS 2008
61
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