The Clinical Role of BType Natriuretic Peptide

1
The Clinical Role of B-Type Natriuretic Peptide
2

Review Objectives

• To describe the natriuretic peptide system and
  its role in congestive heart failure (CHF)
• To specifically review B-type natriuretic peptide
  (BNP) as a uniquely valuable neurohormonal marker
• To review recently published data on BNP as a
  diagnostic tool in congestive heart failure and
  risk stratification in patients with acute
  coronary syndromes

3
Presentation Overview

• The healthcare burden of congestive heart failure
• The natriuretic peptides
• BNP clinical studies

4
The Healthcare Burden of Congestive Heart Failure
5
Hospitalization and Congestive Heart Failure

• Major public health problem worldwide
• Most frequent cause of hospitalization in
  patients older than 65 years
• Fourth leading cause of adult hospitalization in
  U.S.
• DRG 127 (Congestive Heart Failure)
• Primary diagnosis 1,000,000 hospitalizations/yr
• Secondary diagnosis 2,000,000
  hospitalizations/yr

6
CHF Patient Population by NYHA Class
Class I No limitations of physical
activity Class II Slight limitations of physical
activity Class III Marked limitations of
physical activity Class IV Inability to carry
out physical activities without discomfort
Class IV 240,000 (5)
Class II 1,680,000 (35)
Class III 1,200,000 (25)
Class I 1,680,000 (35)
Source American Heart Association.
7
HCFA Hospitalization Costs
Billions of
OConnell JB, et al. J Heart Lung Transplant.
199413S107-S112..
8
The Natriuretic Peptides
9
Natriuretic Peptides
10
Natriuretic Peptides Origin and Stimulus of
Release
Peptide Primary Origin Stimulus of
Release ANP Cardiac atria Atrial
distension BNP Ventricular myocardium Ventricular
stretch / Volume overload CNP Endothelium
Endothelial stress
ANP Atrial Natriuretic Peptide BNP B-type
Natriuretic Peptide CNP C-type Natriuretic
Peptide
Adapted from Burnett JC. J Hypertens.
200017(Suppl 1)S37-S43.
11
Release of BNP From Cardiac Myocytes
preproBNP (134 aa)
proBNP (108 aa)
signal peptide (26 aa)
MYOCYTE
secretion
BNP (77-108)
NT-proBNP (1-76)
12
BNP vs. NT-ProBNP

• BNP is biologically active
• BNP is an active hormone that promotes
  natriuresis and diuresis in response to
  RAA-induced vasoconstriction
• NT-ProBNP is the inactive molecule resulting from
  cleavage of the prohormone Pro-BNP
• BNP is a suitable marker in patients with renal
  insufficiency
• Clearance of NT-ProBNP is dependent on kidney
  function while BNP is cleared by binding to
  natriuretic peptide receptors (NPRs) and neutral
  endopeptidase (NEP)
• BNP accurately reflects current ventricular
  status
• The half-life of NT-ProBNP is 1 to 2 hours vs. 20
  minutes for BNP

13
B-Type Natriuretic Peptide (BNP)

• Found in the cardiac ventricles
• Released in response to stretch and increased
  volume in the ventricles
• BNP levels are related to
• Left ventricular end-diastolic pressure
• NYHA classification

14
BNP vs. EF by Echocardiography
100
80
y -0.7, Plt0.001
60
LVEF ()
40
20
0
0
1.0
2.0
3.0
Log BNP (pmol/L)
Davis, et al. Lancet. 1994343440-444.
15
BNP Clinical Studies
16
BNP Measurement

• Studies reviewed here used the Triage BNP Test
  from Biosite Incorporated
• A rapid (approx 15 minutes) point-of-care test
• The test uses 250 µL of whole blood or plasma
• Produces quantitative results
• Built-in test controls
• Requires the Triage MeterPlus

17
Test Platform

• The Triage MeterPlus
• Runs individual Test Devices (such as BNP)
• Built-in QC, QA functions
• Quantitative measurements
• Portable system

The Triage MeterPlus Platform
18
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19
Utility of B-Type Natriuretic Peptide in the
Diagnosis of Congestive Heart Failure in an
Urgent-Care Setting

• Dao Q, Krishnaswamy P, et al.
• Journal of the American College of Cardiology.
• Vol. 37, No. 2, 2001.

20
Methods

• 250 patients presenting to the ED with shortness
  of breath
• Consent signed
• Data recorded history, physical exam, lab tests
• ED assessment
• BNP values recorded and blinded to physicians
• Later assessment The Gold Standard
• 2 cardiologists with access to any later tests
  (echocardiograms), hospital course, response to
  Rx, etc...

Dao Q, et al. J. Am Cardiol. 200137.
21
BNP Levels in Patients Diagnosed Without CHF,
With Baseline Left Ventricular Dysfunction, and
With CHF
1076 138
141 31
38 4
N 139 N 14 N 97
Dao Q, et al. J. Am Cardiol. 200137.
22
BNP Concentration and the Degree of CHF Severity
2013 266
BNP Concentration (pg/mL)
791 165
186 22
Mild
Moderate
Severe
n 27
n 34
n 36
CHF Severity
Dao Q, et al. J. Am Cardiol. 200137.
23
Hospital Admission vs. BNP
700 116
254 60
N 142 N 108
Dao Q, et al. J. Am Cardiol. 200137.
24
Univariate Analysis of BNP Levels
Positive Negative Predictive Predictive
Variable Sensitivity Specificity Value
() Value () Accuracy
BNP Level (pg/mL) 80 98 (93-100) 92 (86-96) 90
(82-94) 98 (94-100) 95 100 94 (89-97) 94
(89-97) 92 (85-96) 96 (91-98) 94 115 90
(83-95) 96 (91-98) 94 (87-97) 94
(88-97) 94 120 90 (82-95) 96 (92-99) 95
(88-98) 93 (88-96) 94 150 87 (78-92) 97
(93-99) 95 (89-98) 91 (85-95) 93
Dao Q, et al. J. Am Cardiol. 200137.
25
Correction of Misdiagnosed Cases Using BNP at 80
pg/mL
Number of Patients With
the Indicated BNP Levels
Number of
Mean BNP
Diagnoses
Patients
Concentration
gt80 pg/mL
lt80 pg/mL
Overdiagnosed
15
46 13
1
14
Underdiagnosed
15
747 337
15
0
Dao Q, et al. J. Am Cardiol. 200137.
26
Study Conclusions

• BNP levels accurately reflect the cause of
  dyspnea in patients presenting to the emergency
  department
• BNP levels add additional information to that
  gathered by the physician, allowing for the
  correct and rapid diagnosis of congestive heart
  failure

Dao Q, et al. J. Am Cardiol. 200137.
27
BNP Multinational Study
A Prospective, Blinded Trial of B-Type
Natriuretic Peptide as a Diagnostic Test for the
Emergency Diagnosis of Heart Failure
Rapid Measurement of B-Type Natriuretic Peptide
in the Emergency Diagnosis of Heart
Failure Maisel A, Krishnaswamy P, et al. The New
England Journal of Medicine. Vol. 347, No. 3.
July 18, 2002.
28
BNP Multinational Study
Study Organization Alan Maisel, M.D., Principal
InvestigatorPeter A. McCullough, M.D., M.P.H.,
Co-Principal Investigator
Endpoints Committee James McCord, M.D.
(Chair) Alan S. Maisel, M.D. Howard C. Hermann,
M.D. Philippe Duc, M.D. Torbjorn Omland, M.D.
William T. Abraham, M.D. Alberto Perez, M.D.
Steering Committee Alan S. Maisel, M.D.
(Chair) Peter A. McCullough, M.D., M.P.H. Richard
M. Nowak, M.D., M.B.A. (Emergency Medicine) James
McCord, M.D. Judd E. Hollander, M.D. (Emergency
Medicine) Philippe Duc, M.D. Torbjorn Omland,
M.D. Alan B. Storrow, M.D. (Emergency
Medicine) William T. Abraham, M.D. Alan H.B. Wu.,
Ph.D. (Laboratory Medicine)
29
Study Design

• Prospective, blinded, diagnostic test evaluation
  carried out from April 1999 to December 2000
• Inclusion Criteria
• Age gt18
• Dyspnea as primary reason for emergency
  department visit
• Able to give informed consent
• Exclusion Criteria
• Hemodialysis or peritoneal dialysis
• Acute myocardial infarction
• Overt cause of dyspnea clearly secondary to CHF

30
Measurements

• Data Collection by Trained ED Research Personnel
• Baseline demographics
• Clinical history
• Objective clinical exam signs recorded
• ED Pre-Test Probability
• ED physician, at the time of disposition,
  indicated the level of clinical certainty that
  CHF was the cause of dyspnea on a visual analogue
  scale

31
Reference Standard for Heart Failure Diagnosis

• Two Independent Cardiologists
• Blinded to BNP levels
• All clinical information available from ED and
  hospitalization (echo, cath, response to
  treatment)
• Completed a checklist of signs and symptoms so
  that Framingham and NHANES scores could be
  completed
• If no agreement, adjudication by Endpoints
  Committee
• Final Diagnoses
• Dyspnea due to CHF
• History of CHF, but dyspnea due to other cause
  (eg, anemia, sepsis, etc)
• Dyspnea not due to CHF

32
Mean BNP Levels by Final Adjudicated Diagnosis
BNP Concentration (pg/mL)
N 1586
Non-CHF Dyspnea
CHF-Related Dyspnea
LVD (Non-Cardiac S.O.B.)
n 744
n 770
n 72
33
Secondary Endpoint
Area Under the Receiver Operating Characteristic
Curve
Not Meaningful
Good
Excellent
34
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35
Decision Statistics
Positive Predictive Value ()
Negative Predictive Value ()
BNP (pg/mL)
Sensitivity ()
Specificity ()
50
97 (96-98)
62 (59-66)
71 (68-74)
96 (94-97)
80
93 (91-95)
74 (70-77)
77 (75-80)
92 (89-94)
100
90 (88-92)
76 (73-79)
79 (76-81)
89 (87-91)
125
87 (85-90)
79 (76-82)
80 (78-83)
87 (84-89)
150
85 (82-88)
83 (80-85)
83 (80-85)
85 (83-88)
36
Primary Endpoint
N 1538 with ED probability of CHF recorded
P lt 0.0001 for BNP vs. Clinical Judgment or
Combined vs. Clinical Judgment
37
BNP vs. NHANES and Framingham Criteria
Comparative Accuracy
N 1586
38
BNP Combined With Clinical Judgment
BNP Improves Diagnostic Accuracy
AUC .86 (.84-.88) ED Probability .90 (.88-.91)
BNP .93 (.92-.94) Combined
39
Frequency Histogram
Clinical Probability of CHF (Blinded to BNP)
Pretest Probability of CHF
40
Clarification of Diagnosis and BNP
BNP Reduces Clinical Uncertainty by 74
Plt 0.0001
41
Multivariate Analysis of Diagnostic Methods
Chi-Square
Significance
Odds Ratio
Variable
Hx CHF
404.6
lt0.001
22.0
141.6
15.5
Cephalization-c
lt0.001
91.3
4.9
lt0.001
Edema
Rales
36.1
3.0
lt0.001
Hx MI
32.6
3.2
lt0.001
Age gt70
18.8
2.2
lt0.001
JVD
15.8
2.6
lt0.001
Third heart sound
13.5
4.9
lt0.001
Orthopnea
10.0
1.8
lt0.001
Atrial fibrillation
11.3
3.0
lt0.001
BNP gt100 pg/mL
225.0
28.9
lt0.001
If BNP analyzed first
BNP 100
647.3
42.4
lt0.001
42
BNP Multinational Study Conclusions

• BNP independently adds diagnostic information to
  traditional components of the evaluation
  including history, physical exam, and chest x-ray
• BNP has a high degree of sensitivity,
  specificity, and accuracy for the diagnosis of
  heart failure
• In those patients in which clinical indecision
  exists in the ED, using BNP reduces indecision by
  74 at a cutoff of 100 pg/mL

43
The Value of a Rapid BNP Test Result

• Shortness of breath is a nonspecific symptom that
  could be indicative of many serious diseases
• Accurate diagnosis in situations where time is
  critical
• Prevents complications associated with incorrect
  treatment pathways
• Appropriate resource utilization
• Faster disposition to home or appropriate
  department
• Consultation with appropriate departments/speciali
  sts

44
Utility of BNP Peptide as a Rapid, Point-of-Care
Test for Screening Patients Undergoing
Echocardiography to Determine Left Ventricular
Dysfunction

• Maisel A, Koon J, et al.
• American Heart Journal.
• Vol. 141, No. 3, 2001.

45
Methods

• 200 subjects referred for echocardiography to
  evaluate the presence or absence of left
  ventricular dysfunction
• 62 subjects with known LVD were excluded from
  analysis
• The results of the BNP measurements were blinded
  to the cardiologists making the assessment of LV
  function

Maisel A, et al. Am Heart J. 2001141.
46
BNP and LV Function
489 75
29.5 62.4
N 105 N 95
Maisel A, et al. Am Heart J. 2001141.
47
Study Conclusions

• An easy, rapid test for BNP can reliably predict
  the presence or absence of left ventricular
  dysfunction on echocardiography
• BNP may be an excellent tool for identification
  of left ventricular dysfunction

Maisel A, et al. Am Heart J. 2001141.
48
A Rapid Test for B-Type Natriuretic Peptide
Correlates With Falling Wedge Pressures A Pilot
Study

• Kazanegra R, Cheng V, et al.
• Journal of Cardiac Failure.
• Vol. 7, No. 1, 2001.

49
Methods

• 20 decompensated CHF patients admitted to undergo
  hemodynamic monitoring
• Inclusion based on either
• New-onset CHF confirmed via cardiology using
  Framingham criteria
• Exacerbation of previously recorded CHF
• PAW pressure of gt20 mm Hg

Kazanegra R, et al. J Card Fail. 20017.
50
Relationship Between BNP Concentration and
Pulmonary Artery Wedge Pressure
Change per hour
PAW (mm Hg)
BNP (pg/mL)
Kazanegra R, et al. J Card Fail. 20017.
51
Changes in BNP and PAW Levels
Pulmonary Artery Wedge Pressure.
Kazanegra R, et al. J Card Fail. 20017.
52
Study Conclusion

• Data suggest that changes in BNP level correlate
  to changes in PAW pressure

Kazanegra R, et al. J Card Fail. 20017.
53
The Prognostic Value of B-Type Natriuretic
Peptide in Patients With Acute Coronary Syndromes

• de Lemos JA, Morrow D, et al.
• New England Journal of Medicine.
• Vol. 345, No. 14. October 4, 2001.

54
BNP as a Prognostic Tool in Acute Coronary
Syndromes

• 2525 patients from the Thrombolysis in Myocardial
  Infarction (TIMI) 16 Study
• Baseline BNP concentration was correlated to
  events at 30 days and 10 months
• Death
• Congestive heart failure
• Myocardial infarction

de Lemos JA, et al. N Engl J Med. 2001345.
55
ACS Survival by BNP Quartile Analysis
10
Quartile 4
BNP (pg/mL)
137.9 1456.6
8
6
Quartile 3
81.3 137.8
Mortality ()
4
Quartile 2
43.7 81.2
2
Quartile 1
5.0 43.6
0
0
50
100
150
200
250
300
Time (days)
de Lemos JA, et al. N Engl J Med. 2001345.
56
ACS Mortality by BNP QuartileA Unifying
Feature of Risk
P0.02 Plt0.001
Plt0.001
10-Month Mortality ()
ST Elevation Non-ST Elevation
Unstable Angina Myocardial Infarction
Myocardial Infarction
n 825
n 565 n 1133
de Lemos JA, et al. N Engl J Med. 2001345.
57
Endpoints at a BNP Cutoff of 80 pg/mL
Plt0.005 for each comparison
Percent of Patients
Death CHF MI Death
CHF MI
30 Days 10
Months
de Lemos JA, et al. N Engl J Med. 2001345.
58
Study Conclusions

• BNP measurements made within the first 72 hours
  after ischemic symptoms provide powerful risk
  stratification information across a spectrum of
  ACS
• Activation of the cardiac neurohormonal system
  may be a unifying feature among ACS patients at
  high mortality risk
• A BNP concentration of 80 pg/mL is an appropriate
  risk threshold among patients with acute coronary
  syndromes
• Prognosis via neurohormonal activation (BNP) are
  distinct from those of myocyte necrosis (TnI)
• BNP should be measured after an acute coronary
  syndrome in order to identify patients at high
  and low risk for adverse outcomes and that
  treatment, including the intensity of
  surveillance and the use of aggressive
  pharmacologic and interventional therapy, should
  be adjusted accordingly.

de Lemos JA, et al. N Engl J Med. 2001345.
59
Conclusions BNP as a Rapid Biomarker for CHF

• BNP testing should prove valuable in
• Diagnosis of patients with CHF
• Assessing severity of CHF disease
• Risk stratification of patients with ACS

60
Supplemental Slides
61
The Triage BNP Test

• The Triage MeterPlus
• Manufactured by Biosite Incorporated
• Runs individual Test Devices
• BNP
• Cardiac markers
• Drugs of abuse
• Results in approximately 15 minutes
• Built-in QC, QA functions
• Portable system

62
Hospitalization The Predominant Contributor to
CHF Costs
Total 38.1 billion (5.4 of total healthcare
costs)
OConnell JB, et al. J Heart Lung Transplant.
199413S107-S112.
63
Total Charges for CHF and Cardiogenic Shock DRG
127
Billions ()
1998 HCFA Quality of Care Surveillance.
64
Physiologic Effects of the RAAS and NPS
Adapted from Burnett JC. J Hypertens.
199917(Suppl 1)S37-S43.
65
BNP vs. NYHA Classification

12.3 95.4 221.5 459.1
1006.3 (pg/mL)
Triage BNP Test Package Insert.
66
BNP vs. Six-Minute Walk Study by Wieczorek et al
4
r0.513
3
2
Log BNP (pg/mL)
1
0
0
500
1000
1500
2000
2500
Distance (ft)
Wieczorek S, et al. Unpublished data.
67
Clinical Studies Using the Rapid, Point-of-Care
BNP Assay

• Use of BNP in the diagnosis of CHF in the
  emergency department
• Use of BNP as a screen for LV dysfunction in
  patients referred for echocardiography
• Use of BNP as it correlates to PAW pressure

68
Utility of B-Type Natriuretic Peptide in the
Diagnosis of Congestive Heart Failure in an
Urgent-Care Setting

• Dao Q, Krishnaswamy P, et al.
• Journal of the American College of Cardiology.
• Vol 37, No. 2, 2001.

69
BNP Levels in Patients With Dyspnea Secondary to
CHF or COPD
1076 138
86 39
N 56 N 94
Dao Q, et al. J Am Coll Cardiol. 200137.
70
BNP Levels in Patients With Edema Diagnosed With
CHF or Without CHF
1038 163
63 16
N 44 N 44
Dao Q, et al. J Am Coll Cardiol. 200137.
71
Multivariate Analysis With BNP Analyzed Last
Chi- Sens. Spec. Accuracy Variable Square
Significances () () ()
All 250 Cases History of CHF 89.01 0 62 93 80 Hear
t Size 31.96 0 77 91 85 Murmurs 19.24 0 77 91 85 P
ulm. Venous Hypertension 11.9 0.006 78 91 86 EKG-A
trial Fibrillation 9.06 0.0026 80 91 86 Pedal
Edema 9.96 0.0016 89 89 89 BNP 95.23 0 96 96 97 Ca
ses Without History of Pulm. Venous
Hypertension 32.48 0 41 97 84 Murmurs 26.48 0 76 8
7 84 Jugular Venous Distension 11.71 0.006 51 97 8
7 EKG-Atrial Fibrillation 12.54 0.0004 49 98 87 BN
P 55.27 0 95 100 98
Dao Q, et al. J Am Coll Cardiol. 200137.
72
ROC Curves for BNP and ED Diagnosis Using All
250 Patients
82
118
205
Sensitivity ()

---
BNP
--- ED diagnosis
AUC
0.884
0.9790


1-Specificity ()
Dao Q, et al. J Am Coll Cardiol. 200137.
73
BNP in LV Dysfunction
1077 272
567 113
391 89
63
N 105 N 53 N 42 N 14
Maisel A, et al. Am Heart J. 2001141.
74
Distribution of Patient Referral for
Echocardiography
Unknown LV function by history Normal LV function
by echo N 106 BNP 37 6
Unknown LV function by history Abnormal LV
function by echo N 94 BNP 492 75
Known LV dysfunction by history N 62 BNP
798 106
Maisel A, et al. Am Heart J. 2001141.
75
BNP Multinational Study
A Prospective, Blinded Trial of B-Type
Natriuretic Peptide as a Diagnostic Test for the
Emergency Diagnosis of Heart Failure
Rapid Measurement of B-Type Natriuretic Peptide
in the Emergency Diagnosis of Heart
Failure Maisel A, Krishnaswamy P, et al. The New
England Journal of Medicine. Vol. 347, No 3. July
18, 2002.
76
BNP Multinational Study Participating Centers

• Enrollment Centers
• University of California, San Diego Veterans
  Affairs Medical Center, San Diego, CA
• Henry Ford Hospital, Detroit, MI
• University of Pennsylvania, Philadelphia, PA
• Hospital Bichat, Paris, France
• Ulleval University Hospital, Oslo, Norway
• University of Cincinnati College of Medicine,
  Cincinnati, OH
• Hartford Hospital, Hartford, CN
• Analysis Support Centers
• University of Missouri-Kansas City School of
  Medicine, Truman Medical Center, Kansas City, MO
• University of Kentucky College of Medicine,
  Lexington, KY

77
Current Recommendations
The 2001 American College of Cardiology/American
Heart Association practice guidelines for the
evaluation and management of heart failure state
the role of blood B-type natriuretic peptide in
the identification of patients with CHF remains
to be fully clarified
Hunt SA, Baker DW, Chin MH, et al. ACC/AHA
Guidelines for the Evaluation and Management of
Chronic Heart Failure in the Adult Executive
Summary A Report of the American College of
Cardiology/American Heart Association Task Force
on Practice Guidelines (Committee to Revise the
1995 Guidelines for the Evaluation and Management
of Heart Failure). Circulation. 20011042996.
78
BNP Multinational Study Implications
The heart failure guidelines should incorporate
BNP in the clinical diagnosis of heart failure
79
Primary Endpoint
DIAGNOSTIC ACCURACY
Final Diagnosis Not CHF
Final Diagnosis CHF
Diagnostic Accuracy (a d) / (a b c d)
BNP gt Cutpoint Test Positive
a
b
d
BNP lt Cutpoint Test Negative
c
80
Statistical Considerations

• Primary endpoint was diagnostic accuracy
• Assumptions in the sample size calculation
• Diagnostic accuracy for the clinical evaluation
  85
• Prevalence of CHF 30
• Effect size of interest 5 absolute difference
  in diagnostic accuracy
• ? 0.20, ? 0.05 two-sided
• Calculated sample size was 1613
• Thus, this study had an 80 power to detect a 5
  absolute difference in diagnostic accuracy
  between the clinical evaluation and BNP for the
  final diagnosis of CHF versus not CHF

81
Baseline Characteristics
Characteristics
N 1586
Age
64 17
Gender male/female
56 / 44
Race white/black
49 / 43
History
CHF
33
MI
27
COPD
41
25
Diabetes
Signs
Elevated JVP
22
43
Rales
Wheezing
28
S3 Gallop
7
Murmurs
19
42
Edema
82
Final Diagnosis
N 1586
Not CHF 770
CHF 744
83
BNP vs. NYHA Functional Class
BNP Level (pg/mL)
I
II
III
IV
n 18
n 152
n 351
n 276
84
Congestive Heart Failure Diagnosis Nomogram
In Patients With 50 Probability - BNP Value of
1000 pg/mL - BNP Value of 20 pg/mL
McCullough P, et al. Circulation. 2002106.
85
BNP Diagnostic Utility by Race
BNP diagnostic utility is equivalent for blacks
and whites
AUC .89 (.87-.91) White .90 (.89-.93) Black
86
BNP Diagnostic Utility by Sex
Excellent diagnostic utility irrespective of
gender
AUC .92 (.90-.94) Male .87 (.84-.90) Female
87
BNP Combined With an ED Estimate
BNP improves clinical accuracy
AUC .86 (.84-.88) ED Estimate .90 (.88-.91)
BNP .93 (.92-.94) Combined
88
Study Endpoints
Sensitivity and Specificity
Final Diagnosis Not CHF
Final Diagnosis CHF
BNP gt Cutpoint Test Positive
a
b
d
BNP lt Cutpoint Test Negative
c
Sensitivity a / (a c)
Specificity d / (b d)
89
Study Endpoints
Predictive Value
Final Diagnosis Not CHF
Final Diagnosis CHF
Positive Predictive Value a / (a b)
BNP gt Cutpoint Test Positive
a
b
d
BNP lt Cutpoint Test Negative
c
Negative Predictive Value d / (c d)
90
Adjusted Odds Ratio 10-Month Mortality
de Lemos J, et al. N Engl J Med. 2001345.
91
Physiology of Natriuretic Peptides
Cardiac Overload
-

Urodilatin
ANPBNP
Neutral Endopeptidase Cytokines

Clearance
CNP
NPR-A
NPR-A/NPR-B
NPR-C
Decreased Vascular Growth
Decreased Blood Pressure
Increased Na/H20 Excretion
Adapted from Wilkins MR, et al. Lancet.
19973491307-1310.