The prognostic value of N-terminal pro-B-type natriuretic peptide for death and cardiovascular events in healthy normal and stage A/B heart failure subjects.
OBJECTIVE
Our objective was to determine the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors for heart failure (HF), which we term healthy normal.


BACKGROUND
Previous studies report that plasma NT-proBNP has prognostic value for cardiovascular events in the general population even in the absence of HF. It is unclear if NT-proBNP retains predictive value in healthy normal subjects.


METHODS
We identified a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent echocardiography and NT-proBNP measurement. We further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. Healthy normal was defined as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. Subjects were followed for death, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively.


RESULTS
NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of death, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities.


CONCLUSIONS
These findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects and have important implications for NT-proBNP-based strategies for early detection and primary prevention of cardiovascular disease.
McKie
Paul M
PM
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. mckie.paul@mayo.edu
Cataliotti
Alessandro
A
Lahr
Brian D
BD
Martin
Fernando L
FL
Redfield
Margaret M
MM
Bailey
Kent R
KR
Rodeheffer
Richard J
RJ
Burnett
John C
JC
D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D015150:Echocardiography, Doppler; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
J Am Coll Cardiol. 2002 Sep 4;40(5):976-82
12225726
Stat Med. 2004 Jul 15;23(13):2109-23
15211606
J Am Coll Cardiol. 2006 Jan 17;47(2):345-53
16412859
J Am Coll Cardiol. 1997 Jul;30(1):8-18
9207615
J Am Coll Cardiol. 2004 Mar 17;43(6):1019-26
15028361
JAMA. 2003 Jan 8;289(2):194-202
12517230
Am J Cardiol. 1987 Apr 15;59(9):956-60
2952002
JAMA. 2005 Apr 6;293(13):1609-16
15811980
Eur J Heart Fail. 2004 Mar 15;6(3):365-8
14987590
Eur Heart J. 2006 Feb;27(3):330-7
16293638
N Engl J Med. 2004 Feb 12;350(7):655-63
14960742
Am J Med. 2008 Jan;121(1):50-7
18187073
Circulation. 1998 Nov 24;98(21):2282-9
9826315
N Engl J Med. 2002 Jul 18;347(3):161-7
12124404
Ann Epidemiol. 2004 Sep;14(8):579-84
15350958
Stat Med. 2008 Jan 30;27(2):157-72; discussion 207-12
17569110
Eur Heart J. 2009 Jan;30(1):66-73
19029123
Mayo Clin Proc. 2011 Mar;86(3):210-8
21364112
Circulation. 2002 Jul 23;106(4):416-22
12135939
Hypertension. 2006 May;47(5):874-80
16585413
Hum Mol Genet. 2007 Jun 1;16(11):1343-50
17412758
JAMA. 2007 Jan 10;297(2):169-76
17213400
J Am Coll Cardiol. 2009 Apr 14;53(15):e1-e90
19358937
Am J Cardiol. 1986 Feb 15;57(6):450-8
2936235
J Am Coll Cardiol. 2003 Mar 19;41(6):1036-43
12651054
Clin Chem. 2005 Feb;51(2):445-7
15681561
CMAJ. 2006 Sep 12;175(6):611-7
16966666
N Engl J Med. 2008 Sep 4;359(10):1018-26
18768945
Circulation. 2007 Mar 27;115(12):1563-70
17353436