Interpretation of BNP

1
Interpretation of BNP

• Peter A. McCullough, MD, MPH, FACC, FACPWilliam
  Beaumont Hospital, Royal Oak, MI

2
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

3
(No Transcript)
4
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

5
Natriuretic Peptides Storage and Secretion
Made Constitutively Briefly Stored in Granules
Stored Longer in Granules
Corin
Corin
120 min
3 min
20 min
Small Quantities in Blood
120 min
Adapted from McCullough PA, Omland T, Maisel AS.
B-type natriuretic peptides a diagnostic
breakthrough for clinicians. Rev Cardiovasc Med.
2003 Spring4(2)72-80.
6
Lifetime BNP/NT-proBNP Trajectory
5000
100
50
NT-ProBNP/BNP (pg/ml) Log Scale
20
30
60
90
Age (years)
McCullough PA, Sandberg KR. Sorting out the
Evidence on the Natriuretic Peptides, Rev
Cardiovasc Med, 2003, 4 (Suppl 4), S13-19
7
BNP Versus NT-proBNP
McCullough PA, Rev Cardiovasc Med. 2003.
8
Optimal Cutpoints for NT-proBNPDepend on Age and
Renal Function

• Package Insert lt75 yrs 125 pg/ml gt75 yrs 450
  pg/ml
• PRIDE Study, n600
• If lt 50 years and GFR gt 60 ml/min 450 pg/ml
• If gt 50 years and GFR gt 60 ml/min 900 pg/ml
• If at any age GFR lt 60 ml/min 1200 pg/ml

Januzzi, JL, in press, 2004. Anwaruddin S, et
al, in press 2005.
9
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

10
BNP and Body Weight in Normals
Framingham participants without CVD (N 3389)
25
Normal Overweight Obese
20
21.4
21.1
15
16.3
15.5
BNP (pg/mL)
13.1
12.7
10
5
0
Men
Women
Wang TJ et al. Circulation. 2004109594600.
11
Obesity and the Heart

• Fatty steatosis of myocardium
• Inflammatory factors
• Cytokines

Enhanced Clearance of BNP
Impaired Cardiac Production of BNP
12
BNP and Body Weight in Decompensated CHF Patients
McCord J, et al, Arch Int Med 2004
13
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

14
Estimated Glomerular Filtration and Normal Aging
McCullough PA. Beyond serum creatinine
defining the patient with renal insufficiency and
why? Rev Cardiovasc Med 20034(suppl 1)S2-S6.
NLM CIT. ID 12556731
15
Mean BNP by eGFR
P lt 0.0001 for all pairwise comparisons
McCullough PA, Duc P, Omland T, McCord J, Nowak
RM, Hollander JE, Herrmann HC, Steg PG, Westheim
A, Knudsen CW, Storrow AB, Abraham WT, Lamba S,
Wu AH, Perez A, Clopton P, Krishnaswamy P,
Kazanegra R, Maisel AS Breathing Not Properly
Multinational Study Investigators. B-type
natriuretic peptide and renal function in the
diagnosis of heart failure an analysis from the
Breathing Not Properly Multinational Study. Am J
Kidney Dis. 2003 Mar41(3)571-9. NLM CIT. ID
12612980
16
Optimal Cutpoints for Biosite BNP by Renal
Function
eGFR(ml/min/1.73 m2) 90 8960
5930 lt30 N
540 480 358
74 Creatinine (mg/dL) 0.7
1.0 1.5 2.9 Optimum
Cutpoint (pg/mL) 70.7 104.3
201.2 225.0 AUC 0.91
0.90 0.81 0.86
eGFR estimated glomerular filtration rate
CrCl
McCullough PA, Duc P, Omland T, McCord J, Nowak
RM, Hollander JE, Herrmann HC, Steg PG, Westheim
A, Knudsen CW, Storrow AB, Abraham WT, Lamba S,
Wu AH, Perez A, Clopton P, Krishnaswamy P,
Kazanegra R, Maisel AS Breathing Not Properly
Multinational Study Investigators. B-type
natriuretic peptide and renal function in the
diagnosis of heart failure an analysis from the
Breathing Not Properly Multinational Study. Am J
Kidney Dis. 2003 Mar41(3)571-9. NLM CIT. ID
12612980
17
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

18
BNP levels in stable patients with diastolic
dysfunction
BNP (pg/ml)
Lubien R, et al, Utility of B-natriuretic peptide
in detecting diastolic dysfunction comparison
with Doppler velocity recordings. Circulation
2002 Feb 5105(5)595-601
19
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

20
ACS Survival by BNP Quartile Analysis
10
Quartile 4 (BNP gt 80 pg/ml)
8
6
Quartile 3
Mortality, Percent
4
Quartile 2
2
Quartile 1
0
0
50
100
150
200
250
300
Time (days)
Braunwald, N Engl J Med, Vol 345, No. 14, 2001
21
Kaplan-Meier Survival Curves Regarding
Probability of Death During 1 Year for Patient
Strata, According to Quartiles of NT-proBNP
Plt0.001, log rank
gt1869 ng/L
Cumulative Probability of Death
669-1869 ng/L
238-669 ng/L
lt237 ng/L
Days
James S. et al., Circulation 2003 108275-81.
22
Mortality at 1-Year Follow-Up Among Strata of
Patients, According to Quartiles of NT-proBNP
and Quartiles of Creatinine Clearance
Death 1 year,
NT-proBNP, quartiles pg/mL
gt1869
669-1869
238-668
lt237
Creatinine clearance, ml/min
James S. et al., Circulation 2003 108275-81.
23
Outline

• Differentiating BNP and NT ProBNP
• Nuances of BNP Testing
• Obese patients and BNP Interpretation
• BNP and Cardiorenal Syndrome
• BNP in Preserved Systolic Dysfunction
• BNP in ACS
• BNP and Nesiritide Treatment

24
Blood Levels of BNP and NT-proBNP with Nesiritide
Infusion
N27 with CHF
Fitzgerald, et al, J Card Fail, October 2004
10(4, Supplement) (Abstract 129)
25
Conclusions

• BNP and NT-proBNP have fundamental differences
• Adiposity ? BNP 30-50
• Renal insufficiency ? BNP 100-500 pg/ml range
• BNP in diastolic dysfunction
• Elevated but not as high as systolic dysfunction
• Related to severity of diastolic impairment
• BNP in ACS
• Elevated in only 25 of UA or ACS
• Is a risk marker for mortality
• BNP is dynamic through a nesiritide infusion