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13
| 1 | 2005
Klinisk Biokemi i Norden
to unspecific to use as an aid in the diagnosis of
breathlessness of uncertain cause (7) others have
found it reasonable to make use of it (8) as long as
potential confounders are kept in mind (9).
The BNP (Breathing Not Properly) Multinational
Study was a 7-center, prospective study of 1586
patients brought to an emergency department with
acute dyspnea (10). This study found BNP levels by
themselves to be more accurate than any historical
or physical findings or laboratory values in identi-
fying congestive heart failure as the cause of dys-
pnea. The diagnostic accuracy of BNP at a cutoff of
100 pg/ml was 83.4 % and negative predictive value
of BNP less than 50 pg/ml was 96 %.
The BASEL study (B-Type Natriuretic Peptide for
Acute Shortness of Breath Evaluation) took a some-
what different viewpoint. This was a study of 452
patients who came to the emergency department
with acute dyspnea: half were randomly assigned
to a diagnostic strategy involving the measurement
of BNP levels with the use of a rapid bedside assay,
and half were assessed in a standard manner. The
time to discharge and the total cost of treatment
were the primary end-points.
The findings suggested that used in conjunction
with other clinical information, rapid measurement
of BNP in the emergency department could improve
the evaluation and treatment of patients with acute
dyspnea and thereby reduce the time to discharge
and the total cost of treatment (11).
Even more recently the primary findings of the
REDHOT study (Rapid Emergency Department Heart
Failure Outpatient Trial ) were that BNP level was
a strong predictor of 90-day outcome in patients
seeking acutely with heart failure, whereas indeed
the attending doctor’s intention to admit or dis-
charge had no influence (12).
Although a disappointment for standard bedside
assessment this may reflect the ability of BNP to
measure risk factors not readily seen clinically. This
is supported by the findings of Bettencourt et al.
(13) and later Lubien et al (14) who showed that
BNP levels had excellent accuracy for the diagnosis
of isolated diastolic HF, a diagnosis that otherwise
can be tricky to make.
Prognostic value in heart diseases
The plasma level of BNP has been evaluated as a
prognostic marker in various heart conditions, most
thoroughly in heart failure. BNP correlates with
NYHA functional class, where circulating levels
of BNP range between ~200 pg/mL in class I and
~1000 pg/mL in class IV (15). BNP has been shown
to be a prognostic marker of mortality and mor-
bidity in chronic heart failure (16) and serial BNP
measurements during the treatment of acute heart
failure provide incremental prognostic information
over clinical presentation and repetitive echocardio-
graphic examination. (17).
In patients with heart transplants, BNP levels<800
pg/ml predicted a middle-term good survival (18)
De Lemos et al. (19) demonstrated the ability of
BNP, measured within a few days of an acute coronary
syndrome, to predict the risk of mortality, clinical heart
failure, and a new myocardial infarction. These find-
ings were later supported by Richards et al. (20) who
also found BNP to be independent of left-ventricular
ejection fraction as a risk factor in this aspect.
Yet another attribution to BNP as a prognostic
marker was made by the study of Omland et. al
who found that in patients with clinically stable
coronary artery disease, plasma BNP levels were
independently related to long-term survival. (21).
This finding has now been confirmed by other
investigators in a larger survey (22).
Treatment evaluation
Prognostic markers have limited value in themsel-
ves; the value utterly depends on if their measure-
ment can influence management significantly in a
positive way.
A number of studies have shown BNP levels in
both acute and chronic heart failure to be influ-
enced favourable by treatment. Recently Conraads
et al. showed that combined endurance/resistance
training was able to reduce BNP levels in patients
with chronic heart failure (23).
Scarcer are studies that are designed to use BNP
to guide treatment but these are too beginning to
appear. In a relativley small trial, 69 patients with
NYHA class II – IV symptoms were randomized to
treatment guided by either plasma BNP concen-
tration or standardized clinical assessment. Mean
follow-up was 9.5 months. The BNP group had
significantly fewer cardiovascular events compared
to clinical assessment only. (24)
A larger trial is underway to evaluate the usefulness
of BNP to guide therapy, the BNP-Assisted Treatment
